Media Clips - EMBL

ENCODE Nature Publicaiton
Selected Media and Web Clippings
6/13 to 6/18, 2007
BBC News “Genome Further Unraveled”
Financial Times “Research Reveals Complexity in How Human Genes Interact
The Guardian “Study Shines New Light on Genome”
The Times “DNA Analysis Provides New Insight into the Roots of Our Illnesses”
The Glasgow Herald “Genome ‘Junk’ May Be Key To How We Work”
Business Weekly “’Parts List’ Could Reshape Genome Understanding”
New Scientist “’Junk’ DNA Make Compulsive Reading”
Nature “Genome Project Turn Up Evolutionary Surprises”
The Economist “Really New Advances”
ABC News “Landmark Genome Study Shows Complexity of Human ‘Code’”
Bloomberg “’Junk’ Isn’t Junk”
Boston Globe “DNA Study Challenges Basic Idea of Genetics”
Boston Globe “Science: Miracles and Mysteries”
CBS News “DNA Decoding Landmark”
PBS Newshour “’Landmark’ Study Changes Long-Held DNA Beliefs”
Reuters “Human Instruction Book Not So Simple;Studies”
Washington Post “Human Genome Yields Up More Secrets”
Washington Post “Intricate Toiling Found in Nooks of DNA…”
Washington Post Graphic from article above”
WebMD “Genetics Revolution Arrives”
Scientific American “The 1 Percent Genome Solution”
The Scientist “First Pages of Regulation ‘Encyclopedia’”
Science “DNA Study Forces Rethink of What It Means to Be a Gene”
Wired “Your Genome is Really, Really, REALLY Complicated”
National Public Radio “Reading between the Genomes”
Ars Technica “ENCODE Finds the Human Genome to Be an Active Place”
Chemical and Eng. News “Finding Function in the Genome”
GenomeWeb “Human Genome Not So Tidy After All, ENCODE Project Suggests”
Toronto Star “DNA ‘Junk’ Appears to Have Uses”
Agence France Presse “Landmark Study Prompts Rethink of Genetic Code”
La Republlica “Svolta Nello Studio…”
El Mundo “Un Nuevo ‘Manuel de Instrucciones’ del genoma…”
Foha de Sao Paulo “A Biologie Acaba…”
Frankfurter Neue Presse “Grammatik der Gene Viel Komplexer als Gedacht“
Belgium Cordis News “New Research Challenges Understanding of Human Genome”
Xinhua News Agency Untitled

BBC NEWS | Science/Nature | Human genome further unravelled
Human genome further unravelled
A close-up view of the human genome has revealed its innermost workings to be far
more complex than first thought.
The study, which was carried out on just 1% of our DNA code, challenges the view that genes
are the main players in driving our biochemistry.
Instead, it suggests genes, so called junk DNA and other elements, together weave an intricate
control network.
The work, published in the journals Nature and Genome Research, is to be scaled up to the rest
of the genome.
Views transformed
The Encyclopaedia of DNA Elements (Encode) study was a collaborative effort between 80
organisations from around the world.
It has been described as the next step on from the Human Genome Project, which provided the
sequence for all of the DNA that makes up the human species' biochemical "book of life".
We are now seeing the majority of the rest of the
genome is active to some extent
Tim Hubbard, Sanger Institute
Ewan Birney, from the European Molecular Biology Laboratory's European Bioinformatics
Institute, led Encode's analysis effort. He told the BBC: "The Human Genome Project gave us the
letters of the genome, but not a great deal of understanding. The Encode project tries to
understand the genome."
The researchers focussed on 1% of the human genome sequence, carrying out 80 different types
of experiments that generated more than 600 million data points.
The surprising results, explained Tim Hubbard from the Wellcome Trust Sanger Institute,
"transform our view of the genome fabric".
THE DNA MOLECULE
The double-stranded DNA molecule - wound in a helix - is
held together by four chemical components called bases
Adenine (A) bonds with thymine (T); cytosine(C) bonds
with guanine (G)
Groupings of these "letters" form the "code of life"; a code
that is very nearly universal to all Earth's organisms
Written in the DNA are genes which cells use as starting
http://newsvote.bbc.co.uk/mpapps/pagetools/print/news.bbc.co.uk/1/hi/sci/tech/67...
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6/14/2007

BBC NEWS | Science/Nature | Human genome further unravelled
Previously, genome activity was thought of in terms of the 22,000 genes that make proteins -
the functional building blocks in our cells - along with patches of DNA that control, or regulate,
the genes.
The other 97% or so of the genome was said to be made up of "junk" DNA - so called because it
had no known biological function.
However, junk DNA may soon need a new moniker.
Dr Hubbard said: "We are now seeing the majority of the rest of the genome is active to some
extent."
He explained that the study had found junk DNA was being transcribed, or copied, into RNA - an
active molecule that relays information from DNA to the cellular machinery.
He added: "This is a remarkable finding, since most prior research suggested only a fraction of
the genome was transcribed."
'Complex picture'
templates to make proteins; these sophisticated molecules
build and maintain our bodies
Dr Birney added that many of the RNA molecules were copying overlapping sequences of DNA.
He said: "The genome looks like it is far more of a network of RNA transcripts that are all
collaborating together. Some go off and make proteins; [and] quite a few, although we know
they are there, we really do not have a good understanding of what they do.
"This leads to a much more complex picture."
The researchers now hope to scale up their efforts to look at the other 99% of the genome.
By finding out more about its workings, scientists hope to have a better understanding of the
mechanics of certain diseases.
Dr Birney said that in the future, they would hope to combine their findings with some of the
larger studies that are currently investigating genes known to be associated with particular
conditions.
He added: "As we understand these things better, we get better insight into disease, and when
we get better insight into disease, we get better insight into diagnosis and the chances to create
new drugs."
Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/1/hi/sci/tech/6749213.stm
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6/14/2007

FT.com print article
Research reveals complexity in how human genes
interact
By Clive Cookson in London
Published: June 14 2007 03:00 | Last updated: June 14 2007 03:00
The first thorough examination of how the human genome works, published today, has overthrown
the traditional view of our genetic blueprint as a collection of independent genes floating in an
ocean of "junk DNA".
Instead, the 3bn chemical "letters" of the human genetic blueprint form an extremely complex
network in which genes, regulatory elements and other DNA sequences interact in overlapping
ways that are not yet understood.
The new view of the genome appears in 29 scientific papers published simultaneously in the
journals Nature and Genome Research. It comes from a $42m (€31m, £23m) international project
called the Encyclopedia of DNA elements (Encode) consortium, led by the US National Human
Genome Research Institute with the Wellcome Trust and the European Bioinformatics Institute.
Francis Collins, NHGRI director, called the results"a landmark in molecular biology". He said: "This
impressive effort has uncovered many exciting surprises and blazed the way for future efforts to
explore the functional landscape of the entire human genome."
Conventional genes - stretches of DNA coding for proteins, the molecules that do almost all the
biochemical work in living creatures - make up only 2 per cent of the human genome. Even with the
separate control and regulatory regions of the genome that are responsible for switching
conventional genes on and off, no more than 10 per cent of human DNA is made of such clear-cut
functional elements. Until now, many biologists have regarded the majority of the genome as "junk
DNA" carried from generation to generation but with no biological function.
The Encode project analysed in great depth a representative 1 per cent of the genome (30m letters
of DNA). This showed that most human DNA is biologically active, rather than being pure junk
DNA.
The purpose of all this transcribed genomic information remains unclear. Some of it represents a
more sophisticated control system for conventional genes; the new work identifies many previously
unknown regulatory regions and shows that control regions may be in quite different areas of the
genome from the genes they affect. This could complicate efforts to treat diseases.
Other parts of the genome may represent a previously unsuspected evolutionary reserve - not
doing much at the moment but potentially useful for the future.
Dr Collins provided an analogy: "It is like the clutter in the attic of your house, which you don't get
rid of, in case you ever need it," he said.
"Most of the time, the genome is acting on the first and second floors but over evolutionary time
[millions of years] theclutter in the attic may be useful."
Comparisons show that many of these regions are not shared with other species but are restricted
to the human genome - a potential source of new variation.
Copyright The Financial Times Limited 2007
BUSINESS LIFE
SCIENCE & ENVIRONMENT
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6/14/2007

Education | Study shines new light on genome
Study shines new light on genome
· Most intensive study ever of our genetic code · So-called junk DNA found to play highly active
role
Ian Sample, science correspondent
Thursday June 14, 2007
Guardian
Scientists have been forced to rethink how the human genome turns a single cell into a complex living being
following the most intensive study of our genetic code ever undertaken.
The research reveals that genes make up only a tiny fraction of the role played by the 3bn letters that constitute
the entirety of the human genome.
Large swaths of the genome, previously dismissed as "junk DNA" because it was thought to serve no practical
purpose, have been found to be highly active inside the cells in our bodies. Other sequences of genetic code are
thought to be "on standby", awaiting a time further down the evolutionary path when they will be beneficial to
human beings.
The scientists claim the findings will have a dramatic impact on their ability to pinpoint how genetic defects trigger
diseases. Instead of simply looking for mutations in individual genes, it is certain that defects in other parts of the
genome will contribute to complex conditions, among them diabetes and coronary heart disease.
The results, published in Nature today, are the culmination of a $42m, five-year project called ENCODE
(ENCyclopaedia Of DNA Elements) involving 80 different scientific teams in 11 countries.
Page 1 of 1
The project set out to examine the human genome in unprecedented detail, to work out every different way in
which the genetic building blocks, represented by the letters G, T, A and C, work within the body.
The scientists found that beyond genes lay a multitude of other jobs being done by sequences of DNA. Much of
the genetic material is transcribed into molecules that relay information from the genome to the biological
machinery of our cells.
"If you think of the letters that make up the human genome as the alphabet, then you can think of genes as the
verbs. With this project we're identifying all of the other grammatical elements and the syntax of the language we
need to read the genetic code completely," said Manolis Dermitzakis, a scientist on the ENCODE project at the
Wellcome Trust Sanger Institute in Cambridge.
The findings highlighted how scientists had become so blinded by the importance of genes that the role of other
parts of the genome had largely gone unappreciated, he said.
In the pilot study, the researchers focused on 1% of the human genome, or 3bn letters, which were chosen to
represent the entire human genetic code. They aim to examine the rest of the genome over the next four years,
streamlining the process to complete it for less than $100m.
By understanding how every letter of the human genome functions in the body, scientists believe they will be able
to learn how complex diseases are caused by genetic glitches that build up throughout the genome.
EducationGuardian.co.uk © Guardian News and Media Limited 2007
http://education.guardian.co.uk/print/0,,330023986-108233,00.html
6/14/2007

Printer Friendly
From The Times
June 14, 2007
DNA analysis provides new insight into the
roots of our illnesses
Mark Henderson, Science Editor
A new understanding of how DNA shapes our health and makes us human has emerged from the most
exhaustive analysis yet of the workings of the human genome.
The first “parts list” of genetic elements that are biologically active in the body has revealed that DNA
functions in a much more complex fashion than was once assumed, offering insights into the inherited roots
of diseases such as diabetes and cancer.
The work of the Encode Consortium — the acronym stands for Encyclopedia of DNA Elements — also
sheds important light on the genetic differences that separate humans from chimpanzees and other
species.
While the human genome is made up of approximately three billion DNA “letters”, only about 3 per cent of
these are known to contribute to 22,000 or so genes — DNA “sentences” containing instructions for making
proteins that control the body’s chemical reactions. Most of the remaining 97 per cent has traditionally been
thought of as “junk DNA”, which appeared to be an evolutionary relic that performed no tasks of
significance.
The new research shows that much of this junk DNA is not redundant but is chemically active in ways that
influence how genes are switched on and off.
Mutations in these regulatory genetic regions are thus likely to explain some of our varying susceptibility to
disease — some have already been linked to type 2 diabetes and prostate and colon tumours.
While the bulk of our genes are shared with other organisms, much more of our junk DNA is peculiar to our
species: 99 per cent of human and chimpanzee genes are identical compared with only 96 per cent of all
DNA. As there is more variation in the junk, this could influence traits such as intelligence and language.
Ewan Birney, of the European Bioinformatics Institute, near Cambridge, who led the analysis, said: “Our
data certainly agree with the idea that many of the differences between mammals lie in this junk DNA. We
now have a much better idea of what most of our DNA might actually be doing. That is also going to help us
to characterise what is going on in disease.”
Francis Collins, director of the US National Human Genome Research Institute, which funded the project,
said: “This impressive effort has uncovered many exciting surprises and blazed the way for future efforts to
explore the functional landscape of the entire human genome.”
The consortium, which pub-lishes its results today in Nature and Genome Research, set out to examine
what every bit of DNA does by looking in detail at 30 million letters or base pairs — 1 per cent of the
genome.
Page 1 of 2
About 3 per cent of the DNA — the genes — was found to be transcribed into the signalling molecule RNA
and then to make proteins. Another 6 per cent hitherto regarded as junk, however, was unexpectedly found
to be written into RNA without producing proteins. It is this part of the genome that appears to play a critical
regulatory role, controlling when genes are active or silent.
http://www.timesonline.co.uk/tol/news/uk/science/article1929099.ece?print=yes
6/14/2007

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Some of this active DNA outside genes, however, appears to make RNA without affecting the functions of
cells — it is chemically alive but neutral. While scientists do not yet know what proportion is neutral, or why,
one theory is that it provides a stock of genetic material from which potentially useful mutations can arise to
drive evolution.
“It may be a kind of warehouse for natural selection,” Dr Birney said. “Evolution seems to have kept this
around for a reason, to somehow set itself up for the future. It is a bit like Pop Idol— if you throw the net
widely, you can pick up talent when it appears.”
The Encode team is working to scale up the project to cover the entire human genome.
Page 2 of 2
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6/14/2007

Printer Friendly Format - The Herald
Genome ‘junk’ may be key to how we work
The human genetic code is far more complex and dynamic than
scientists had previously imagined, a study by experts from around
the world has found.
It was previously assumed only certain stretches of DNA, the genes,
had any important function. However, the study shows most of the
genome, including parts dismissed as "junk", appears to be actively
involved in relaying instructions to cells within the body.
Instead of a desert containing occasional oases, scientists now see
the genome as an intricate tapestry of interwoven connections.
Dr Tim Hubbard, from the Wellcome Trust Sanger Institute in Hinxton,
Cambridge-shire, who took part in the research, said: "The majority of
the genome is copied, or transcribed, into RNA, the active molecule
in our cells.
"This is a remarkable finding, since most prior research suggested
only a fraction of the genome was transcribed."
Scientists had already learned areas of DNA outside the genes were
involved in gene regulation but the new work identifies previously
unknown control regions.
"The integrated approach has helped us to identify new regions of
gene regulation and altered our view of how it occurs," said Dr
Hubbard.
The ENCODE (ENCyclopaedia Of DNA Elements) project involved
scientists from 80 centres and took five years.
Dr Manolis Dermitzakis, another member of the Sanger Centre team,
said: "A major surprise was that many of the novel control regions are
not shared with other species. We appear to have a reservoir of
active elements that seem to provide no specific or direct benefit.
"Our suggestion is these elements can provide a source for new
variation between species and within the human genome. This is our
genomic seedcorn for the future."
12:11am Thursday 14th June 2007
By JAMES MORGAN reporter
http://www.theherald.co.uk/misc/print.php?artid=1470047
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6/15/2007

‘PARTS LIST’ COULD RESHAPE GENOME UNDERSTANDING
By Business Weekly, 14 June 2007
An exhaustive four-year international effort to build a ‘parts list’ of all
biologically functional elements in one per cent of the human genome is
promising to reshape our understanding of how the human genome
functions, challenging the traditional view of a genetic blueprint as a tidy
collection of independent genes.
courtesy: EMBL photolab.
Ewan Birney, head of genome annotation at EMBL-EBI Picture
The repercussions of the findings could potentially affect views and processes in a wide range of
areas stretching from evolution to human disease.
The project, which will serve as a pilot to test the feasibility of a full-scale initiative to produce a
comprehensive catalogue of all components of the human genome crucial for biological function,
found that there exists a network in which genes, regulatory elements and other types of DNA
sequences interact in complex, overlapping ways.
Led by the European Molecular Biology Laboratory’s European Bioinformatics Institute (EMBL-EBI) in
Hinxton, Cambridge, the ENCyclopedia Of DNA Elements – ENCODE – drew on expertise from 35
groups from 80 organisations around the world.
Major findings include the discovery that the majority of human DNA is transcribed into RNA and
that these transcripts extensively overlap, challenging the long-standing view that the human
genome consists of a small set of discrete genes, along with a vast amount of ‘junk’ DNA that is not
biologically active.

(article continues after advertisement)
The new data indicate that the genome contains very little unused sequences; genes are just one of
many types of DNA sequences that have a functional impact.
The consortium identified many previously unrecognised start sites for transcription and new
regulatory sequences that contrary to traditional views are located not only upstream but also
downstream of transcription start sites.
“Our results reveal important principles about the organisation of functional elements in the human
genome, providing new persp-ectives on everything from DNA transcription to mammalian
evolution,” said Ewan Birney, head of genome annotation at EMBL-EBI.
Until recently, researchers had thought that most DNA sequences with important biological function
would be constrained by evolution making them likely to be conserved as species evolve.
But about half of the functional elements in the human genome do not appear to have been
constrained during evolution, suggesting that many species’ genomes contain a pool of functional
elements that provide no specific benefits in terms of survival or reproduction.
Over the next couple of years the ENCODE project will be scaled up to the entire genome. The
Ensembl project, a joint EMBL-EBI and Sanger Institute project, jointly headed by Ewan Birney, has
already generated some initial genome wide datasets with early full scale datasets. This integration
has led to the identification of just over 110,000 regulatory elements across the human genome.

'Junk' DNA makes compulsive reading - life - 13 June 2007 - Print Article - New ...
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'Junk' DNA makes compulsive reading
13 June 2007
NewScientist.com news service
Andy Coghlan
The central dogma of genetics could hardly be simpler: DNA makes RNA
makes protein. Except that now this tidy picture of how genes work has
been muddied by a mammoth investigation of human DNA.
It turns out that DNA generates far more RNA than the standard dogma
predicts it should - even some "junk" DNA gets transcribed. The
Encyclopedia of DNA Elements (ENCODE) project has quantified RNA
transcription patterns and found that while the "standard" RNA copy of a
gene gets translated into a protein as expected, for each copy of a gene
cells also make RNA copies of many other sections of DNA. None of the
extra RNA fragments gets translated into proteins, so the race is on to
discover just what their function is.
"One of the critical questions is whether
they're important or not, and we simply don't
know," says Ewan Birney, head of genome
annotation at the European Bioinformatics
Institute in Cambridge, UK, and analysis
coordinator for the ENCODE project, which
involves many labs from around the world.
Birney says that while the central dogma still
holds, the discovery of so much extra RNA
could mean there are hitherto unrecognised
subtleties of gene regulation that now need to
be explained. "It's no longer the neat and tidy
genome we thought we had," says John
Greally of the Albert Einstein College of
Medicine in New York City.
Enlarge image
A role for junk
Click to Print
ENCODE labs analysed 30 million bases or
"letters" of human DNA - about 1 per cent of
the total - covering 44 different and randomly
chosen sites in our genome, and measured the associated RNA transcription in living cells. The whole
sample was analysed independently by a range of methods in 38 labs, then cross-checked.
With around 400 known genes in the chosen sample, researchers expected an equal number of
different RNA transcripts according to the central dogma of one RNA copy per gene. Instead, they
found about twice the predicted quantity of RNA transcripts. Moreover, they also found almost 10
times the expected number of gene switches - the points in DNA where transcription can be activated
(Nature, vol 447, p 799).
Many of the RNA transcripts were copies of sections lying across genes and their adjacent stretches
of "junk" DNA (see Diagram). Even more surprising, many transcripts were copies of junk DNA
situated further from genes. The researchers speculate that the unexpected glut of gene switches
might explain the extra RNA.
Birney says that the additional switches may be mutations that appear by accident and then generate
new slugs of RNA, but because they are produced randomly, most are evolutionarily neutral
"passengers" in the genome. There might be rare occasions, however, when a new RNA does confer
an advantage.
Tom Gingeras of genomics firm Affymetrix in Santa Clara, California, and a co-leader of ENCODE,
disagrees. He first reported transcription of non-coding DNA three years ago (New Scientist, 21
February 2004, p 10), and is convinced that the extra RNAs have a function, perhaps to help transport
molecules around the cell or fine-tune and modulate the activity of genes themselves. "We don't think
http://www.newscientist.com/article.ns?id=mg19426086.000&print=true
Page 1 of 2
6/13/2007

'Junk' DNA makes compulsive reading - life - 13 June 2007 - Print Article - New ...
they're produced by accident," he says.
Whatever the truth, the results pose fresh puzzles about how genes work. "It would now take a very
brave person to call non-coding DNA junk," says Greally.
From issue 2608 of New Scientist magazine, 13 June 2007, page 20
Close this window
Printed on Wed Jun 13 21:43:30 BST 2007
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6/13/2007

Genome project turns up evolutionary surprises
Nature
Published online: 13 June 2007; | doi:10.1038/447760a
Genome project turns up evolutionary surprises
Findings reveal how DNA is conserved across animals
Erika Check
Close window
The latest studies of the instructions embedded in the human genome are revealing how
evolution has shaped our species.
In 'Identification and analysis of functional elements in 1% of the human genome by the
ENCODE pilot project' 1, 2 , and in a themed issue of Genome Research 3 , scientists report the
first findings from a project called ENCODE. This 'encyclopedia of DNA elements' attempts to
discover how our cells make sense of the DNA sequence in the human genome. Already,
ENCODE is up-ending one piece of conventional scientific wisdom: the idea that biologically
relevant DNA resists change over evolutionary time.
ENCODE aims to catalogue all the "functional elements" in the genome — the DNA sequences
that control how and when our cells use our genes. Most of these controls seem to be written
into so-called non-coding DNA, which does not make a detectable protein product. Because
organisms depend on functional elements working correctly, scientists have long thought that
such elements should not change much over evolutionary time. So researchers have mostly
looked for key functional elements in non-coding DNA that is the same across species, known
as conserved or constrained DNA.
The ENCODE project aims to catalogue all the 'functional elements' in the
human genome.
ARCTIC-IMAGES/CORBIS
But ENCODE is the first project to compare long stretches of non-coding DNA across many
mammals, from mice to monkeys to humans. This comparison suggests that evolutionary
http://www.nature.com/news/2007/070611/pf/447760a_pf.html
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6/13/2007

Genome project turns up evolutionary surprises
processes don't always freeze functional DNA in place.
Page 2 of 3
"The fact that we found so much functional sequence that did not seem to be evolutionarily
constrained across all mammals is really surprising," says Elliott Margulies of the National
Human Genome Research Institute in Bethesda, Maryland, who co-chaired one of the ENCODE
analysis groups.
The finding comes from the ENCODE pilot project, which used multiple methods to collect and
analyse data on just 1% of the human genome — not an easy task (see 'Scaling up to a
monumental task'). In one part of the project, groups of experimental biologists used a suite
of laboratory techniques to find out what portions of the genome might be functional.
Meanwhile, groups of computational biologists compared the ENCODE sequences across
humans and 28 other animals to find constrained regions of DNA that had changed little
throughout evolution.
But when the different groups compared their results, they found that their predictions about
key portions of the genome didn't always agree: the biologists' list of functional sequences
didn't match the computational group's list of constrained sequences.
At first, many were sceptical of this result, says John Stamatoyannopoulos of the University of
Washington in Seattle, a co-chair of one of the ENCODE analysis groups. "It raised some
eyebrows," he says. "But eventually all the ENCODE groups started coming out with the same
thing." Overall, biologists found no evidence of function for about 40% of the constrained
ENCODE regions. On the flipside, about half of the functional elements found in non-coding
DNA were totally unconstrained.
The finding that many constrained regions weren't considered to be functional is not too
surprising, because it is unlikely that ENCODE included enough tests on enough different types
of cells to capture every major aspect of biology. But the idea that important DNA might also
be unstable is newer, and intriguing, because it undermines the assumption that biological
function requires evolutionary constraint.
"We're generalizing this principle over mammals, and over many functional elements," says
Ewan Birney, head of genome annotation at the European Bioinformatics Institute in
Cambridge, UK, and a leader of ENCODE. "We're coming out quite strongly that this is not
merely a curiosity of our genome — it's a really important part of the way our genome works."
But how can major components of the mammalian genome change essentially randomly over
time? That is not entirely clear. The authors of the ENCODE paper speculate that the
unconstrained genomic regions are evolving "neutrally" — that is, they are constantly changing
in ways that are neither good nor bad for the individual. This means that, on the whole, many
genetic changes simply don't affect overall biology.
This has major consequences for understanding the relationship between genetics and biology,
Birney says. "It means, for example, that if you look at some conserved piece of biology —
say, how the kidneys work in mice and humans — not all of those bits of biology will be
conserved or constrained at the level of the DNA bases, and that's quite a strong shift."
But not everyone agrees with that take. For example, John Mattick at the University of
Queensland in Brisbane, Australia, argues that the widely accepted calculation of the baseline,
or neutral, rate of mammalian evolution is flawed. Because measurements of constraint rely on
a comparison with the neutral rate, it is possible that many of ENCODE's so-called
unconstrained regions really aren't unconstrained, Mattick argues.
"I would have said that this finding suggests that many regions of our genome are evolving
http://www.nature.com/news/2007/070611/pf/447760a_pf.html
6/13/2007

Genome project turns up evolutionary surprises
under weak selection pressure, or that our measurements of the neutral rate of evolution are
incorrect," says Mattick, who is an author on the ENCODE paper.
In fact, Mattick thinks scientists are vastly underestimating how much of the genome is
functional. He and Birney have placed a bet on the question. Mattick thinks at least 20% of
possible functional elements in our genome will eventually be proven useful. Birney thinks
fewer are functional. The loser will buy the winner a case of the beverage of his choice.
Meanwhile, other scientists are gathering data to answer new questions raised by ENCODE.
Many hope that other ongoing studies, such as comparable genome sequences from additional
primate species, will help decide which parts of the ENCODE data to study first.
Article brought to you by: Nature
References
1. The ENCODE Project Consortium Nature 447, 799–816 (2007). | Article |
2. Greally, J. M. Nature 447, 782–783 (2007). | Article |
3. Genome Res. 17, Issue 6 (2007).
4. Nature 447, 361 (2007). | Article |
Story from news@nature.com:
http://news.nature.com//news/2007/070611/447760a.html
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6/13/2007

Economist.com
RNA
Really New Advances
Jun 14th 2007
From The Economist print edition
Page 1 of 5
Molecular biology is undergoing its biggest shake-up in 50 years, as a hitherto littleregarded
chemical called RNA acquires an unsuspected significance
IT IS beginning to dawn on biologists that they may have got it wrong. Not completely wrong, but
wrong enough to be embarrassing. For half a century their subject had been built around the
relation between two sorts of chemical. Proteins, in the form of enzymes, hormones and so on,
made things happen. DNA, in the form of genes, contained the instructions for making proteins.
Other molecules were involved, of course. Sugars and fats were abundant (too abundant, in some
people). And various vitamins and minerals made an appearance, as well. Oh, and there was also
a curious chemical called RNA, which looked a bit like DNA but wasn't. It obediently carried genetic
information from DNA in the nucleus to the places in the cell where proteins are made, rounded up
the amino-acid units out of which those proteins are constructed, and was found in the protein
factories themselves.
All that was worked out decades ago. Since then, RNA has been more or less neglected as a
humble carrier of messages and fetcher of building materials. This account of the cell was so
satisfying to biologists that few bothered to look beyond it. But they are looking now. For,
suddenly, cells seem to be full of RNA doing who-knows-what.
And the diversity is staggering. There are scnRNAs, snRNAs and snoRNAs. There are rasiRNAs,
tasiRNAs and natsiRNAs. The piRNAs, which were discovered last summer, are abundant in
developing sex cells. No male mammal, nor male fish, nor fly of either sex, would be fertile
without them. Another RNA, called XIST, has the power to turn off an entire chromosome. It does
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so in females because they, unlike males, have two X chromosomes and would otherwise get an
unhealthy double dose of many proteins. There is even a “pregnancy-induced non-coding RNA”,
cutely termed PINC. New RNAs are rushing forth from laboratories so rapidly that a group called
the RNA Ontology Consortium has been promised half a million dollars to prune and tend the
growing thicket of RNA-tailed acronyms.
In the light of this abundance, perceptions about what a gene is need to change. Genes were once
thought of almost exclusively as repositories of information about how to build proteins. Now, they
need to be seen for what they really are: RNA factories. Genes for proteins may even be in the
minority. In a human, the number of different microRNAs, one of the commonest of the newly
discovered sorts of RNA, may be as high as 37,000 according to Isidore Rigoutsos, IBM's genomeminer
in chief. That compares with the 21,000 or so protein-encoding genes that people have.
Philosophers of science love this sort of thing. They refer to it as a paradigm shift. Living through
such a shift is confusing for the scientists involved, and this one is no exception. But when it is
over, it is likely to have changed people's views about how cells regulate themselves, how life
becomes more complex, how certain mysterious diseases develop and even how the process of
evolution operates. As a bonus, it also opens up avenues to develop new drugs.
Increase and multiply
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Not everyone agrees with Dr Rigoutsos about how many microRNAs there are. But the results of a
project called the Encyclopaedia of DNA Elements (ENCODE), published in this week's Nature,
suggest he is on the right track. The project looked in detail at 1% of the human genome. When
ENCODE started, four years ago, the conventional wisdom was that only a few percent of this 1%,
corresponding mainly to the protein-coding genes, would actually be transcribed into RNA. In fact,
most of it is. What this means is unclear—just how unclear being shown by the fact that although
the consortium was willing to identify only eight places where this transcription definitely results in
an RNA molecule with a job other than passively carrying the code for a protein, they found
another 268 where there was likely to be one, and several thousand more where the data hinted
there might be one. That compares with 487 protein-coding genes in the same sequence.
Other evidence suggests that microRNAs regulate the activity of at least a third of human proteinencoding
genes. This means there are very few cellular processes that do not happen under their
watch. Around 20 microRNAs, for instance, are made only in human embryonic stem cells. These
molecules could turn out to be the key to understanding how such cells remain in a state from
which they can become any other type of cell—the very reason embryonic stem cells hold such
great medical promise.
The existence of microRNAs may also help to explain why some creatures are more complex than
others. Until their discovery, this was something of a paradox. Knowing that DNA stores data that
then get translated into living organisms, and that the complexities of development must require
lots of information, biologists naturally expected that the more intricately formed an organism is,
the more genes it would have in its cells. They therefore struggled when they found that C.
elegans, a tiny worm that lacks a proper brain but is nevertheless widely studied by geneticists,
has about 20,000 genes—only a little bit short of the number in a human. Indeed, this seems to
be a general number for animals. Another geneticists' favourite, the fruit fly Drosophila, has a
similar number. But, of course, the genes in question are protein-coding genes. Add in the genes
whose RNA does other things and the balance changes.
It changes even more if exactly what those RNA molecules do is examined. Single microRNAs, for
example, often regulate the levels of hundreds of different proteins. They are like powerful strings
controlling copious protein puppets. Super-imposed on this, some types of regulatory RNA edit
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other kinds of RNA. The effect of extra genes for both of these sorts of RNA molecules is therefore
multiplicative rather than additive.
The picture that is emerging is thus one of “hard-wired” simple organisms, which mostly stick to
using RNA for fetching and carrying, and “soft-wired” complex ones that employ it in a
management capacity. In the complexity stakes, it is not how many protein-coding genes you
have, but how you regulate them, that counts.
What's up, Doc?
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Another consequence of RNA's rise to prominence is that researchers have a new source of
explanations for illness. Small RNAs have been linked to many types of cancer, to genetic diseases
of the central nervous system, and even to infections. Some scientists, for instance, think that
RNA molecules help the protein that causes Creutzfeldt-Jakob disease to recruit non-infectious
proteins to join its ranks.
The new RNA world is also a source of ideas about how diseases might one day be treated. In this
line of work it is best to start simple, which is why the main hunt for new drugs centres on a
technology called RNA interference, or RNAi (see article). This, in theory at least, promises to turn
down the production of any single protein to very low levels. That distinguishes it from microRNAs,
which control many proteins simultaneously.
A hypothetical RNAi drug might, for instance, become the ultimate analgesic by affecting the
activity of SCN9A, a gene recently pinpointed as the reason why a Pakistani street performer—who
put knives through his arms and walked on burning coals—could not feel pain. The technology has
also helped over-eating mice stay slim and live a fifth longer. That was done by choking an
insulin-receptor gene in the animals' fat cells. This made the cells less inclined to store every
calorie. The technique has even created edible cottonseed (for anyone who might want to try it)
by eliminating cotton's gossypol toxin. Not least, it can claim to have produced allergy-friendly
soya beans, by turning off the gene that encodes the protein that provokes the reaction.
It is also a technology that can be used at one remove. Recently, Michael White of the University
of Texas and his colleagues used RNAi not to treat lung cancer directly, but to convert tumorous
cells that do not respond to Taxol, a widely used anti-cancer drug, into cells that are sensitive to
it. They did this by silencing Taxol-suppressing genes that were usually active in those cancer
cells.
RNAi drugs work by mugging another sort of RNA—one of the classes of the molecule discovered
decades ago. These are the messenger-RNA molecules that shuttle information from DNA to the
cell's protein factories. The drugs themselves are short pieces of RNA made of strands about 21
genetic letters long. What is unusual about these molecules is that they have two parallel strands,
instead of a single one.
One of DNA's differences from RNA is that it comes as a double-stranded helix. Molecules of RNA
usually have only a single strand. When a double-stranded RNAi drug enters a cell, an “argonaute”
protein picks the molecule up and unzips it down the middle. It chops one strand in two and
discards those remnants. The other strand acts as a guide for the argonaute. It can pair with a
messenger-RNA molecule—at least, it can do so as long as this messenger contains a sequence of
21 letters that complement those of the drug.
When such RNA molecules do pair, the argonaute slices the messenger to oblivion like a swordswinging
samurai, just as it did with the other half of the original RNAi drug. Thus the gene whose
message it was carrying is silenced. This is how RNAi drugs stop the production of disease-related
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proteins at source—they hold the tap turned off whereas most medicines try to mop up a
continuous leak. Messenger destruction is specific because 21 letters of code are nearly always
enough to identify the instructions for one type of protein over another.
The most probable explanation for RNAi is that it evolved as a defence against viruses. Doublestranded
RNA is rare in nature, but viruses often make it when they reproduce. This means that
organisms which have evolved the ability to recognise and destroy double-stranded RNA molecules
have a competitive advantage over those that do not.
That is one example of the role of RNA in evolution. But there are many more. The evolution of
microRNAs, for instance, underlines their importance in the origin of complexity. Their number
appears to have ballooned when land plants and vertebrates evolved. But it is early days in this
research. Dave Bartel, of the Massachusetts Institute of Technology, is surveying grand lists of
small RNAs in mosses, flowers, worms, flies and mice in the hope that he will learn when different
families of microRNAs emerged and which genes these microRNAs are regulating.
Dr Bartel has already discovered microRNA genes interspersed among sets of protein-encoding
genes called Hox clusters. Hox clusters contain basic instructions about body plans, and the genes
within them are arranged in the order in which they influence their owner's shape during
development. In short, a Hox gene at one end of a cluster contains the information: “Give this
embryo a head”. The gene at the other end says: “And a tail, too”. The role of the interspersed
microRNAs is to regulate these high-level commands.
Ronald Plasterk, of the University of Utrecht, in the Netherlands, suggests that microRNAs are
important in the evolution of the human brain. In December's Nature Genetics, he compared the
microRNAs encoded by chimpanzee and human genomes. About 8% of the microRNAs that are
expressed in the human brain were unique to it, much more than chance and the evolutionary
distance between chimps and people would predict.
Such observations suggest evolution is as much about changes in the genes for small RNAs as in
the genes for proteins—and in complex creatures possibly more so. Indeed, some researchers go
further. They suggest that RNA could itself provide an alternative evolutionary substrate. That is
because RNA sometimes carries genetic information down the generations independently of DNA,
by hitching a lift in the sex cells. Link this with the fact that the expression of RNA is, in certain
circumstances, governed by environmental factors, and some very murky waters are stirred up.
It's evolutionary, my dear Watson
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What is being proposed is the inheritance of characteristics acquired during an individual's lifetime,
rather than as the result of chance mutations. This was first suggested by Jean Baptiste Lamarck,
before Charles Darwin's idea of natural selection swept the board. However, even Darwin did not
reject the idea that Lamarckian inheritance had some part to play, and it did not disappear as a
serious idea until 20th-century genetic experiments failed to find evidence for it.
The wiggle room for the re-admission of Lamarck's ideas comes from the discovery that small
RNAs are active in cells' nuclei as well as in their outer reaches. Greg Hannon, of the Cold Spring
Harbor Laboratory in New York State, thinks that some of these RNA molecules are helping to
direct subtle chemical modifications to DNA. Such modifications make it harder for a cell's codereading
machinery to get at the affected region of the genome. They thus change the effective
composition of the genome in a way similar to mutation of the DNA itself (it is such mutations that
are the raw material of natural selection). Indeed, they sometimes stimulate actual chemical
changes in the DNA—in other words, real mutations.
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Even this observation, interesting though it is, does not restore Lamarckism because such changes
are not necessarily advantageous. But what Dr Hannon believes is that the changes in question
sometimes happen in response to stimuli in the environment. The chances are that even this is
still a random process, and that offspring born with such environmentally induced changes are no
more likely to benefit than if those changes had been induced by a chemical or a dose of radiation.
And yet, it is just possible Dr Hannon is on to something. The idea that the RNA operating system
which is emerging into view can, as it were, re-write the DNA hard-drive in a predesigned way, is
not completely ridiculous.
This could not result in genuine novelty. That must still come from natural selection. But it might
optimise the next generation using the experience of the present one, even though the optimising
software is the result of Darwinism. And if that turned out to be commonplace, it would be the
paradigm shift to end them all.
Copyright © 2007 The Economist Newspaper and The Economist Group. All rights reserved.
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6/14/2007

Reading Between the Genes
Landmark Genome Study Shows Complexity of
Human 'Code'
Human Genome More Complicated Than Ever Realized, Scientists Say
By JOSEPH BROWNSTEIN
ABC News Medical Unit
June 14, 2007 —
In what is being hailed as a landmark in understanding the human genome, scientists from
over 35 research centers around the world released a collaborative study Wednesday
afternoon showing that our genetic makeup is much more complicated than previously thought.
The collaboration of researchers, known as the Encyclopedia of DNA Elements or ENCODE
consortium, looked at roughly 1 percent of the entire human genome, concluding that the 95
percent of the genome previously believed to be superfluous actually plays a major role in
regulating how DNA expresses itself.
The study brings a new dimension to determining both the impact of human genetics in clinical
medicine and how humans evolved differently from animals.
When researchers announced they had mapped the human genome in 2003, they knew it was
made up of over 3 billion base pairs of DNA.
However, only between 1.5 and 5 percent of that encompassing the areas known as "genes"
was involved in actually making proteins. The rest was termed "junk DNA."
But researchers felt that the remaining part of the genome had to have a purpose. In a paper
released in the journal Nature, scientists say they have found that much of that so-called junk
DNA is actually involved in regulating how genes build and maintain the body.
"Several years ago, we had completion of the Human Genome Project, but we didn't know
what to do with 95 percent of the DNA we'd found," said John Greally of the Albert Einstein
College of Medicine, who reviewed the study in the same issue of Nature. "This is going to be
a landmark."
Greally likens the genes to musical instruments, and the regulatory regions of the genome
found in this study to an orchestral score the instructions necessary to make the whole
symphony come together.
Genes With Accessories
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Reading Between the Genes
While Greally said the study is an important milestone in understanding the human genome,
the fact that the other parts of the DNA play a regulatory role is not surprising; rather, it is
something many scientists had expected.
He also said that this study begins to answer a question scientists have been asking for a
while: How do cells in the body operate differently when they all have the exact same DNA?
"What we've known for a long time ... is that every cell in the body has the same DNA, but
every cell uses different genes, and that's what defined them," said Greally.
While the current study mapped 1 percent of the genome and took four years, scientists feel
that the remaining 99 percent of the genome's regulatory regions will be mapped within the
next four to five years.
"It's just a matter of money," said Zhiping Weng, a biomedical engineering professor at Boston
University, who was one of the study leaders.
She said the accelerating pace of technology for sequencing DNA, and the number of labs that
will be interested in adding to the research, would speed up the remainder of the process.
"This is an enormous step forward," said Charles DeLisi, director of bioinformatics at Boston
University, who played a major role in the Human Genome Project, but was not involved in the
research for this particular study.
DeLisi sees this paper as the start of a new direction in the study of the human genome, where
we gain a broader understanding of how DNA really dictates human physiology.
"You'll learn a lot well before this project is completed," he said, referring to what he termed a
continuum of medical advances that would take place as researchers learned more about how
genetic defects contribute to various diseases like diabetes, heart disease and certain forms of
cancer.
Clinicians would then have a more accurate way of diagnosing patients for their risk of
developing specific diseases, DeLisi said.
Working in Harmony
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One of the most important parts of this study, DeLisi said, is the fact that many research labs
came together to work on it.
"We're all working together to make this happen a lot more rapidly than it would otherwise
happen," he said. "To me, that is exhilarating."
Francis Collins, head of the National Human Genome Research Institute, and Michael Snyder
of Yale University, echoed that sentiment at a press conference on the study Wednesday
morning. They indicated that having so many researchers working together so smoothly was
key to completing this important work.
This level of collaboration will continue as scientists aim to complete the mapping of the human
genome.
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Reading Between the Genes
"One of the important results is that we can do this," said Ewan Birney, head of genome
annotation at the European Molecular Biology Laboratory's European Bioinformatics Institute.
"We can gain this information genomewide."
Evolving Understanding
Birney said that the genome research will take a number of different directions, leading to a
variety of discoveries.
"Depending on your level of biological geekiness, you get excited about these stories at a
different level," said Birney.
For him, an important finding was how different human and animal DNA are.
As many as half of the functional parts of the genome varied between different mammals, said
Birney, who has looked at genomes for mice, rats, hedgehogs, platypuses and baboons,
among others.
Despite that diversity between humans and animals, Birney stresses that humans are still very
alike from one person to the next.
"Not only are we incredibly similar, the only sensible way to view our genetics is as one
population," he said. "We are far, far more similar to each other than we are different."
While the new advance adds to the understanding of the genome, researchers point out that
completing the mapping will take time. The complexity of the genome, Collins said, is
something he feels all the researchers are in awe of.
"We are intended to be complicated," he said, "and we obviously are."
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Bloomberg Printer-Friendly Page
`Junk DNA' Isn't Junk; Purpose Seen in Genetic Silent Majority
By John Lauerman
June 13 (Bloomberg) -- The vast majority of human DNA, sometimes called ``junk'' because it isn't
directly involved in making cellular proteins, is important after all, scientists said.
By looking at just 1 percent of the human genome, researchers found that at least half of the junk
regions are biologically relevant. Those areas are storehouses of information that contain switches to
regulate the actions of genes, according to a study released today by the journal Nature.
The finding reflects a $42-million research effort, involving 80 organizations in 11 countries, and is the
first step in analyzing the 98 percent of the DNA that isn't responsible for encoding proteins, the building
blocks of life. The approach brings genetic research to a new level, said Francis Collins, the director of
the National Human Genome Research Institute in Bethesda, Maryland.
``I don't think it should be surprising that what we have discovered is complex,'' he said. Referring to
humans, he said: ``We are intended to be complicated and we obviously are.''
Now researchers are trying to make sense out of the billions of components in DNA, the chain molecule
that forms genes. The study group, called the Encyclopedia of DNA Elements consortium, or ENCODE,
analyzed 44 sequences comprising 300 million components.
The findings help explain studies that have associated diseases such as prostate and breast cancer with
areas that are devoid of genes, said Michael Snyder, a professor of molecular biophysics and
biochemistry at Yale University in New Haven, Connecticut.
Zooming In
``These areas were thought to be junk DNA, and now it is clear that some of them encode regulatory
information,'' Snyder, who helped lead the study, said today in a telephone conference with reporters.
``This will help us our ability to zoom in on the regions that allow us to understand human disease.''
While only a tiny portion of the genome can make protein, the study found that most of its sequences
make RNA, the molecule that helps translate genetic information from DNA into proteins.
Once considered DNA's poor cousin, RNA has become an increasingly intriguing molecule. Researchers
have found that RNA can also block protein from being made, a process called RNA interference.
The study expanded on the versatility of RNA, the researchers said. For example, each gene in the area
studied by the international group made an average of five different kinds of RNA, Snyder said. Some of
the RNA's are previously unknown promoters that increase the activity of other genetic sequences, he
said.
`Much Better Map'
``We have a much better map of all the RNA's and the information that is expressed from the genome,''
he said. ``When you start prodding under the hood, it is very complicated and it is a lot of fun to try to
figure this out.''
While about half of the sequences the researchers looked at were already well known, the other half
were ``gene deserts'' that have no known function.
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The ENCODE scientists suspected that these areas held important information and purposes, said Ewan
Birney, a senior scientist at the European Molecular Biology Laboratory's European Bioinformatics
Institute in Hinxton, U.K., who also helped direct the study.
``People involved in genomics knew this stuff was not hanging around for the hell of it,'' he said. ``The
junk is not junk. It is very active, it does a lot of things.''
Scientists from Australia, Austria, Canada, Germany, Japan, Singapore, Spain, Sweden and Switzerland
also worked on the study.
To contact the reporter on this story: John Lauerman in Boston at jlauerman@bloomberg.net .
Last Updated: June 13, 2007 13:18 EDT
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6/14/2007

DNA study challenges basic ideas in genetics - The Boston Globe
DNA study challenges basic ideas in genetics
Genome 'junk' appears essential
By Colin Nickerson, Globe Staff | June 14, 2007
THIS STORY HAS BEEN FORMATTED FOR EASY PRINTING
A massive international study of the human genome has caused scientists to rethink some of the most basic
concepts of cellular function. Genes, it turns out, may be relatively minor players in genetic processes that are
far more subtle and complicated than previously imagined.
Among the critical findings: A huge amount of DNA long regarded as useless -- and dismissively labeled "junk
DNA" -- now appears to be essential to the regulatory processes that control cells. Also, the regions of DNA
lying between genes may be powerful triggers for diseases -- and may hold the key for potential cures.
The research, published in a set of papers in today's editions of the journals Nature and Genome Research,
raised far more questions than it answered -- and in a sense was a rallying cry for more and deeper research
into the functioning of the genome, often referred to as the "blueprint" for life.
"The instruction manual for life is written in a language we are only just beginning to understand," Francis
Collins, director of the federal government's National Human Genome Research Institute , said at a news
conference yesterday.
Page 1 of 2
Collins' s institute was among the more than 80 research institutions in North America, Europe, Asia, and
Australia that participated in the $42 million, four-year study, whose aim was to analyze 30 million units of
human DNA -- just 1 percent of the entire human genome -- to create an inventory of biologically functional
elements. The project is known as the Encyclopedia of DNA Elements, or ENCODE, and involved an
exhaustive scrutiny of 44 broad "sites" in the human genome, probing not just genes, but all material in the
samples.
"We're finding that a lot of the genome is as mysterious as 'dark matter' in physics; we know it is out there
doing something. The challenge is to find out what and why," said Thomas D. Tullius , professor of chemistry
at Boston University and one of the ENCODE researchers. "There were huge surprises; this research has
upset a lot of thinking about how the genome works."
He added in an interview: "There now appear to be thousands of places in the genome that were long thought
to be useless or meaningless, but which we now see to have a functional role. But we don't really understand
what that role is."
Most startling, according to researchers, is that some areas of the genome looming as crucial are regions that
don't contain specific instructions for making proteins. That recognition amounts to a sea change in basic
biology.
There are about 20,000 genes in the human body. But they are surrounded by other DNA material whose
exact purpose is unclear. Roughly 1 percent of the human genome is thought to be "protein-coding" -- that is,
genes. Another 4 percent had been thought to be "non coding DNA" that serves as on-off switches for the
genes, and the rest was seen as a sort of swamp with no clear purpose.
But the new work suggests that the "control regions" in the DNA are far more extensive, perhaps embracing
more than half of all DNA. Functions thought to be carried out by genes alone now appear to be managed by
multiple, overlapping segments of DNA. In addition, other portions of the genome are believed to be on
standby, as a toolbag to be utilized as humans evolve.
"It's like clutter in the attic," said Collins. "Most of the time, the human genome is operating on the 'first and
second floor,' with 5 percent of the genome doing what needs to be done on a daily basis. But over
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DNA study challenges basic ideas in genetics - The Boston Globe
evolutionary time, a much larger part of the genome, the stuff in the attic, becomes important. It's waiting for
natural selection to call for it."
The ENCODE research builds on the historic Human Genome Project, largely completed in 2003, which
cataloged the genes. Instead of the "big picture" look at the entire structure, the ENCODE project fine-combed
selected sites in the genome in extraordinary detail. Half the sites were known by scientists to affect gene
replication and protein coding; the other half were random samples from across the genome, including
swatches of "junk."
A long standing assumption in genetics has been that cellular organisms are run by genes, which instruct cells
to produce proteins thought to be the main driving mechanism in cells. But according to the study, obscure
sections of the genome, the "junk DNA," may play an even more critical role in health and evolution than
genes themselves.
"We're reshaping our understanding of which regions of the genome produce the critical information" that
allows organisms to function and evolve, said Michael Snyder, professor of molecular biophysics at Yale
University and one of the researchers.
Recent research into heart attacks and diabetes has made the startling discovery that the roots of disease
may lie in noncoding portions of DNA, not in the genes themselves.
In a significant finding, researchers discovered that "gene transcription" -- essential to the process by which
DNA builds proteins indispensable to life -- is occurring in regions between genes. They found that ribonucleic
acid, or RNA, long seen as another type of genetic code that directs cellular machinery to make proteins, is
also produced in stretches of the genome not involved in protein production. That suggests that these regions
have an important purpose, though still not understood, the scientists said.
"Transcription appears to be far more interconnected across the genome than anyone had thought," said
Collins, adding that the ENCODE findings are "moving us into a deeper understanding of how life works and
how, sometimes, things go wrong and disease occurs."
But untangling the tantalizing implications of the new findings will be the work of years.
"It's like reading a code, text jumbled together, and you're trying to make sense of it," said Zhiping Weng,
professor of biomedical engineering at Boston University and a researcher in the study. "This project provides
many new insights into the complex functional landscape of the human genome."
© Copyright 2007 The New York Times Company
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6/14/2007

Science: miracles and mysteries - The Boston Globe
GLOBE EDITORIAL
Science: miracles and mysteries
June 18, 2007
© Copyright 2007 The New York Times Company
THIS STORY HAS BEEN FORMATTED FOR EASY PRINTING
SCIENTISTS keep pulling the rug out from under their own feet. They acquire new knowledge that makes the
old, suddenly upended ideas seem quaintly uninformed.
After discoveries are made, there are surprised choruses of apparently we were wrong. One can only say
apparently, because the whole point of science is that there's always more to learn.
Last week two discoveries ushered in new insights. There's the news that in China, scientists had found the
fossil remains of Gigantoraptor erlianensis, a 3,100-pound, roughly 26-foot-long birdlike dinosaur that may
have had feathers. The fossil was found in 2005, but scientists spent two years studying it before announcing
its importance. The upset for science: Theories held that the more birdlike dinosaurs became, the smaller they
got. That's not so in this case. Large as he was, this dinosaur didn't live long enough to reach its full size.
Then there's the news that researchers have made a huge leap in understanding the human genome. The old
thinking was that genes, which are made of DNA, determine how a living body is cobbled together. The new
thinking is that genes work with other kinds of DNA, so-called junk DNA, that had been seen as less important.
Now scientists say junk DNA also plays an important role in regulating cells.
The finding is the result of a four-year, $42 million international effort that involved 80 institutions and looked at
just 1 percent of the entire human genome, some 30 million units of DNA. What exactly does junk DNA do,
and how does it function? These questions have yet to be answered. The goal is to create an encyclopedia of
the various DNA elements of the human genome, a kind of instruction manual on how DNA works.
Such findings are an implicit invitation to children to become scientists and continue the work of their academic
ancestors. But to take their rightful place in the world's laboratories, children need to be in schools with
teachers who can engage them in the sciences, immersing them in current thought and enticing them to
pursue what's not known. Children need a clear sense of the scientific mission and enough moxie to keep
challenging conventional wisdom.
Scientific progress is also an implicit appeal to government to keep research funding flowing -- both to solve
known problems such as chronic diseases, and to gather knowledge for knowledge's sake. Last week, the
American Association for the Advancement of Science highlighted efforts in the US House to spend $21 billion
more on federal research funding than President Bush has proposed.
It would be money well spent: on science and on the profound endeavor of pursuing the unknown.
http://www.boston.com/news/globe/editorial_opinion/editorials/articles/2007/06/18...
Page 1 of 1
6/18/2007

CBSNews.com: Print This Story
DNA Decoding Landmark
June 13, 2007
Page 1 of 2
(WebMD) Researchers announced they have decoded the first 1% of the human genetic code — and the results already are
rewriting the rules of biology.
The massive, four-year, $42 million effort, organized by the U.S. National Human Genome Research Institute, is called the
Encyclopedia of DNA Elements, or ENCODE. It involved 35 researcher groups from 80 organizations scattered across 11
nations.
It's a huge success, says NHGRI Director Francis Collins, M.D., Ph.D. The project builds on the Human Genome Project,
which in 2003 finally pieced together the DNA sequences that make up the human genome.
"But the genome is written in a language we are still trying to learn how to understand," Collins said in a news
conference. "ENCODE is building an encyclopedia to tell us what functions are encoded in this remarkable 3-billion-letter
script. That script ... somehow carries within it all of the instructions necessary to take a single-celled embryo and turn it into
the very complex biological entity called a human being."
Collins says that the success of this pilot project means that over the next four years, researchers will undertake a $100
million effort to decode the remaining 99% of the human genome.
The early findings already rewrite the human biology rulebook — especially the rules about what genes are and what they do.
The biggest surprises:
Human genes aren't discrete boxes of DNA. Instead, DNA from all over the genome contributes to the units of inheritance
we call genes.
It was once thought that all functional genes encode protein molecules, the building blocks of the body. The rest of the
DNA was called "junk DNA." Now it turns out that this "junk" is just as important as the rest of the genome.
Genes, once supposed to have only one specific function, are now shown to have, on average, at least five different
functions.
Very few genes actually code for proteins. The vast majority of genes regulate the function of other genes, telling them
when, where, and how they should work.
Many of our genes are just along for the ride, doing us neither good nor harm. But these "bystander" genes may be the
stuff from which future
human evolution will be made.
It's all much more complicated than had been supposed, says Michael Snyder, Ph.D., director of the Yale University Center
for Genetics and Proteomics.
"I envision this like a sports car," Snyder said at the news conference. "When you first look at it, it looks pretty, simple, and
elegant. But as soon as you start prodding under the hood, you find out how complicated it is."
For medicine, the new findings hold a great deal of promise. Nearly all of the recently discovered genes linked to disease risk
turn out to be the regulatory genes.
"This may be a good thing, because there is only a subtle tweaking of a gene in a person with disease," Collins
said. "Changing that with a small-molecule drug has a good chance of success. We will have some work to do to figure out
how that works, and whether the gene is expressed too high, too low, in the wrong place, and so on."
Finishing the human genome encyclopedia will give medical research an extraordinarily valuable tool, says Ewan Birney,
Ph.D., leader of the Birney Research Group at the European Bioinformatics Institute in Cambridge, England.
"We can now start to say why it is that a certain part of the genome is changing the risk for a certain disease," Birney said at
the news conference. "And as we go across the genome, we will be providing researchers with a broader and broader set of
annotations to understand how diseases really happen, and therefore get more insight into how to cure them."
The ENCODE Project Consortium reports the findings in the June 14 issue of the journal Nature. Twenty-eight companion
papers appear in the June issue of Genome Research.
http://www.cbsnews.com/stories/2007/06/13/health/webmd/printable2926209.shtml
6/14/2007

CBSNews.com: Print This Story
By Daniel DeNoon
Reviewed by Louise Chang
B)2005-2006 WebMD, Inc. All rights reserved.
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Online NewsHour: Update | 'Landmark' Study Changes Long-held DNA Beliefs |...
Online NewsHour
REGION: North America
TOPIC: Science & Technology
'Landmark' Study Changes Long-held DNA Beliefs
Posted: June 14, 2007, 4:50 PM ET
A four-year international study of the human genome has prompted scientists to rethink some of their most basic ideas about
how DNA functions.
The researchers found that individual genes interact with one
another in more complex ways than previously suspected. They
also found that large stretches of DNA once called "junk DNA"
because they had no known purpose may actually play a
significant role in regulating biological processes.
The findings point to the need for much more research, the
researchers say, and could influence the way scientists search
for the genetic causes of diseases.
Page 1 of 2
"This is a landmark in our understanding of human biology,"
Francis Collins, director of the National Human Genome Research Institute, said at a news conference Wednesday.
The institute was one of more than 80 research institutions from 11 countries that participated in the Encyclopedia of
DNA Elements (ENCODE) project. The researchers published their findings Thursday in a series of articles in the
journals Nature and Genome Research.
The human genome consists of a string of more than 3 billion DNA letters. However, only about 3 percent of those DNA
letters are part of the approximately 20,000 genes that contain instructions for making proteins, which regulate the body's
cellular processes. The protein-making is a two-step process. First, the DNA in the gene is transcribed into RNA, and
then that RNA serves as a template to produce a protein.
Until now, most genome research has focused on investigating genes -- often the genes thought to cause or contribute to
heritable diseases -- and has ignored the vast stretches of so-called "junk DNA."
The new study, in contrast, picked 44 sites on the genome to comb through in detail. Some were chosen because they
already contained genes of interest, but others were randomly chosen to include large stretches of DNA with no known
purpose.
The researchers found, to their surprise, that much of the supposedly purposeless DNA was transcribed into RNA --
leading them to believe that the DNA serves some purpose, although they don't yet know what that purpose might be.
"There now appear to be thousands of places in the genome that were long thought to be useless or meaningless, but
which we now see to have a functional role," ENCODE researcher Thomas Tullius of Boston University told the Boston
Globe. "But we don't really understand what that role is."
One role, the researchers say, may be to act as control regions that help regulate individual genes and turn them on and
off. Researchers already knew that some sections of DNA performed this function, but the new research suggests that it
might be more widespread than previously thought.
Other segments of DNA may simply be "clutter in the attic," according to Collins. However, even this clutter could serve a
purpose, providing basic building blocks for evolution to call into use when needed.
http://www.pbs.org/newshour/updates/science/jan-june07/dna_06-14.html
6/15/2007

Online NewsHour: Update | 'Landmark' Study Changes Long-held DNA Beliefs |...
"Most of the time, the human genome is operating on the 'first and second floor,' with 5 percent of the genome doing
what needs to be done on a daily basis," Collins said at the news conference. "But over evolutionary time, a much larger
part of the genome, the stuff in the attic, becomes important. It's waiting for natural selection to call for it."
---- Compiled from wire reports and other media sources
Support the kind of journalism done by the NewsHour...Become a member of your local PBS station.
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Page 2 of 2
6/15/2007

Print This Article | Close this window
Human instruction book not so simple: studies
Wed Jun 13, 2007 8:52PM BST
By Maggie Fox, Health and Science Editor
WASHINGTON (Reuters) - An in-depth examination of the human DNA map has turned basic biology concepts
upside-down and may even rewrite the book on evolution and some causes of disease, researchers said on
Wednesday.
They found there was far more to genetics than the genes themselves and determined there was no such thing as
"junk DNA" but that some of the most useless-looking stretches of DNA may carry important information.
Thirty-five teams of researchers from 80 different organizations in 11 countries teamed up to share notes on just 1
percent of the human genome.
Their findings, the start of the Encyclopedia of DNA Elements or ENCODE Project, were published in the journals
Nature and Genome Research.
"This is a landmark in our understanding of human biology," said Dr. Francis Collins, head of the National Human
Genome Research Institute, which funded much of the work.
When the human genome was published in 2003, some scientists voiced surprise that human beings had only
about 30,000 genes. Rice, for instance, has 50,000.
The new study confirms what many genetics experts had suspected -- the genes are important, but so is the other
DNA, the biological code for every living thing.
What they discovered is that even DNA outside the genes transcribes information. Transcription is the process that
turns DNA into something useful -- such as a protein.
ACTION OUTSIDE THE GENES
Much of this action is going on outside the genes in the so-called regulatory regions that affect how and when a
gene activates, Collins said.
The researchers discovered 4,491 of these so-called transcription start sites, "almost tenfold more than the
number of established genes," they wrote in the Nature paper.
Ewan Birney of the European Molecular Biology Laboratory's European Bioinformatics Institute in Cambridge said
this helped explain how such a complex creature as a human arose from just four letters of code repeated over
and over.
"The junk is not junk. It is really active," Birney told reporters. This could be useful in understanding and treating
disease.
"One could imagine that that actually could be a good thing because it would tell you that there is a subtle
http://uk.reuters.com/articlePrint?articleId=UKN1338205520070613
Page 1 of 2
6/13/2007

tweaking of the expression of that particular gene, and therefore that particular protein in a person at high risk --
they are making a little too much or not quite enough," Collins added.
Drugs might easily be designed to compensate, he said.
The researchers did find some DNA that appears to do nothing, and it can mutate without causing any damage.
Collins likened these stretches of DNA to boxes in the attic.
"It is not the sort of clutter that you get rid of without consequences because you might need it. Evolution may
need it," he said.
That little extra padding might be just what an animal needs to adapt to some unforeseen circumstance, the
researchers said. "They may become useful in the future," Birney said.
© Reuters 2006. All rights reserved. Republication or redistribution of Reuters content, including by caching, framing or similar means, is expressly
prohibited without the prior written consent of Reuters. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the
Reuters group of companies around the world.
Reuters journalists are subject to the Reuters Editorial Handbook which requires fair presentation and disclosure of relevant interests.
http://uk.reuters.com/articlePrint?articleId=UKN1338205520070613
Page 2 of 2
6/13/2007

Human Genome Yields Up More Secrets - washingtonpost.com
Human Genome Yields Up
More Secrets
By E.J. Mundell
HealthDay Reporter
Wednesday, June 13, 2007; 12:00 AM
WEDNESDAY, June 13 (HealthDay News) -- In
what's being hailed as a milestone in human
genetics research, an international consortium of
scientists announced Wednesday new data that
could revolutionize how scientists study health
and disease.
Page 1 of 3
An exhaustive look at only 1 percent of the
human genome produced two major findings: a
vast amount of seemingly useless genes formerly called "junk DNA" may, in fact, be crucial to
regulatory processes governing cells; and "epigenetic" factors outside of genes are probably
big players behind many diseases.
The results of the Encyclopedia of DNA Elements (ENCODE) Project, published in the June 14
issue ofNature, are "moving us into a deeper understanding of how life works and how,
sometimes, things go wrong and disease occurs," Dr. Francis Collins, director of the U.S.
National Human Genome Research Institute, told reporters at a morning news conference.
The completion of the Human Genome Project in April 2003 was an historic achievement,
resulting in a catalog of more than 30,000 genes that make up the species' genetic blueprint.
Those genes are comprised of 3 billion individual nucleotides -- labeled A, C, G, or T -- which
combine to form genetic code. All of this is packed and bound into chromosomes as material
collectively called chromatin.
"This script is written in this apparently simple alphabet with just four letters, but somehow
carries within it all of the instructions necessary to take a single-cell embryo and turn it into a
very complex biological entity called a human being," said Collins, whose institute is the major
source of funding for the $41 million project.
It is one thing to map the whole genome on the "macro" level, the experts noted. But what the
ENCODE team -- 35 groups from 80 organizations worldwide -- is seeking to do is examine, in
much more detail, just 1 percent of the genome.
About half of this 1 percent involves areas that were known by scientists to influence gene
replication and protein coding to make the building blocks of life. The other half was a random
sample meant to include other aspects of the genome, including so-called "junk DNA."
"When they first sequenced the genome, [scientists] were surprised at how little DNA was
involved in protein coding regions," explained Ewan Birney of the European Bioinformatics
Institute in Hinxton, England.
http://www.washingtonpost.com/wp-dyn/content/article/2007/06/13/AR200706130...
6/13/2007

Human Genome Yields Up More Secrets - washingtonpost.com
Page 2 of 3
Birney, who headed up the two-and-a-half year analysis of the ENCODE data, noted that just
1.5 percent of the "letters" in the genome actually make cellular proteins. So, his team
wondered, what was the other 98.5 percent doing?
"People rather dismissively called the rest of it 'junk DNA,' " he said. But the ENCODE data
suggest that this genetic material is, in fact, very active.
"One of the big surprises is that the regions between genes seem to be alive, not only with
regulatory regions -- which we suspected -- but also there's a lot of [gene] transcription," Birney
said. Transcription is the process whereby DNA transcribes its information into usable proteins.
The researchers also discovered another, less obvious purpose to a lot of genetic material.
They noticed that up to 70 percent of "functional regions" in the genomes of both humans and
other mammals were what Birney called "neutral." These neutral genetic blips popped up
frequently and didn't help or hinder the organism, in terms of activities needed to sustain life.
But Collins and other experts believe the neutral regions may, in fact, be key players in
evolution and disease, swinging into action occasionally and triggering either helpful or harmful
changes.
"It's like clutter in the attic," Collins said. "It's not the kind of clutter that you would get rid of
without consequences, however, because you might need it."
"Most of the time the human genome is operating on the 'first and second floor,' with maybe 5
percent of the genome doing whatever needs to be done in terms of daily activities," Collins
added. "But over evolutionary time, a much larger fraction of the genome -- this stuff up in the
attic -- becomes important. In fact, it's probably responsible for getting us where we are in
terms of [our] complexity. It's still there, waiting for natural selection to call upon it."
ENCODE is also revealing that epigenetics -- factors that modify the function of DNA but don't
change its sequence -- are a major player in disease.
For example, a team at the University of Virginia has found that the degree to which DNA is
bound within the chromosome's chromatin structure strongly influences whether that gene can
express, or produce, a protein.
While smaller studies have hinted at that before, "this genome-wide survey really shows that
these factors are beautifully coordinated," lead researcher Dr. Anindya Dutta, a professor of
molecular genetics at the university, toldHealthDay. "Portions of the chromosome that are
lightly packed are replicated early, and they also have the highest amount of gene expression."
That means that a too-loose or too-tight "packing" can cause changes in how a gene functions,
much like a mutation would. The ENCODE survey found that, "in cancer cells, this happens in
20 percent of our genes," Dutta noted.
Indeed, revelations from ENCODE should, in the long run, greatly enhance research into a
variety of diseases, the experts said. The findings come on the heels of a major study,
released last week inNature, in which British scientists substantially increased the number of
genes implicated in such common diseases as bipolar disorder, diabetes, heart disease and
rheumatoid arthritis.
http://www.washingtonpost.com/wp-dyn/content/article/2007/06/13/AR200706130...
6/13/2007

Human Genome Yields Up More Secrets - washingtonpost.com
In many cases, the new complexity arising from ENCODE means that "it will take us a bit
longer to sort out exactly what is the mechanism of disease risk," Collins said. "We will have
some work to do to figure out exactly how [a genetic aberration] works and what is the
consequence."
The results announced Wednesday, he added, are merely those of a pilot project. "We aim to
scale this up in the not-too-distant future and apply these same approaches to the entire
human genome," he said.
And, Collins noted, "I think that we are all, regardless of our philosophical perspective, rather
awed by what we are seeing."
A host of related articles on the ENCODE project were also published Wednesday in the June
issue ofGenome Research.
Moe information
For more on the human genome, visit the U.S. National Human Genome Research Institute.
SOURCES: June 13, 2007, news conference,Nature, including Francis Collins, M.D., Ph.D.,
director, U.S. National Human Genome Research Institute, Bethesda, Md., and Ewan Birney,
Ph.D., head, genome annotation, European Molecular Biology Laboratory's European
Bioinformatics Institute, Hinxton, England; Anindya Dutta, M.D., professor, biochemistry and
molecular genetics, University of Virginia, Charlottesville
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http://www.washingtonpost.com/wp-dyn/content/article/2007/06/13/AR200706130...
Page 3 of 3
6/13/2007

Intricate Toiling Found In Nooks of DNA Once Believed to Stand Idle - washingt...
Intricate Toiling Found In Nooks of DNA
Once Believed to Stand Idle
By Rick Weiss
Washington Post Staff Writer
Thursday, June 14, 2007; A01
The first concerted effort to understand all the inner workings of the
DNA molecule is overturning a host of long-held assumptions about
the nature of genes and their role in human health and evolution,
scientists reported yesterday.
The new perspective reveals DNA to be not just a string of biological
code but a dauntingly complex operating system that processes
many more kinds of information than previously appreciated.
The findings, from a project involving hundreds of scientists in 11
countries and detailed in 29 papers being published today, confirm
growing suspicions that the stretches of "junk DNA" flanking
hardworking genes are not junk at all. But the study goes further,
indicating for the first time that the vast majority of the 3 billion
"letters" of the human genetic code are busily toiling at an array of
previously invisible tasks.
The new work also overturns the conventional notion that genes are
discrete packets of information arranged like beads on a thread of
DNA. Instead, many genes overlap one another and share stretches
of molecular code. As with phone lines that carry many voices at
once, that arrangement has prompted the evolution of complex
switching, splicing and silencing mechanisms -- mostly located
between genes -- to sort out the interwoven messages.
The new picture of the inner workings of DNA probably will require
some rethinking in the search for genetic patterns that dispose
people to diseases such as diabetes, cancer and heart disease, the
scientists said, but ultimately the findings are likely to speed the development of ways to
prevent and treat a variety of illnesses.
Page 1 of 4
One implication is that many, and perhaps most, genetic diseases come from errors in the
DNA between genes rather than within the genes, which have been the focus of molecular
medicine.
Complicating the picture, it turns out that genes and the DNA sequences that regulate their
activity are often far apart along the six-foot-long strands of DNA intricately packaged inside
each cell. How they communicate is still largely a mystery.
Altogether, the new project shows that the simple sequence of DNA letters revealed to great
http://www.washingtonpost.com/wp-dyn/content/article/2007/06/13/AR200706130...
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Intricate Toiling Found In Nooks of DNA Once Believed to Stand Idle - washingt...
Page 2 of 4
fanfare by the $3 billion Human Genome Project in 2003 was but a skeletal version of the
human construction manual. It is the alphabet, but not much more, for a syntactically
complicated language of life that scientists are just now beginning to learn.
"There's a lot more going on than we thought," said Francis Collins, director of the National
Human Genome Research Institute, the part of the National Institutes of Health that financed
most of the $42 million project.
"It's like trying to read and understand a very complicated Chinese novel," said Eric Green, the
institute's scientific director. "The take-home message is, 'Oh, my gosh, this is really
complicated.' "
The findings come from the Encyclopedia of DNA Elements project, nicknamed Encode. While
much of the decades-long effort to understand DNA's role in health and disease has been
driven by scientists' interest in particular genes, Encode focused on a representative 1 percent
of the genome. Using a variety of experimental and computational approaches, the
researchers sought to catalogue everything going on there.
The 3 1/2 -year effort was designed as a pilot project to see whether it would be practical to
study the entire genome in such depth and to hasten the development of cheaper tools to do
so. Encode was so successful, Collins said, that the remaining 99 percent of the genome is
expected to be studied the same way for $100 million.
The teams targeted 44 areas along the genome, half of them already of interest and half
chosen at random to include gene-dense "urban" areas and expanses of seemingly inactive
genetic "desert."
Perhaps most surprising was how much of the human genome is at work at any given time, the
scientists said.
Researchers have long known that only about 2 percent of human DNA is involved in making
proteins, the molecular workhorses inside cells. That involves a two-step process in which a
stretch of DNA -- a gene -- serves as a template to produce a strand of RNA, which is then
used as a template to produce a protein.
Recent studies had shown that some snippets of DNA between genes also are transcribed into
RNA even though they do not go on to make proteins. Surprisingly, though, the new work
shows that most of a cell's DNA gets transcribed, raising questions about what all that RNA is
doing.
Some of it may be doing nothing. "It may be like clutter in the attic," Collins said, noting that
clutter could be useful when conditions change and evolution needs new material to work with.
But much of it seems to be playing crucial roles: regulating genes, keeping chromosomes
properly packaged or helping to control the spectacularly complicated process of cell division,
which is key to life and also is at the root of cancer.
"We are increasingly being forced to pay attention to our non-gene DNA sequences," John M.
Greally of the Albert Einstein College of Medicine in New York wrote in a commentary in
today's issue of the journal Nature, where one of the new reports is being published. The 28
http://www.washingtonpost.com/wp-dyn/content/article/2007/06/13/AR200706130...
6/14/2007

Intricate Toiling Found In Nooks of DNA Once Believed to Stand Idle - washingt...
other papers appear in today's issue of Genome Research.
Greally noted that several recent studies have found that people are more likely to have Type
2 diabetes and other diseases if they have small mutations in non-gene parts of their DNA that
were thought to be medically irrelevant.
Another aspect of Encode had researchers looking at the equivalent 1 percent of the genomes
of more than 20 other mammals, and those results are forcing them to rethink the interplay
between genetics and evolution.
The expectation was that many of the most active DNA sequences in humans would be
prevalent in other mammals, too, because evolution tends to save and reuse what works best.
But more than half were not found in other creatures, which suggests they may not be that
important in people, either, said Ewan Birney of the European Bioinformatics Institute in
Cambridge, England, a coordinator of the Encode effort.
"I think of them as gate-crashers at a party," Birney said. "They appeared by chance over
evolutionary time . . . neither to the organism's benefit nor to its hindrance. That is quite an
interesting shift in perspective for many biologists."
Although the new view of the genome may at first complicate efforts to identify DNA stretches
of prime medical interest, Encode is sure to help in the long run, said Michael Snyder of Yale
University, another coordinator.
"Defining the functional elements helps us zoom in to look for differences in sequence that
might relate to disease," he said.
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Page 3 of 4
6/14/2007

Genetics Revolution Arrives
Article Link: http://www.webmd.com/news/20070613/genetics-revolution-arrives
Health News
Genetics Revolution Arrives
First Chapter of Human DNA ‘Encyclopedia’ Rewrites Biology
By Daniel J. DeNoon
WebMD Medical News
Reviewed by Louise Chang, MD
June 13, 2007 -- Researchers today announced they have decoded the first 1% of the human genetic code --
and the results already are rewriting the rules of biology.
The massive, four-year, $42 million effort, organized by the U.S. National Human Genome Research Institute,
is called the Encyclopedia of DNA Elements, or ENCODE. It involved 35 researcher groups from 80
organizations scattered across 11 nations.
It's a huge success, says NHGRI Director Francis Collins, MD, PhD. The project builds on the Human Genome
Project, which in 2003 finally pieced together the DNA sequences that make up the human genome.
"But the genome is written in a language we are still trying to learn how to understand," Collins said in a news
conference. "ENCODE is building an encyclopedia to tell us what functions are encoded in this remarkable 3billion-letter
script. That script ... somehow carries within it all of the instructions necessary to take a singlecelled
embryo and turn it into the very complex biological entity called a human being."
Collins says that the success of this pilot project means that over the next four years, researchers will
undertake a $100 million effort to decode the remaining 99% of the human genome.
The early findings already rewrite the human biology rulebook -- especially the rules about what genes are and
what they do. The biggest surprises:
Human genes aren't discrete boxes of DNA. Instead, DNA from all over the genome contributes to the units
of inheritance we call genes.
It was once thought that all functional genes encode protein molecules, the building blocks of the body. The
rest of the DNA was called "junk DNA." Now it turns out that this "junk" is just as important as the rest of the
genome.
Genes, once supposed to have only one specific function, are now shown to have, on average, at least five
different functions.
Very few genes actually code for proteins. The vast majority of genes regulate the function of other genes,
telling them when, where, and how they should work.
Many of our genes are just along for the ride, doing us neither good nor harm. But these "bystander" genes
may be the stuff from which future human evolution will be made.
It's all much more complicated than had been supposed, says Michael Snyder, PhD, director of the Yale
University Center for Genetics and Proteomics.
Page 1 of 2
"I envision this like a sports car," Snyder said at the news conference. "When you first look at it, it looks pretty,
simple, and elegant. But as soon as you start prodding under the hood, you find out how complicated it is."
For medicine, the new findings hold a great deal of promise. Nearly all of the recently discovered genes linked
http://www.webmd.com/news/20070613/genetics-revolution-arrives
6/14/2007

Genetics Revolution Arrives
to disease risk turn out to be the regulatory genes.
Page 2 of 2
"This may be a good thing, because there is only a subtle tweaking of a gene in a person with disease," Collins
said. "Changing that with a small-molecule drug has a good chance of success. We will have some work to do
to figure out how that works, and whether the gene is expressed too high, too low, in the wrong place, and so
on."
Finishing the human genome encyclopedia will give medical research an extraordinarily valuable tool, says
Ewan Birney, PhD, leader of the Birney Research Group at the European Bioinformatics Institute in Cambridge,
England.
"We can now start to say why it is that a certain part of the genome is changing the risk for a certain disease,"
Birney said at the news conference. "And as we go across the genome, we will be providing researchers with a
broader and broader set of annotations to understand how diseases really happen, and therefore get more
insight into how to cure them."
The ENCODE Project Consortium reports the findings in the June 14 issue of the journal Nature. Twenty-eight
companion papers appear in the June issue of Genome Research.
SOURCES: Birney, E. Nature, June 14, 2007; vol 447: pp 799-816. Greally, J.M. Nature, June 14, 2007; vol
447: pp 782-783. News conference, June 13, 2007, with Francis Collins, MD, PhD, director, National Human
Genome Research Institute, NIH, Bethesda, Md. Michael Snyder, PhD, director, Center for Genetics and
Proteomics, Yale University, New Haven, Conn. Ewan Birney, PhD, senior scientist, Birney Research Group,
European Bioinformatics Institute, Cambridge, England. News release, NIH. News release, European
Molecular Biology Laboratory. News release, European Bioinformatics Institute.
© 2007 WebMD, Inc. All rights reserved.
http://www.webmd.com/news/20070613/genetics-revolution-arrives
6/14/2007

Scientific American: The 1 Percent Genome Solution
June 13, 2007
The 1 Percent Genome Solution
Tiny slice of genome reveals bustling activity in the gaps between genes
The first results from a massive project to exhaustively catalogue all
the functions of the human genome reveal a hotbed of activity in the
gaps between genes. An international consortium of researchers
sifted through 1 percent of the genome looking for pieces of DNA that
are copied by the cell or help to control gene activity. The results
indicate that most DNA is copied into molecules of RNA, including the
long stretches between genes, and that genes overlap and interact
with each other much more than researchers previously believed.
"We all suspected there was interesting stuff going on in these regions
[between genes], and sure enough there is," says bioinformatician
Ewan Birney of the European Bioinformatics Institute near Cambridge,
England, a member of the project's computer analysis team.
Although researchers do not yet know the biological significance of
these discoveries, they say that fully cataloguing the genome may
help them understand how genetic variations affect the risk of
contracting diseases such as cancer as well as how humans grow
from a single-celled embryo into an adult. The next phase of the
project, set to begin later this year, will attempt to inventory the full
genome.
A genome consists of only four different nucleotide bases, or DNA
subunits, arranged in a particular sequence. The publication of the
human genome in 2001 revealed its sequence—the significance of
which remains a mystery. In particular, genes account for only 1.2
percent of the genome's three billion bases. Once dismissed as "junk
DNA," researchers have found that some of these so-called
noncoding regions are shared among mammals, suggesting they play
an important function.
To help uncover those functions and identify other important
sequences, 35 research groups joined forces in 2003 to create the
encyclopedia of DNA elements (ENCODE) project. This consortium
selected 44 separate sections of the genome that included regions of
high to low gene density and high to low similarity between mouse
and human.
Like treasure hunters combing a vast beach with metal detectors,
ENCODE researchers sifted through their patch of the genome in
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Scientific American: The 1 Percent Genome Solution
multiple ways that are described, along with the results, in a Nature
paper published online today and in a special issue of Genome
Research.
A major part of the project was identifying sequences that cells copy,
or transcribe, into RNA molecules. Cells make proteins from RNA they
copy from genes, but some RNAs play roles by themselves. In
addition, some studies have found evidence that species from flies
and worms to humans copy large amounts of RNA from noncoding
DNA, with no apparent purpose. Nevertheless, "before ENCODE, I
think a lot of people were skeptical of how real intergenic activity was,"
says bioinformatician and consortium member Mark Gerstein of Yale
University.
Although genes make up only 3 percent of the ENCODE sequence,
the consortium found that 93 percent of the sequence is transcribed.
Some of the transcripts hail from noncoding DNA, the researchers
report, but those that do match up with the 399 ENCODE genes
overlap with each other extensively.
Transcripts from 65 percent of the genes incorporate pieces of DNA
from relatively far outside of the genes or even from one or two other
genes, says molecular biologist and consortium member Tom
Gingeras of Affymetrix, a genome technology company in Santa
Clara, Calif. Researchers know that cells chop single genes into
shorter pieces called exons, which they mix and match into one
transcript for creating a protein. Gingeras says the ENCODE findings
confirm recent reports that humans and flies sometimes combine
exons from two different genes.
Based on the transcript sequences, the researchers identified 1,437
new promoters—short DNA sequences where transcription begins—in
or between genes, on top of the 1,730 promoters they knew of. That is
nearly ten promoters per gene, Birney says. He adds that the
abundance of transcripts that overlap each gene suggests that the
very term "gene" should mean something different inside the cell
nucleus, where transcription takes place, than outside of it, where
finished proteins go.
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Scientific American: The 1 Percent Genome Solution
Project members also catalogued sequences that mark areas where
DNA unwinds from the round histone proteins that maintain the shape
of chromosomes, allowing the cell's transcription machinery to
activate genes in those areas. They discovered some potentially
unwound areas that are far from promoters and may therefore play
some other role, Birney says.
The consortium found that 5 percent of the studied sequence has
been conserved among 23 mammals, suggesting that it plays an
important enough role for evolution to preserve while species have
evolved. But of all the new ENCODE sequences identified as
potentially important, only half fall into the conserved group.
These unconserved sequences may be "bystanders," Birney says—
consequences of the genome's other functions—that neither help nor
hurt cells and may have provided fodder for past evolution.
They could also simply maintain a useful DNA structure or spacing
between pieces of DNA regardless of their particular sequence, says
genomics researcher T. Ryan Gregory of the University of Guelph in
Ontario, who was not part of the consortium.
"The biological insights are mainly incremental at this point," says
genome biologist George Weinstock of the Baylor College of Medicine
in Houston, which he says is to be expected of such a pilot study.
"This is a 'community resource' project, like a genome project, that
makes lots of new data available to the community, who then dig into
it and mine it for discoveries."
Gregory says the results, although still cryptic, do hint at new
functions and a more complicated genome. "This study shows us how
far we are from a comprehensive understanding of the human
genome."
© 1996-2007 Scientific American, Inc. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
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The Scientist : First pages of regulation "Encyclopedia"
June 2007
Table of Contents
Editorial
Columns
Features
Editorial Advisory Board
NEWS
By Melissa Lee Phillips
Comment on this news story
First pages of
regulation
"Encyclopedia"
Many regulatory sequences in the human genome are
not conserved
[Published 13th June 2007 05:02 PM GMT]
http://www.the-scientist.com/news/home/53280/
Approximately half of the functional regulatory
sequences in the human genome appear to lack
conserved sequences, according to an analysis of
functional elements in 1% of the genome. The
finding comes from the four-year pilot ENCODE
Encyclopedia of DNA Elements project, whose
results are published in this week's Nature.
This lack of evolutionary constraint is "clearly one
of the most interesting findings in the paper," said
Eric Schadt of Rosetta Inpharmatics in Seattle,
Wash., who was not involved in the work. It's
possible that variations in regulatory sequences
between people could help explain individual
differences in disease susceptibility, giving these
findings "huge implications," Schadt told Nature.
The ENCODE project also analyzed many other
aspects of functional non-coding regions of the
human genome. "Finally, we're going to be able to
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have some type of a map that will allow us to
interpret the significance of any kind of human
genetic variation, not just what is occurring in
genes," said ENCODE co-chair John
Stamatoyannopoulos of the University of
Washington in Seattle. A series of papers on
ENCODE data is also appearing this week in
Genome Research.
The pilot phase of the project combined more
than 200 new experimental and computational
data sets from a consortium of 35 research groups
to identify functional elements encoded in about
30 megabases of the human genome. Researchers
analyzed DNA from diverse regions throughout the
genome, Stamatoyannopoulos said, so that
researchers can confidently extrapolate results to
the entire genome. "This is the first time that so
many different data types have been analyzed
over the exact same regions in the exact same cell
types," he told Nature.
The consortium's analyses revealed that most of
the human genome is transcribed, even though
just a small fraction of these transcripts are
translated into protein. "The ENCODE work is
really confirming that there is a significant amount
of intergenic and intronic transcription," said
Douglas Mortlock of Vanderbilt University in
Nashville, Tenn., who was not involved in the
work. "A lot of this has been suggested to exist,
but it's sort of nice to see confirmation on a larger
scale." However, the biological role of many of
these transcripts is not yet clear, he added. "A lot
of that transcription may not be functional."
The data also showed that the same regions of
DNA are often transcribed multiple times in an
overlapping fashion, confirming a previous
hypothesis. "What we think of as genes are
actually overlapping each other to a much greater
extent than was previously thought,"
Stamatoyannopoulos said. "The whole genome
appears to be connected together in some kind of
a transcriptional network."
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The Scientist : First pages of regulation "Encyclopedia"
http://www.the-scientist.com/news/home/53280/
The researchers found consistent differences
between histone modifications of promoters and
non-promoter functional elements like enhancers,
and they also discovered that transcription factors
are equally likely to bind downstream as upstream
of a target gene.
In general, many of the findings regarding
chromatin structure, histone modifications, and
transcription have been suggested by previous
studies, Schadt said, but the size and depth of the
ENCODE analyses provide "a tour-de-force,
integrated analysis of all that information and
[show] how an extensive annotation of the human
genome might work," he told Nature.
The consortium next combined new data from
various types of analyses -- including transcription,
DNA replication timing, chromatin accessibility,
and histone modifications -- and used
computational algorithms to look for patterns of
organization across the entire genome,
Stamatoyannopoulos said. They found that all of
these data sets confirm a patchwork pattern of
transcriptionally active and inactive domains,
Stamatoyannopouloss said. This pattern does not
differ much between different cell types. "This is a
very satisfying finding, because it indicates that
there's some global structure of the genome," he
added.
One of the project's most novel findings, Schadt
and Mortlock agreed, is that about half of noncoding
functional elements do not appear to be
under evolutionary constraint, not only in humans,
but across multiple mammalian species. (The
researchers compared these regions with
orthologous regions of 14 mammalian genomes.)
Some researchers have suggested novel regulatory
elements can be discovered by simply looking for
conserved non-genic sequences between or within
species, Stamatoyannopoulos said, but this result
suggests that discovering them "really requires an
experimental approach."
If these regulatory regions are variable between
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The Scientist : First pages of regulation "Encyclopedia"
individual humans, they could be responsible for
"common variations in disease and drug responses,"
Schadt told Nature. "I think it will be one of the
more interesting things to explore" from the
project's findings, he said.
Melissa Lee Phillips
mail@the-scientist.com
Links within this article
C. Choi, "Regulatory DNAs may be missed," Nature,
March 24, 2006.
http://www.thescientist.com/news/display/23246/
L. Pray, "Post-genome project launches," Nature,
March 5, 2003.
http://www.thescientist.com/article/display/21158
The ENCODE Project Consortium, "Identification
and analysis of functional
elements in 1% of the human genome by the
ENCODE pilot project," Nature, June 14, 2007.
http://www.nature.com/nature
Eric Schadt
http://www.rii.com/about/executives.html
M.L. Phillips, "Non-coding DNA adapts," Nature,
October 20, 2005.
http://www.thescientist.com/article/display/22805/
John Stamatoyannopoulos
http://www.gs.washington.edu/faculty/stamj.htm
Genome Research
http://www.genome.org/
http://www.the-scientist.com/news/home/53280/
Douglas Mortlock
http://phg.mc.vanderbilt.edu/content/mortlock
J. Cheng et al., "Transcriptional maps of 10 human
Page 4 of 5
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The Scientist : First pages of regulation "Encyclopedia"
© 1986-2007 The Scientist Privacy Policy
chromosomes at 5-nucleotide resolution," Science,
May 20, 2005.
http://www.the-scientist.com/pubmed/15790807
Comment on this news story
http://www.the-scientist.com/news/home/53280/
Page 5 of 5
6/13/2007

NEWS OF THE WEEK
1556
GENOMICS
DNA Study Forces Rethink of
What It Means to Be a Gene
Genes, move over. Ever since the early 1900s,
biologists have thought about heredity primarily
in terms of genes. Today, they often view
genes as compact, information-laden gems
hidden among billions of bases of junk DNA.
But genes, it turns out, are neither compact nor
uniquely important. According to a painstaking
new analysis of 1% of the human
genome, genes can be sprawling, with farflung
protein-coding and regulatory regions
that overlap with other genes.
As part of the Encyclopedia of DNA
DNA work. For Ewan
Birney, coordinating
300 authors to analyze
1% of the human
genome (graphic, blue
bars) was a rewarding
challenge.
Elements (ENCODE) project, 35 research
teams have analyzed 44 regions of the human
genome covering 30 million bases and figured
out how each base contributes to overall
genome function. The results, compiled in a
paper in the 14 June issue of Natureand 28 papers
in the June issue of Genome Research, provide
a litany of new insights and drive home how
complex our genetic code really is. For example,
protein-coding DNA makes up barely
2% of the overall genome, yet 80% of the bases
studied showed signs of being expressed, says
Ewan Birney of the European Molecular Biology
Laboratory’s European Bioinformatics
Institute in Hinxton, U.K., who led the
ENCODE analysis.
Given the traditional gene-centric perspective,
that finding “is going to be very disturbing
to some people,” says John Greally, a molecular
biologist at Albert Einstein College of
Medicine in New York City. On the other hand,
says Francis Collins, director of the National
Human Genome Research Institute (NHGRI)
in Bethesda, Maryland, “we’re beginning to
understand the ground rules by which the
genome functions.”
Once the human genome sequence was in
hand by 2003, NHGRI set up ENCODE to
learn what those 3 billion or so bases were all
about. The initial 4-year, $42 million effort,
which tackled 1% of the human genome,
brought new and existing experimental and
computational approaches to bear, mapping
not just genes but also regulatory DNA and
other important features such as gene start
sites. NHGRI now plans to spend about
$23 million annually over the next 4 years to
perform a similar analysis of the whole
genome, expecting that the lessons learned
from the pilot ENCODE and new sequencing
technologies will greatly reduce the costs of
this extended project (Science, 25 May,
p. 1120). “The goal is to measure all the different
kinds of features across the human genome
and ask which features go together to understand
the whole package,” says George Weinstock,
a geneticist at Baylor College of Medicine in
Houston, Texas.
A key component of the pilot ENCODE is
an analysis of the “transcriptome,” the repertoire
of RNA molecules that cells create by
transcribing DNA. For protein-coding genes,
most of their RNA transcripts—the messenger
RNA (mRNA)—get translated into
15 JUNE 2007 VOL 316 SCIENCE www.sciencemag.org
Published by AAAS
chains of amino acids by ribosomes. For other
types of “genes,” RNA is the end product:
Ribosomal RNAs become the backbone of
the ribosome, for example.
Researchers used to think very little RNA
was produced beyond mRNA and a smattering
of RNA end products. But about half the transcripts
that molecular biologist Thomas Gingeras
of Affymetrix Inc. in Santa Clara, California,
discovered in his RNA survey 2 years ago
didn’t fit into these categories (Science,
20 May 2005, p. 1149), a finding ENCODE
has now substantiated. The ENCODE
researchers knew going in that the DNA they
were studying produced about eight nonprotein-coding
RNAs, and they have now discovered
thousands more. “A lot more of the
DNA [is] turning up in RNA than most people
would have predicted,” says Collins.
ENCODE has produced few clues as to
what these RNAs do—leaving some to wonder
whether experimental artifacts inflated the percentage
of DNA transcribed. Greally is satisfied
that ENCODE used enough different
techniques to show that the RNA transcripts
are real, but he’s not sure they’re biologically
important. “It’s possible some of these transcripts
are just the polymerase [enzyme] chugging
along like an Energizer bunny” and transcribing
extra DNA, he suggests.
But in the 8 June issue of Science (p. 1484),
Gingeras and his colleagues reported that
many of the mysterious RNA transcripts found
as part of ENCODE harbor short sequences,
conserved across mice and humans, that are
likely important in gene regulation. That these
transcripts are “so diverse and prevalent across
the genome just opens up the complexity of
this whole system,” says Gingeras.
▲
CREDITS (LEFT TO RIGHT): PHOTOLAB AT EMBL; GALT BARBER/UCSC

CREDIT: MICHAEL NAGLE/GETTY IMAGES
The mRNA produced from protein-coding
genes also held surprises. When Alexandre
Reymond, a medical geneticist at the University
of Lausanne, Switzerland, and his colleagues
took a close look at the 400 proteincoding
genes contained in ENCODE’s target
DNA, they found additional exons—the
regions that code for amino acids—for more
than 80%. Many of these newfound exons were
located thousands of bases away from the
gene’s previously known exons, sometimes
hidden in another gene. Moreover, some
mRNAs were derived from exons belonging to
two genes, a finding, says Reymond, that
“underscores that we have still not truly
answered the question, ‘What is a gene?’ ” In
addition, further extending and blurring gene
boundaries, ENCODE uncovered a slew of
novel “start sites” for genes—the DNA
sequences where transcription begins—many
located hundreds of thousands of bases away
from the known start sites.
Before ENCODE started, researchers knew
of about 532 promoters, regulatory DNA that
helps jump-start gene activity, in the human
DNA chosen for analysis. Now they have
775 in hand, with more awaiting verification.
Unexpectedly, about one-quarter of the pro-
moters discovered were at the ends of the genes
instead of at the beginning.
The distributions of exons, promoters, gene
start sites, and other DNA features and the existence
of widespread transcription suggest that a
multidimensional network regulates gene
expression. Gingeras contends that because of
this complexity, researchers should look at
RNA transcripts and not genes as the fundamental
functional units of genomes. But
Collins is more circumspect. The gene “is a
concept that’s not going out of fashion,” he predicts.
“It’s just that we have to be more thoughtful
about it.” –ELIZABETH PENNISI
SYNTHETIC BIOLOGY
Attempt to Patent Artificial Organism Draws a Protest
An activist group’s concern about maverick
genome sequencer J. Craig Venter’s intention
to patent an entirely synthetic free-living
organism has thrown a spotlight on the emerging
intellectual-property landscape in this hot
new field. The protesters claim that Venter
wants his company to become the Microsoft
of synthetic biology, dominating the industry.
Venter hopes to use the artificial life form,
which he says does not yet exist, as a carrier
for genes that would enable the bug to crank
out hydrogen or ethanol to produce cheap
energy. Duke University law professor Arti
Rai says the patent, if awarded, “could be
problematic” only if Venter’s product became
the standard in the field. But Venter says this
application is just the start: He plans to patent
methods that would cover more than the single
microbe described in the application.
“We’d certainly like the freedom to operate on
all synthetic organisms” that could serve as a
chassis for swapping out genes, says Venter,
whose research team is at the nonprofit
J. Craig Venter Institute in Rockville, Maryland,
but who recently started a company to
commercialize the work.
Filed last October and published by the
U.S. Patent and Trademark Office on 31 May,
the application describes “a minimal set of
protein-coding genes which provides the
information required for replication of a freeliving
organism in a rich bacterial culture
medium.” The application cites work by
Hamilton Smith and others on Venter’s team
on a simple bacterium called Mycoplasma
genitalium that they are using to determine
the minimum number of genes for life. They
want to synthesize this “minimal genome”
from scratch, get it working inside a cell, then
add genes to produce cheap fuels (Science,
14 February 2003, p. 1006).
In a press release, the ETC Group, a technology
watchdog in Ottawa, Canada, called
Venter’s “monopoly claims … the start of a
high-stakes commercial race to synthesize and
privatize synthetic life forms.” ETC calls for
the U.S. and international patent offices to
reject the patent so that societal implications
can be considered. ETC also cited a recent
Newsweek interview in which the scientist
says he wants to create “the first billion- or
trillion-dollar organism.”
Venter says this is just one of several patent
applications that would give his company,
Synthetic Genomics Inc., exclusive rights to
methods for making synthetic organisms. The
artificial Mycoplasma “may or may not be”
the one used to generate hydrogen or ethanol,
Future monopoly?
Craig Venter wants
to patent methods
for making synthetic
organisms.
NEWS OF THE WEEK
he says; his team is working on several
species. “We haven’t given any thought to” the
licensing conditions, but in any case, they
would not impede work in academic labs, says
Venter, adding, “This is a problem that we
hope will have hundreds of solutions.”
Rai says the notion that Venter’s Mycoplasma
strain will dominate the way Microsoft’s Windows
did is tenuous because “about 10 things
would have to happen,” among them that Venter
would create the organism, get the patent, and
others would adopt his technology as the standard.
Even if that happened, Venter “could do
well [financially] and do good,” she says, by
licensing the technology at low cost as a
research tool, as happened with the original
patents on recombinant DNA technology.
Other synthetic biologists don’t seem
fazed. “He’s shooting an arrow in the general
direction that things are going,” says Frederick
Blattner of the University of Wisconsin,
Madison, who has patented a stripped-down
Escherichia coli and founded a company
called Scarab Genomics that is commercializing
the technology while disbursing it to academic
researchers for a small cost. The more
pertinent question, says Harvard’s George
Church, is whether the inventors’ claims to
have devised something useful will hold up,
as there’s no obvious reason why a completely
synthetic Mycoplasma is needed rather than,
say, modified E. coli to make hydrogen.
Massachusetts Institute of Technology
synthetic biologist Tom Knight, who has
pointed out that anyone could get around the
patent simply by adding more than the
450 genes stipulated, says his complaint is
that the application doesn’t explain how to
build the artificial cell. “I think it’s rather
tasteless,” Knight says.
–JOCELYN KAISER
www.sciencemag.org SCIENCE VOL 316 15 JUNE 2007 1557
Published by AAAS

Wired Science - Wired Blogs
« Atlantis Crew Completes Second Spacewalk | Main | International Space Station Computers Restored »
Your Genome is Really, Really, REALLY Complicated
By Brandon Keim June 14, 2007 | 10:22:58 AM Categories: Genetics
The ninety-five percent of the human genome that doesn't actively code for proteins and
was historically known as "junk" DNA is actually vital for regulating the activities of that
remaining five percent.
Those are the findings of researchers collaborating on the Encyclopedia of DNA
Elements, or ENCODE. The concept isn't exactly new -- quite a few scientists have long
felt that evolution didn't keep nine-tenths of the genome around just because it couldn't
be bothered to take out the trash -- but the researchers charted the nether regions of our
genome with unprecedented detail.
The ENCODE findings, derived from studying a small part of the genome and due to be scaled up in coming years, foreshadow
profound refocusing of our current low-resolution understanding of human genetics. Which isn't to say that earlier genetic
research is irrelevant: all those isolated gene findings, those associations of genes with proteins, of mutations with disease, are
important pieces of the puzzle. In some cases -- as with Tay-Sachs disease and Huntington's syndrome -- they're extremely
useful. But the findings do show just how preliminary our understanding of genetics is.
Since inveigling against genetic reductionism is an old hobby of mine, it's nice to see the genome's complexity getting some
overdue recognition. Not that this is big news to some scientists, but it's a revelation to the public at large. Indeed, the news
articles surrounding the ENCODE findings capture this well:
BBC: The study, which was carried out on just 1% of our DNA code, challenges the view that genes are the
main players in driving our biochemistry.
Boston Globe: Genes, it turns out, may be relatively minor players in genetic processes that are far more subtle
and complicated than previously imagined.
Guardian: The findings highlighted how scientists had become so blinded by the importance of genes that the
role of other parts of the genome had largely gone unappreciated....
Agence France-Presse: The most detailed probe yet into the workings of the human genome has led scientists
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Wired Science - Wired Blogs
to conclude that a cornerstone concept about the chemical code for life is badly flawed.
ABC: The study brings a new dimension to determining both the impact of human genetics in clinical medicine
and how humans evolved differently from animals.
For years, the public has been treated to a neverending stream of pronouncements surrounding the potential insights and
therapies that will follow from the finding of a gene or two associated with some disease or behavior. Science journalists are, by
and large, the people who've carried these findings to the public. This is understandable: they take their lead from journals and
the scientific PR machine. But from the latest round of news articles, it should follow that simplistic narratives of genes and
disease are at an end.
Let's see just how long that lasts....
Related Wired coverage here.
Image: Ami Shah
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LexisNexis(TM) Academic - Document
Search Terms: genome
LENGTH: 2438 words
HEADLINE: Reading Between the Genomes
ANCHORS: IRA FLATOW
BODY:
IRA FLATOW, host:
Copyright 2007 National Public Radio (R)
All Rights Reserved
National Public Radio (NPR)
SHOW: Talk of the Nation: Science Friday 2:00 PM EST
June 15, 2007 Friday
And now, we're changing gears for the rest of the hour - reading between the genes. When scientists first
began to decode the human genome, the big news was and still is, in many ways, the genes, parts of the
DNA that held the blueprint for creating all our parts of our bodies or malfunction to create disease. And the
race was on to find the genes that cause diabetes or cancer or depression. The bits between the genes, the
repeating sequences that didn't seem to do anything, were referred to as junk DNA and not really worth
anything.
But the genes, it turns out, make up only a small part of the genome, and scientists are learning that much
of that so-called junk DNA may play a major role in regulating how the not-junk DNA or regular DNA is
expressed. And this week, a consortium of researchers from around the world released a study looking at a
sample of that junk DNA. And joining me now to talk about what they found is John M. Greally - he is
assistant professor at Albert Einstein College of Medicine in the Bronx, and he's here with in our New York
studio. Thank you for coming in today.
Dr. JOHN M. GREALLY (Epigenomics and Human Disease, Albert Einstein College of Medicine): Thanks for
inviting me.
FLATOW: So the junk is not really junk after all?
Dr. GREALLY: It'd be a very brave person who would call it junk at this stage.
FLATOW: Why?
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Dr. GREALLY: Well, even before this study, when people were looking at small areas of the genome, the
regions that were neighboring the genes that we knew were doing functional things like producing the red
pigment in our red cells to carry oxygen - what they realized was that there were - some of these sequences
that were not genes were actually responsible for switching on or off the gene expression. So we knew that it
wasn't all junk, but this is the first study to kind of formally look at a large region of the genome and be
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systematic in research.
FLATOW: And did you discover that that was the function of the so-called junk DNA, switching the other DNA
on and off?
Dr. GREALLY: They found a lot of different things in this particular study, but possibly the most interesting
one was the ability of the DNA that was neighboring the genes to have a regulatory role. There are - it seems
like there's a lot more happening in the genome than just the expression of these genes.
FLATOW: And this is most of what's in the genome (unintelligible)...
Dr. GREALLY: That's exactly right.
FLATOW: Give us some idea of how much of it is not that normal DNA we think of.
Dr. GREALLY: Well, if you were to try to visualize this, it would be like driving on a highway. And every time
you pass an exit, it's like a snippet of the gene, an exon of a gene as we'd call it. Most of the time, we're on
the highway; we're not at exits. And in fact, the genome is very like that. About 96 percent, conservatively,
of the genome is not genes, so it's a little bit of a shock, I think to realize just how much of it is stuff that we
don't understand.
FLATOW: Would this switching function and the presence of this other kind of DNA explain things that we've
seen everyday life but really couldn't, you know, explain before about how things work, like why somebody
gets a disease while somebody does not get disease.
Dr. GREALLY: Yeah. There are a couple of ways of looking at this. One is that these sequences that sit
between the genes or beside the genes are determining which genes should be switched on or off in a specific
cell type because the DNA itself is the same in a liver cell or a muscle cell or a brain cell, but the exact
repertoire of genes that we switch on or off in each of those cell types differs. And those instructions are
mediated by these sequences that live nearby.
In terms of disease, that - this is where it gets very interesting - because some of the recent studies that
were performed, for example, to look at large numbers of patients with adult diabetes, they realized that
there were certain genes that looked like they were associated with the disease, but when you look at their
results, you realize that a lot of the changes that they were seeing in the DNA sequence were not in the
genes themselves, they were nearby.
And it's - you know that those sequences are very associated with diabetes. You're much more likely to see it
in a diabetic individual than somebody else. But the precise function, the way that it might be causing the
diabetes, is still a mystery.
FLATOW: Do we have a name for this DNA, instead of calling it none or other or something? Have scientists
given these genes a name and the sequences or these parts?
Dr. GREALLY: It depends on their function, and this particular study didn't really try to assign a function to
the sequences. The study was really to try to identify the subset of this 96 percent that might be doing
something functionally. When you start studying these in more detail, which would presumably be a follow-up
study, some of these sequences act to increase the local gene expression, and they would be known as
enhancers.
Others tend to dampen down local gene expression. They would be known as silencers or perhaps repressors.
And there are others that have this amazing property where if you have two genes side by side and you want
to regulate them independently, the sequence in between will actually act as an insulator, and that's how
they are referred.
FLATOW: Could these genes - whatever we're calling them now - might have great influence in early
embryology?
Dr. GREALLY: Absolutely.
FLATOW: I mean, things on and off - might that be a good place to study what they do?
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Dr. GREALLY: Yes, definitely. Yeah.
FLATOW: Yeah.
Dr. GREALLY: It's already known that there are huge changes in the expression of genes during early
development. There have been human malformation syndromes - things where children have been born with,
you know, limb problems or problems with the - the formation of their brain - where the events have
occurred out in the wilderness between the genes but not in the genes themselves. So clearly, that is going
to be a very important area.
FLATOW: But we inherit these as the same way we inherit the other.
Dr. GREALLY: It all comes as one package, one long string of DNA. It has all the intervening stuff and the
genes.
FLATOW: And so this may add a whole new layer of complexity; things are not as simple as we thought they
used to be.
Dr. GREALLY: Absolutely. And a further layer of complexity is when you impose epigenetics on top of that,
which is an area of interest to a lot of people at the moment.
FLATOW: Well, explain what that is.
Dr. GREALLY: Yeah. What the ENCODE guys were doing - the consortium was doing - they were looking to
see where the sequences are located that might be doing something. But having found those sequences, the
- something has to mediate their role, and the broad group of regulatory mechanisms, biochemical
mechanisms that do something to those sequences, have been loosely referred to as epigenetic.
And what can happen at those sites is that sometimes, the epigenetic regulators can have one pattern that
might be associated, perhaps, with strong activation of a gene nearby. And sometimes, it may have a
different pattern where it may actually have exactly the opposite effect. And the reason that this becomes
particularly interesting is that it's this epigenetic regulation that is our means of responding to the
environment and to noxious stimuli and basically reorganize the way that we express genes in a way that will
allow us to adopt to our environment.
FLATOW: What does this mean for genetic testing? We do genetic testing - there are home genetic kits
coming on the market. We're in an era where now we know what your genome is. Doesn't that make these
genetic tests really inadequate? Because it may show you you have the gene, but we may not know if it gets
- ever gets switched on or not by another gene.
Dr. GREALLY: If you have a mutation in a gene, the gene is dead or the gene has got a problem. So it doesn't
matter if the local regulatory mechanisms are acting inappropriately or not. Thinking very simplistically, you
can put gas in the tank, you can put new brake pads on, but if the engine is blown, it's not going to go
anywhere. And the engine, in this case, would be the gene, so it doesn't matter what you do nearby.
However, in terms of the issue of DNA testing, what it does is it broadens the opportunities available to us. It
may be that we are able to start focusing on these sequences that have regulatory functions in between the
genes, look for the sequence changes that are occurring there, and actually be able to understand that they
are as important as the changes in the genes and thus be able to do something predictive and accurate with
our patients.
FLATOW: So you'd have to look to those also. You just couldn't say you have this gene for, let's say, breast
cancer or something. And you - you have to have the activator gene that might also turn on or switch it off.
Dr. GREALLY: Well, the...
FLATOW: That may be a bad example because of the...
Dr. GREALLY: Yes.
FLATOW: PrCA(ph).
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Dr. GREALLY: It's actually not a bad example in term of another type of cancer, which is colon cancer. There
are some familial cases of colon cancer where these are very unfortunate families. The individuals get a very
difficult type of cancer to diagnose, and they get it early in life, and it's called hereditary nonpolyposis colon
cancer. And that is due to mutations, generally, in a gene called MLH1.
But recently, there was a very intriguing report where the gene was perfectly healthy. There was no mutation
in either copy of the gene that this individual had. But what they had instead was a change in the regulation
of the gene, so it was silenced. And it is important in this instance because it illustrates that silencing of both
copies of the gene is as devastating to the cell or to the body as mutations of both of those copies.
FLATOW: This is TALK OF THE NATION: SCIENCE FRIDAY from NPR News. I'm Ira Flatow, talking with John
Greally, assistant professor at the Albert Einstein College of Medicine in the Bronx. So we're talking about
rethinking the human genome with these - with these genes, these helper genes, the switcher genes, all
kinds of genes. Well, maybe our listeners will come up with a name for what we can call the whole group of
genes. Let's go to Jessica in Denver. Hi, Jessica.
JESSICA (Caller): Hi. Nice to be on the show.
FLATOW: Hi. Thank you.
JESSICA: I was just going to point out that the idea there may have been junk DNA in the first place seems
quite absurd to me. It seems as if shortly after the genome was mapped, that James Watson has formulated
some sort of language for the genome, and it was quite simple at first. But after a year of the scientific
discovery, we have discovered that the genome can play a lot of tricks on us, that things aren't initially what
they first appear. And we are still discovering things like that every day. It seems like most mappings of the
genome play a very important part in the human body.
FLATOW: Dr. Greally?
Dr. GREALLY: Jessica, I think it's a fair point that there's a lot more complexity to the genome than we have
realized up to now. I think even Dr. Watson was probably surprised at how little of the genome-encoded
genes and - you know, we've had to deal with that in terms of our emotional well-being. But at the end of the
day, the challenge is not to throw our hands up and say we don't understand the challenges, to say all of this
material is out there in the genome. It's there to be understood. Let's tackle the problem. And that's what
this - that's why this recent publication was such a landmark that these guys went after it systematically.
FLATOW: Well, you bring up a good point. If only just a few percentage of the genome encodes for genes,
and let's say 95 - could be a 98 - yeah, 95 percent of it is these other kinds of genes?
Dr. GREALLY: Other kinds of sequences.
FLATOW: Sequences.
Dr. GREALLY: Yeah.
FLATOW: And we haven't encoded those?
Dr. GREALLY: We haven't figured...
FLATOW: And we haven't - so we haven't figured - it's like the universe. We don't know what 95 percent of
the universe is. We don't know what 95 percent of this other dark - it's called the dark genes, you know?
Dr. GREALLY: People have referred to it as the dark matter, the genome.
FLATOW: Yeah. So our work has just begun.
Dr. GREALLY: It's a good thing if you're - if you're in this line of business.
(Soundbite of laughter)
FLATOW: I mean, here we've been celebrating the deciphering of a human genome, but we haven't
deciphered now, and now we see how important to know what it is - 95 percent of the genome.
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Dr. GREALLY: If we didn't have the Human Genome Project, we wouldn't have this problem. So the Human
Genome Project was a great foundation for discovery. And now, we're going to take that one step further.
FLATOW: What made this breakthrough possible?
Dr. GREALLY: The usual combination, intellectual curiosity and technology. It would have been very difficult
to do this about 10 years ago. But there have been advances in technology that allow you to look at lots and
lots of DNA sequences simultaneously, and particularly in areas such as microarray technology which is quite
popular in the field at the moment. And because of the fact that people start to get clever about how they
could use these microarrays and sequencing technologies, that, in particular, was a breakthrough.
FLATOW: Was there one sequence that lit a light bulb up in someone's head and said, whoa - we can't
explain it any other way but these dark genes?
Dr. GREALLY: There - not in this particular project. This particular project was most notable for the sheer
number of sequences it was pulling in simultaneously. So we have a bit of information overload to deal with.
FLATOW: And so now, the work will go on to decipher.
Dr. GREALLY: Absolutely.
FLATOW: Are there any - could - how long do you think it would take? How many years?
Dr. GREALLY: Well, through my retirement, I guess.
(Soundbite of laughter)
FLATOW: You're going to look very old. There's other - there's a lot of work to be shared and done by
everybody.
Dr. GREALLY: Absolutely. But it's an accelerating pace, so being a typical, cautious scientist, I'm not going to
put a number on it.
FLATOW: And we won't force you. Thank you for taking time to be with us.
Dr. GREALLY: Thank you for inviting me.
FLATOW: John M. Greally is assistant professor at the Albert Einstein College of Medicine right here in the
Bronx in New York.
(Soundbite of music)
FLATOW: Have a great weekend. I'm Ira Flatow in New York.
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ENCODE finds the human genome to be an active place
Sequence Search Paper
10 mistakes to avoid before you
run your next Gene Sequence
Search.
www.genomequest.com
ENCODE finds the human genome to be an active place
By John Timmer | Published: June 13, 2007 - 12:28PM CT
Biblical Adam, First Man
Adam, first man per Bible records,
archaeology dates him to 14,000
BP
www.accuracyingenesis.com
A paper that will appear in today's edition of Nature starts off with a bang, its first sentence
being "The human genome is an elegant but cryptic store of information." The paper's goal is
nothing less than decrypting as much as we can about a one percent of that genome, in the
expectation that it will serve as an accurate model of the remaining 99 percent. It's an
audacious and very satisfying piece of work; my biggest qualm about it comes from the
accompanying press releases, which suggest that we're going to see some bafflingly incoherent
media coverage of the findings.
ENCODE stands for Encyclopedia of DNA Elements, and it is a multi-institutional consortium
dedicated to finding out what our DNA is up to. As a first step, 30 Megabases of DNA from 44
different locations in the genome were subjected to roughly 200 forms of biochemical and
computational analysis. These methods explored RNA production, DNA packaging, and other
aspects by several independent assays, providing a fair degree of confidence in the results.
A genome full of pervasive transcription
The big surprise in this work is that the genome is pervasively made into RNA. Although the
view that RNA's primary function is to code for proteins went by the wayside with the discovery
of various forms of regulatory RNA, the regulatory RNAs still fit into the paradigm of consistent
and discrete RNA production. The new study finds that essentially every base in the genome
shows up in RNA at one point or another. This is despite the fact that most of these bases
aren't doing anything: 95 percent of the genome isn't under selective pressure, and most of
that 95 percent doesn't appear functional in an evolutionary sense.
The data indicate that the process of copying DNA into RNA, called transcription, is
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6/13/2007

ENCODE finds the human genome to be an active place
fundamentally noisy. The transcription factors that tell the cell where to start making RNAs are
rather promiscuous, often having affinities for DNA sequences that will appear at random every
1,000 bases. They also act against a background where the packaging of DNA in the cell, which
determines their access to such sequences, is dynamically changing. Apparently, wherever
these changing conditions allow, transcription will start.
This suggest that regulatory elements around genes act less to specifically start transcription
there and more to make gene transcription at the gene more probable than the general
background of RNA noise. That said, the study also found clear signals of defined transcription
start sites at a rate of nearly ten times the number of genes in the area, suggesting some
aspects of the excess transcription are nonrandom. Other examples of extra transcribed bases
result from a transcription stopping mechanism that also appears to be noisy. In several cases,
RNAs were found that started in one gene and plowed straight through to the next one down
the chromosome.
The study did find one factor that might explain the distribution of all the extra sites of
transcription when it looked into the process of duplicating the DNA prior to cell division. Areas
where this process starts appear to have less compact DNA, which favors transcript initiation as
well.
If there's a weakness to this study, it's that it used cells that grow rapidly in culture instead of
samples from normal tissue. These cultured cells generally have origins in cancer and so may
have aberrant control of a range of cellular processes. Hopefully, the study can be repeated
using cells that are a better approximation of normal.
Where does this leave us?
There seems to be three possible interpretations for all these extra transcripts. One is that,
even though we haven't detected a biological function, and evolution doesn't conserve them,
they are actually specifically functional. This would be the "there is no junk DNA" take on
matters. The opposite extreme would be an "it's all junk" view of it. From this perspective, the
starting and stopping of transcription is just an inherently noisy process and doesn't do humans
enough harm to create a selective pressure to improve it.
Somewhere between the two would be the view that few of these extra transcripts are useful in
themselves, but it's useful having them present on the collective level. Reasons could include
anything ranging from excess RNA performing some sort of structural function through to the
random transcripts being a rich source of new genes.
Personally, I fall into the "it's all junk" end of the spectrum. If almost all of these sequences are
not conserved by evolution, and we haven't found a function for any of them yet, it's hard to
see how the "none of it's junk" view can be maintained. There's also an absence of support for
the intervening view, again because of a lack of evidence for actual utility. The genomes of
closely related species have revealed very few genes added from non-coding DNA, and all of
the structural RNA we've found has very specific sequence requirements. The all-junk view, in
contrast, is consistent with current data. We've wondered for decades how transcription factors
can act specifically and at long distances despite their relatively weak specificity for DNA. This
data answers that question simply: they don't.
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ENCODE finds the human genome to be an active place
All of this brings me back to the press release, which has set my blood boiling nearly every time
I read it. It basically takes the hardcore "none of it is junk" view but then undercuts its own
arguments. It states that "the new data indicate that the genome contains very little unused
sequences; genes are just one of many types of DNA sequences that have a functional impact."
What is that functional impact? They have no idea: "many species' genomes contain a pool of
functional elements that provide no specific benefits in terms of survival or reproduction."
It looks like they're choosing to define functional as "made into RNA," even though they
recognize that much of the DNA that is made into RNAs clearly has no influence on survival or
fitness. They're then using that skewed definition to claim the data shows that most of the
genome is functional. Since most of the popular press produces accounts based on the press
release, the public is going to be receiving a very distorted view of this work.
Filed under: RNA, DNA, Transcription, Genomics, more...
Reader comments
Walshicus
How much CPU power are we talking about to simulate this kind of thing? Beyond the
scope of a large distributed net?
June 13, 2007 @ 01:23PM
hoottwo
I think I fall into the "all junk" camp. Was this a steady state analysis? It may be that
none of this extra transcribed junk is stable enought to be of any use. In other words,
only complete RNAs remain stable long enough to be translated or used structurally.
June 13, 2007 @ 01:36PM
name99
Do we know enough to say that that transcribed RNA just sits around randomly until it is
later broken into pieces? As opposed to, for example,
• acting as ribozymes
• acting as second order transcription factors
• (this is the most interesting one) acting as a store of parts --- ie the resultant long
tRNAs are broken into smaller pieces that are useful in various ways, and because this
isn't a very demanding process, there isn't much selection pressure. This is your
intermediate view.
Damn, this opens up so many questions.
Obviously just creating RNAs to then destroy them wastes energy. My understanding of
prokaryotes is that, as a corollary to the fact that they don't have exons/introns, they
don't have what is called junk DNA So that's no help But do we get this same behavior
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ENCODE finds the human genome to be an active place
not afford to be simply creating then destroying RNA without it having some important
side effect.
rmongiovi
June 13, 2007 @ 01:59PM
Sounds like it's a question of your definition of "functional". If all DNA makes some sort
of RNA, then it's definitely functional.
To borrow an analogy from the computer world - it's all data, but it's not all information.
June 13, 2007 @ 02:32PM
IdeaHamster
Actually, this sounds a lot like some results that I heard about a while back with E. coli
(don't know if they were ever published, hence the lack of linkage...guess you'll just
have to trust me ). Basically, if you turn the sensitivity of an E. coli genomic
microarray all the way up, you find that every base on both strands ends up getting
translated at some basal level. So, this sort of leeds credence to the "just junk/noise"
argument.
On the other hand, one theory I've always liked is the idea that these stretches can
serve as emergency gap fillers during DNA damage, or even as templates for
recombinative repair mechanisms...but then you would expect the expression to be
much less random. So, maybe I do fall in the "just junk" camp after all?
EDIT: As for the press release...
If I do end up leaving science...and trust me, as a former 6 y.o. kid obsessed with his
Fischer-Price microscope, leaving science is not something I want to do...but if I do it will
be because of the "Hollywoodification" of research.
June 13, 2007 @ 02:35PM
Copyright © 1998-2007 Ars Technica, LLC
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6/13/2007

Chemical & Engineering News: Latest News - Finding Function In The Genome
Chemical & Engineering News
Latest News
June 13, 2007
Genomics
Finding Function In The Genome
Consortium uncovers surprising features in the human
genetic blueprint
Amanda Yarnell
Page 1 of 2
Following on the heels of the massive Human Genome Project, which revealed the sequence of the human
genome, a huge consortium of scientists has unveiled its preliminary progress in analyzing the functions of
various stretches of that genetic blueprint (Nature 2007, 447, 799 and entire issue of Genome Res. 2007, 17).
Vernon Doucette/Boston University
ENCODE consortium members Tullius (from right) and graduate students Stephen Parker and Eric Bishop use a
capillary DNA sequencer to determine DNA cleavage patterns that provide information about the shape of the
DNA backbone
Participants in the ENCODE (Encyclopedia of DNA Elements) project devised and tested a wide variety of highthroughput
experimental and computational methods for identifying functional elements in a representative
fraction of the genome. Such functional elements include sequences that code for proteins, sequences that don’t
code for proteins, regulatory sequences that control the transcription of DNA, and sequences that control the
packaging of the genome.
The consortium’s effort has revealed quite a few surprises about the genomic landscape. For instance, the team
reports that the majority of DNA—whether it encodes proteins or not—is transcribed into RNA. This pervasive
pattern of transcription challenges the longstanding notion that the human genome consists of a relatively small
number of discrete genes surrounded by a plethora of seemingly irrelevant "junk" DNA, the say.
"We are increasingly being forced to pay attention to our nongene DNA sequences," notes John M. Greally of
Albert Einstein College of Medicine in a commentary in Nature accompanying the consortium’s report. He adds
that the consortium’s observations follow recent reports that many single-nucleotide genomic variations
associated with disease are found outside of genes.
Also, contrary to conventional wisdom, about half of the functional elements identified by consortium scientists
http://pubs.acs.org/cen/news/85/i25/8525news4.html
6/13/2007

Chemical & Engineering News: Latest News - Finding Function In The Genome
appear to have been under little or no evolutionary constraint. That is, their sequences don’t seem to be
conserved across different species. One possible explanation for this observation comes from Boston University
chemistry professor and consortium member Thomas Tullius, whose lab is surveying the local DNA-backbone
structure of functional elements in the genome (Genome Res. 2007, 17, 940 and 947). "Maybe sequence isn’t the
final answer," he says. "I suspect we might find that the structure, not the sequence, of these functional elements
is, in fact, what’s been conserved during evolution."
The consortium’s first-stage report covers 1% of the human genome, or roughly 30 million base pairs, selected to
give a representative cross-section of the genetic blueprint. In the future, its members hope to produce a
comprehensive catalog of all functional elements in the human genome.
"The glimpse we are provided by the ENCODE consortium into the ordered complexity of 1% of the human
genome is tantalizing," Greally notes. But, he adds, it remains to be seen whether the researchers’ findings during
the pilot phase will extend to the other 99% of the human genome. Consortium scientists face not only the work o
scaling up the project’s methods but also the challenge of proving that their insights, obtained from easy-to-culture
human cell lines, are representative of the many different types of primary cells found in the human body.
In the meantime, "because of the hard work and keen insights of the ENCODE consortium, the scientific
community will need to rethink some long-held views about what genes are and what they do, as well as how the
genome’s functional elements have evolved," comments Francis S. Collins, director of the National Human
Genome Research Institute at the National Institutes of Health in Bethesda, Md. "This could have significant
implications for efforts to identify the DNA sequences involved in many human diseases."
Chemical & Engineering News
ISSN 0009-2347
Copyright © 2007 American Chemical Society
http://pubs.acs.org/cen/news/85/i25/8525news4.html
Page 2 of 2
6/13/2007

Human Genome Not So Tidy After All, ENCODE Project Suggests
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Human Genome Not So Tidy After All, ENCODE Project Suggests
[June 13, 2007]
By a GenomeWeb staff reporter
NEW YORK (GenomeWeb News) — The human genome may
not be a “tidy collection of independent genes,“ but rather “a
network in which genes, regulatory elements and other types
of DNA sequences interact in complex, overlapping ways,”
according to National Human Genome Research Institute,
which today announced the publication of results from its
ENCODE Project in the June issue of Nature, and 28
companion papers in Genome Research.
The ENCODE consortium, which comprises 35 groups from
80 organizations around the world, debuted in 2003 to build
a “parts list” of the biologically functional elements in 1
percent of the human genome, and is a pilot study meant to
“test the feasibility of a full-scale initiative to produce a
comprehensive catalog of all components of the human
genome crucial for biological function.”
In the papers, ENCODE partners describe “major findings” in
gene transcription and regulation, chromatin and replication,
and evolutionary constraint.
These findings include the discovery that the majority of DNA
in the human genome is transcribed into RNA, and that these
transcripts extensively overlap one another. “This broad
pattern of transcription challenges the long-standing view
that the human genome consists of a relatively small set of
discrete genes, along with a vast amount of so-called junk
DNA that is not biologically active,” NHGRI said in a
statement.
The data also showed that the human genome contains
“very little unused sequences” and is a “complex, interwoven
network.” According to NHGRI, in this network genes are
“just one of many types of DNA sequences that have a
functional impact.”
http://www.genomeweb.com/issues/news/140550-1.html
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Human Genome Not So Tidy After All, ENCODE Project Suggests
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In the Nature paper, the authors write, "Our perspective of
transcription and genes may have to evolve,” noting the
network model of the genome "poses some interesting
mechanistic questions" that have yet to be answered.
Other “surprises” in the ENCODE data could have “major
implications” in how researchers understand the evolution of
genomes, particularly mammalian genomes. “Until recently,
researchers had thought that most of the DNA sequences
important for biological function would be in areas of the
genome most subject to evolutionary constraint,” NHGRI
said.
However, the ENCODE effort found that about half of functional elements in the human
to have been obviously constrained during evolution, at least when examined by curren
computational biologists.”
According to the ENCODE researchers, this lack of evolutionary constraint may indicate
genomes contain a “pool of functional elements,” including RNA transcripts, that “provid
terms of survival or reproduction.”
Over time, this pool may serve as a "warehouse for natural selection" by acting as a “so
elements unique to each species and of elements that perform the similar functions amo
having sequences that appear dissimilar,” the researchers speculated.
Other ENCODE findings include the identification of numerous previously unrecognized s
transcription; the discovery of evidence that, contrary to traditional views, regulatory se
to be located downstream of a transcription start site on a DNA strand as upstream; the
signatures of change in histones, and correlation of these signatures with different geno
deeper understanding of how histone modification coordinates DNA replication.
The NHGRI said that taken together, these findings will “reshape our understanding of h
functions.”
The study focused on 44 targets, which together cover about 1 percent of the human ge
about 30 million DNA base pairs. The targets were selected to provide a representative
entire human genome. All told, the ENCODE consortium generated more than 200 datas
than 600 million data points.
NHGRI Director Francis Collins said the ENCODE effort has “blazed the way for future ef
functional landscape of the entire human genome.”
The main portal for ENCODE data is the University of California, Santa Cruz's ENCODE G
analysis effort is coordinated by Ensembl, a joint project of the European Bioinformatics
Wellcome Trust Sanger Institute.
Much of the primary data have been deposited in databases at the NIH's National Cente
Biotechnology Information and at EBI.
Additional information on the ENCODE project can be found here.
http://www.genomeweb.com/issues/news/140550-1.html
Page 2 of 2
Steven Verdooner, Rich
Kreatech Biotechnology
Mount Sinai Thoracic S
microRNA Profiles in Es
Qiagen, Digene, eXege
Copyright © 2007 GenomeWeb LLC. All rights reserved.
6/13/2007

TheStar.com - News - DNA `junk' appears to have uses
DNA `junk' appears to have uses
June 14, 2007
JOSEPH HALL
HEALTH REPORTER
A groundbreaking study says scientists may have to substantially alter
their long-held conception of life's basic blueprint, DNA.
In a departure from traditional thinking, the four-year study says that
genes can no longer be considered the only active parts of DNA and that
huge segments thought to be "junk" may play a significant role in such
individual traits as susceptibility to diseases.
"A lot of these regions that previously we were thinking were junk DNA, or
vast deserts of non-functionality, have been found to be a lot more active,"
says Steven Jones, associate director of the British Columbia Cancer
Agency's Genome Sciences Centre, and one of numerous authors of the
scientific paper published today in the journal Nature.
"This was the surprise ... they seem to be doing things from a biological
level."
Human DNA is made up of some 3 billion base pairs of nucleotides
arranged in a double helix. Genes, which carry the code for proteins
necessary to build a human, are arranged on the rungs of the twisted
ladder, but segments of DNA are interspersed that were previously
dismissed as little more than rubbish – evolutionary remnants that merely
gave structure to the ladder.
But the new study says many of these may, in fact, play an integral role in
controlling some of our genes and determining traits such as risk for type 2
diabetes.
"These might be regions ... that may be functional elements within our
genomes, but don't have the star status of the (genes)," Jones says.
http://www.thestar.com/printArticle/225245
Page 1 of 2
6/14/2007

TheStar.com - News - DNA `junk' appears to have uses
These segments might also be acting as a "warehouse" for genetic material
that could be critical for future evolutionary steps, says Ewan Birney, lead
author of the study and senior scientist with the European Molecular
Biology Laboratory in Hinxton, England.
"And then evolution can kind of tap into them when it needs to ..."
Dr. Rod McInnes, scientific director of genetics at the Canadian Institutes
of Health Research, who was not involved in the study, called the research
"transformative" and "stunning."
"It's absolutely fundamental stuff which is telling us things about the
genome ... that I don't think anybody realized before."
Jones says most of the DNA segments previously considered to be inactive
junk are busily "transcribing" messages through RNA.
This RNA molecule, a single-strand copy of DNA, allows a segment of DNA
to be translated into proteins.
It was long thought that only the gene segments of DNA, which is
separated into 23 chromosome pairings in humans, were sending out these
RNA messengers.
But it's not clear if this newly discovered RNA messaging is being heard
and, if so, where.
"They are not silent parts of the genome ... but whether they are useful is
the question that is outstanding," Birney says. He said it's possible many
are acting on various genes in "very subtle" ways.
The four-year-study was published in Nature by an international team of
genomic researchers known as ENCODE, on the occasion of the 50th
anniversary of the discovery of the structure of DNA.
The ENCODE paper chronicles all functioning parts in 1 per cent of the
human genome, based on input from 80 agencies, and researchers hope
next to complete the job.
http://www.thestar.com/printArticle/225245
Page 2 of 2
6/14/2007

Landmark study prompts rethink of genetic code
France 24 - world science news
WEDNESDAY, JUNE 13, 2007
By AFP
PARIS, June 13, 2007 (AFP) - The ground-breaking study, published in more than two dozen
papers in journals on both sides of the Atlantic, takes a small percentage of the genome to
pieces to draw up a "parts list," identifying the biological role of every component.
For the international team of investigators, the four-year project was the computer-equivalent of
passing a fine-toothed comb through a mountain of raw data.
Reporting in the British journal Nature and the US journal Genome Research on Thursday,
they suggest that an established theory about the genome should be consigned to history.
Under this view, the genome is rather like a ribbon studded with some 22,000 "nuggets" in the
form of genes, which make proteins, the essential stuff of life.
Genes -- deemed so valuable that some discoverers of them have been prompted to file
patents over them for commercial gain -- amount to only around a twentieth, or even less, of
the genetic code.
In between the genes and the sequences known to regulate their activity are long, tedious
stretches that appear to do nothing. The term for them is "junk" DNA, reflecting the
presumption that they are merely driftwood from our evolutionary past and have no biological
function.
But the work by the ENCODE (ENCyclopaedia of DNA Elements) consortium implies that this
nuggets-and-dross concept of DNA should be, well, junked.
The genome turns out to a highly complex, interwoven machine with very few inactive
stretches, the researchers report.
Genes, it transpires, are just one of many types of DNA sequences that have a functional role.
And "junk" DNA turns out to have an essential role in regulating the protein-making business.
Previously written off as silent, it emerges as a singer with its own discreet voice, part of a vast,
interacting molecular choir.
"The majority of the genome is copied, or transcribed, into RNA, which is the active molecule in
our cells, relaying information from the archival DNA to the cellular machinery," said Tim
Hubbard of the Wellcome Trust Sanger Institute, a British research group that was part of the
team.
"This is a remarkable finding, since most prior research suggested only a fraction of the
genome was transcribed."
Francis Collins, director of the US National Human Genome Research Institute (NHGRI), which
coralled 35 scientific groups from around the world into the ENCODE project, said the scientific
community "will need to rethink some long-held views about what genes are and what they do."
http://www.france24.com/france24Public/en/news/science/20070613-biothec-gen...
Page 1 of 2
6/13/2007

Landmark study prompts rethink of genetic code
"(...) This could have significant implications for efforts to identify the DNA sequences involved
in many human diseases," he said.
Another rethink is in offing about how the genome has evolved, said Collins.
Until now, researchers had thought that the pressure to survive would relentlessly sculpt the
human genome, leaving it with a slim, efficient core of genes that are essential for biological
function.
But the ENCODE consortium were surprised to find that the genome appears to be stuffed with
functional elements that offer no identifiable benefits in terms of survival or reproduction.
The researchers speculate that there is a point behind this survival of the evolutionary cull.
Humans could share with other animals a large pool of functional elements -- a "warehouse"
stuffed with a variety of tools on which each species can draw, enabling it to adapt according to
its environmental niche.
The ENCODE endeavour flows from the Human Genome Project, which concluded in April
2003 with the publication of a polished draft of the human genetic code.
But having the draft is not the same as knowing what is in it or how it works.
And this is essential for unlocking knowledge about our evolutionary odyssey, just as it is
needed for engineering new treatments for inherited disease.
The collaborative study focussed on 44 strategically chosen targets which together account for
about one percent of the genome, or about 30 million of the three billion "rungs" in the DNA
double-helix ladder.
The data is being placed in the public domain to help medical and other research.
Copyright © 2007 FRANCE 24. All rights reserved.
http://www.france24.com/france24Public/en/news/science/20070613-biothec-gen...
Page 2 of 2
6/13/2007

Svolta nello studio del Dna decifrato il "manuale di istruzioni" - Scienza & Tecno...
Ultimo aggiornamento giovedi 14.06.2007 ore 15.28
TECNOLOGIA & SCIENZA
Dopo la mappatura, il passo più importante: come funziona il codice della vita
E adesso si aprono nuove prospettive per le terapie mediche del futuro
Svolta nello studio del Dna
decifrato il "manuale di istruzioni"
di ALESSIA MANFREDI
Page 1 of 3
ROMA - Dopo la mappatura del codice della vita, arrivano ora i primi chiarimenti sul
funzionamento dei nostri geni. Il passo successivo alla lettura di quei tre miliardi di lettere che
compongono il Dna, tanto atteso, è finalmente arrivato: un "manuale di istruzioni" che getta
luce sull'attività del genoma. I risultati dell'impresa, nata dalla collaborazione internazionale di
oltre 80 paesi e 35 équipe di ricerca, tutti parte del programma Encode (the Encyclopedia of
Dna Elements), sono stati pubblicati su Nature. E la prosecuzione naturale del Progetto
Genoma, a detta degli scienziati, apre la strada ad una rivoluzione che promette importanti
ricadute anche per lo sviluppo di nuove terapie mediche.
Oltre 200 analisi per descrivere il comportamento del nostro codice genetico, o meglio, di una
http://www.repubblica.it/2006/08/sezioni/scienza_e_tecnologia/genetica/enciclope...
6/14/2007

Svolta nello studio del Dna decifrato il "manuale di istruzioni" - Scienza & Tecno...
sua piccola porzione, per ora: 30 milioni di basi nucleotidiche, pari all'1 per cento.
Page 2 of 3
Se qualche anno fa si è ottenuta la mappa dei geni, il significato del codice rimaneva per molti
aspetti oscuro. Si sapeva che racchiude tutte le istruzioni per sintetizzare tutte le molecole che
formano le cellule del nostro corpo, ma il modo in cui operava rimaneva un mistero. Ora, con il
progetto Encode, molti elementi del puzzle assumono un ruolo più preciso. I ricercatori sono
riusciti a capire come e dove si svolgono determinate funzioni biologiche, mettendo in
discussione certi dogmi e rivalutando quello che finora è stato chiamato "Dna spazzatura",
considerato cioè silente o inutile.
Per il genetista Bruno Dalla Piccola "l'annuncio rappresenta un progresso molto significativo".
"Se la mappatura del genoma era una fase preliminare, quella di assoluto rilievo è la
comprensione di come funzionano i geni", spiega a Repubblica.it.
"Se è vero che molte malattie sono causate da un loro funzionamento anomalo, capire come
agiscono gli interruttori che accendono e spengono queste anomalie significa avvicinarsi ad un
sogno: trovare i sistemi che regolano questi meccanismi ed intervenire a livello di terapia, con
effetti potenzialmente rivoluzionari. Certo non domani, ma è questa la prospettiva che si apre",
dice ancora il genetista.
Rivalutando certe sezioni del Dna finora tenute in secondo piano rispetto ai geni, questo studio
rivela aspetti inediti e offre qualche sorpresa. "L'immagine tradizionale del nostro genoma
come un insieme ben ordinato di geni indipendenti viene rimessa in discussione", annuncia il
consorzio internazionale di ricerca. Frutto di quattro anni di ricerche, questi risultati
"promettono di trasformare la nostra comprensione del funzionamento del genoma"
annunciano ancora gli scienziati, rivelando una rete complessa in cui i geni, gli elementi che
regolano la loro attività e altri tipi di sequenze di Dna interagiscono.
Tra le novità, i ricercatori hanno compreso che il Dna non codificante - quello cioè che non
serve a costruire le proteine all'interno della cellula, i mattoni elementari dell'organismo - e che
è la maggior parte, è trascritto in molecole di Rna (acido ribonucleico) che svolgono una
funzione fondamentale per la regolazione dell'attività del Dna stesso. Altro che spazzatura,
insomma: "I nuovi dati indicano che il genoma contiene pochissime sequenze inutilizzate ed i
geni sono solo uno dei numerosi tipi di sequenze di Dna che hanno un impatto fondamentale"
chiarisce in un comunicato il consorzio e il Laboratorio Europeo di Biologia Molecolare e di
Bioinformatica (EMBL-EBI) che ha guidato lo studio, insieme al National Human Genome
Research Institute (NHGRI), parte del NIH statunitense.
In alcune di queste sequenze "silenziose" del genoma sono state scoperte strutture di
cromatina (insiemi di geni e proteine che formano i cromosomi) sostanzialmente analoghe a
quelle che si trovano in regioni attive del Dna, che producono proteine. La presenza di aree
simili nel Dna di altri mammiferi suggerisce, infine, così "la possibilità che esista un grande
insieme di elementi neutrali biochimicamente attivi ma che non forniscono nessun beneficio
specifico all'organismo". E la conclusione degli scienziati è che "questo insieme potrebbe
servire come 'magazzino' della selezione naturale".
http://www.repubblica.it/2006/08/sezioni/scienza_e_tecnologia/genetica/enciclope...
6/14/2007

Svolta nello studio del Dna decifrato il "manuale di istruzioni" - Scienza & Tecno...
(13 giugno 2007)
Divisione La Repubblica
Gruppo Editoriale L’Espresso Spa - P.Iva 00906801006
http://www.repubblica.it/2006/08/sezioni/scienza_e_tecnologia/genetica/enciclope...
Page 3 of 3
6/14/2007

Un nuevo 'manual de instrucciones' del genoma reinterpreta el ADN humano | e...
Portada > Salud > Biociencia
ESTUDIO EN 'NATURE'
Un nuevo 'manual de instrucciones' del
genoma reinterpreta el ADN humano
'Nature' publica el proyecto ENCODE, que analiza todos los elementos del genoma
Además de los genes, numerosos elementos tienen un papel esencial en el ADN
Actualizado jueves 14/06/2007 20:49 (CET)
CARLOS MARTÍNEZ
MADRID.- Tres de los grandes retos científicos y
tecnológicos que se abordan estos días implican
el desarrollo de nuevos sistemas capaces de
definir, analizar y comparar gigantescas bases
de datos. Así ocurre con internet, con el
esfuerzo multidisciplinar en torno al cambio
climático y con la interpretación del genoma.
En este último campo, un consorcio
internacional ha desarrollado un nuevo sistema
para caracterizar con precisión la abundante y
heterogénea información que esconde el ADN
humano, incluida una gran parte de la secuencia considerada hasta ahora secundaria o
incluso inservible.
La fase piloto de la iniciativa, la identificación y análisis de los elementos con una función
biológica en el 1% del ADN humano, se publica en la última edición de 'Nature' y en otros 28
trabajos que difunde de forma simultánea la revista 'Genome Research'. El estudio es un primer
paso hacia la elaboración de una gramática completa del genoma.
A pesar de ser un trabajo exhaustivo, fruto de cuatro años de investigación de 35 grupos, los
estudios publicados representan sólo la primera etapa de la Enciclopedia de Elementos del DNA
(ENCODE, en sus siglas en inglés), el nombre de la iniciativa. En la empresa, desarrollada por
un consorcio internacional encabezado por los Institutos Nacionales de la Salud de EEUU,
participan la Universidad Pompeu Fabra, el Centro para la Regulación Genómica y el
Departamento de Genética de la Universidad de Barcelona, los tres en Cataluña, y el Centro
Nacional de Investigaciones Oncológicas, en Madrid.
No todo son genes
Representación de la secuencia de ADN. (Foto:
NCI)
Page 1 of 3
La investigación, diseñada como una prueba para evaluar si es posible la realización a gran
escala de la iniciativa, cambia la concepción tradicional del ADN humano como una "colección
ordenada de genes" por su descripción como una compleja red formada por diversos
elementos que interactúan entre sí. Los científicos han trazado las líneas generales de este
vasto mapa y descrito los principales elementos que lo componen, incluidos aquellos sobre los
http://elmundosalud.elmundo.es/elmundosalud/2007/06/13/biociencia/118175514...
6/15/2007

Un nuevo 'manual de instrucciones' del genoma reinterpreta el ADN humano | e...
que se sabía menos y que, al contrario de lo que se pensaba, tienen un papel esencial. Pero se
ignoran en gran medida los detalles.
Las múltiples relaciones entre los distintos elementos que componen el ADN y el patrón de
comportamiento de las redes que conforman el genoma no se comprenden. El llamado "libro de
la vida" sigue siendo "un elegante pero críptico depósito de información" -reza 'Nature'- sobre el
que todavía se sabe muy poco. El proyecto ENCODE abre nuevas vías para interpretarlo.
"Cuanto más sabemos del genoma humano, más apreciamos lo complicado que es trasladar la
información genómica a la función celular", explica Chris Gunter, uno de los editores de 'Nature'.
Es decir, no se sabe la clave del asunto: por qué el genoma humano culmina en la formación del
organismo. Gunter confía en que se logre una descripción del proceso a lo largo de los próximos
10 años.
Para lograrlo hay que superar numerosos obstáculos. Por ejemplo, la mayor parte de los análisis
se han centrado en los genes específicos que codifican proteínas y en los elementos que rodean
a este proceso. El esquema básico es el siguiente: cada gen tiene como función codificar al
menos una proteína; si se siguen linealmente los pasos, se entenderá la función de cada región
del ADN.
Sin embargo, así se abarca una mínima parte de la secuencia: únicamente entre el 1,5% y
el 2% del genoma responde a este ordenado modelo. La realidad es que el genoma es mucho
más que los genes que lo conforman. ¿Qué función cumple todo lo que se está dejando fuera del
análisis?
Nuevos descubrimientos
En la fase piloto del proyecto ENCODE se ha desarrollado un nuevo sistema que engloba todos
los elementos del ADN a los que se atribuye una función biológica: los genes (incluidos
tanto los que codifican proteínas como los que no cumplen esta función), los elementos que
controlan la transcripción de los genes y los que tienen como responsabilidad mantener la
estructura de los cromosomas y mediar en la dinámica de replicación del ADN.
A partir de este punto de vista global, el trabajo seleccionó 44 regiones. La selección representa
alrededor del 1% del genoma completo, es decir, unas 30 millones de pares de bases
nucleótidas, el elemento mínimo que compone la secuencia.
Algunos de los primeros hallazgos incluyen importantes descubrimientos sobre el papel de las
regiones de ADN que no participan en la codificación de proteínas. ENCODE supera la vieja
hipótesis que consideraba inactiva una gran parte del genoma, bautizado entonces como
"genoma basura".
Los nuevos datos muestran que sólo una mínima parte de la secuencia no cumple una función
biológica. El porcentaje del genoma desdeñado hasta ahora tiene en realidad "papeles
reguladores esenciales", escribe en 'Nature' John M. Greally, de la Facultad de Medicina Albert
Einstein (EEUU).
"Por ejemplo, en los intentos por encontrar las causas de enfermedades hereditarias los
investigadores estudian cientos de variaciones en la secuencia del genoma, conocidas como
poliformismos de un único nucleótido, para ver cuáles no se asocian de forma aleatoria con el
trastorno", explica Greally.
http://elmundosalud.elmundo.es/elmundosalud/2007/06/13/biociencia/118175514...
Page 2 of 3
6/15/2007

Un nuevo 'manual de instrucciones' del genoma reinterpreta el ADN humano | e...
"Recientemente, estos estudios mostraron varias secuencias asociadas con la diabetes tipo 2 y
sus manifestaciones relacionadas, pero sólo una minoría de las variaciones se encontraba dentro
de los genes", añade el especialista. "La información clave estaba oculta en las regiones de ADN
desdeñadas hasta ahora. Ahora tenemos que pensar cómo pueden estar contribuyendo estas
modificaciones a los riesgos, incluso de forma pequeña o sutil", añade Chris Gunter.
Portada > Salud > Biociencia
Dirección original de este artículo:
http://elmundosalud.elmundo.es/elmundosalud/2007/06/13/biociencia/1181755141.html
Page 3 of 3
© Mundinteractivos, S.A.
http://elmundosalud.elmundo.es/elmundosalud/2007/06/13/biociencia/118175514...
6/15/2007

06/14/2007
Media Contact: EDUARDO GERAQUE
Media Outlet: Folha de São Paulo
View Attachment: http://news.vocus.com/click/here.pl?z975484269&...
A biologia acaba de ficar mais
complicada. Os genes -trechos
de DNA que contém a 'receita'
para produzir proteínas que
compõem as células- podem
não ser tão decisivos assim para
a estrutura biológica das pessoas, revela um novo estudo. As
partes do DNA não atreladas
aos genes em si - já apelidadas
de 'DNA-lixo'- são também
vitais para a variabilidade das
linhagens de célula, afirma o
trabalho na revista 'Nature'.
A descoberta é anunciada por
um consórcio internacional, o
Encode (Enciclopédia dos Elementos do DNA, na sigla em inglês), que analisou apenas 1%
de todo o genoma humano, mas
em 11 tecidos diferentes. O resultado, pelo visto, vai de encontro a um consenso.
'É impossível não dizer que
esses resultados apontam para
um lugar onde nós também
chegamos', disse Sergio Verjovski-Almeida, da Universidade de São Paulo, à Folha. O estudo do
grupo brasileiro, publicado em março, também exaltou a importância dos trechos
não codificantes do DNA humano, ou seja, aqueles pedaços
de DNA que um dia foram chamados de lixo.
Os brasileiros analisaram
15% do genoma para apenas 3
tecidos. No caso do trabalho do
consórcio Encode, eles optaram por mais tecidos, porque
tudo indica que é essa variabilidade de linhagens celulares que
realmente importa. 'Eles mostraram que 93% das bases [não
só as dos genes] estudadas por
eles foram de alguma forma
transcritas para um tecido'.
Do ponto de vista conceitual,
explica Almeida, a genômica
agora está caminhando para
um diferenciação clara entre
função bioquímica e papel biológico. Ou seja, não basta
associar um determinado segmento
do DNA a uma proteína. É preciso questionar, afinal, qual o
papel que esse processo tem no
organismo?
É aí que entra em cena, no
mesmo patamar de importância que os próprios genes, as regiões do DNA que
estão entre
esses genes. 'Sem dúvida, agora
sabemos que tudo é muito mais
complexo. Esse papel biológico
está lá e tem um peso importante', disse ontem em entrevista coletiva o pesquisador
Francis Collins, diretor do Instituto de Pesquisa do Genoma
Humano dos Estados Unidos,
integrante do Encode.
Outra descoberta do grupo
internacional com a pesquisa
de apenas 1% do genoma humano - eles acham que tudo
encontrado até aqui estará presente também nos demais
99%- é importante para se entender mais sobre o processo
de evolução do homem.
A tese mais corrente entre os
cientistas é que os trechos do

DNA responsáveis pela transcrição da informação
genética
em proteínas seriam relativamente constantes ao longo do
tempo. Mas não foi isso que
apareceu agora.
Os pesquisadores do grupo,
definiram esse dado encontrado por eles, com o mais surpreendente de todos. Apenas
12% dos trechos responsáveis
pelas transcrições guardam algum tipo de conservação.
Texto Anterior: Próximo Texto:

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Grammatik der Gene viel komplexer als
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13.06.2007
Die Darstellung des
Biotechnologie-Unternehmens
Quiagen zeigt eine Doppelhelix
Home > Nachrichten > Vermischtes
London (dpa) Nach dieser Arbeit
müssen viele Biologiebücher neu
geschrieben werden: Im Erbmaterial
des Menschen sind viel mehr
Informationen gespeichert, als bislang
angenommen. Zudem ist die Grammatik
beim Ablesen der Gene viel
komplizierter als es den
wissenschaftlichen Vorstellungen
bislang entsprach.
des menschlichen DNA-Codes. Das berichtet das Konsortium ENCODE
aus 35 Forscherteams im Fachjournal
«Nature» (Bd. 447, S. 799) und in 28 Artikeln des Journals «Genome
Research» (Juniausgabe).
Die Reihenfolge der Erbgut-Bausteine wurde zwar schon im Jahr 2003
abschließend bestimmt, nun haben die Forscher aber bei einem Prozent
des Erbmaterials systematisch untersucht, was diese Bausteine tun.
Noch vor kurzem nahmen viele Wissenschaftler an, dass ein Großteil
des Erbmaterials aus funktionslosem «Müll» (Junk-DNA) besteht, der
zwischen den Genen liegt. Das ENCODE-Konsortium fand nun jedoch
heraus, dass die «Mehrzahl» der DNA-Bausteine tatsächlich abgelesen
wird. Die Funktion vieler dieser Abschriften kennen die Forscher
allerdings noch nicht. Die neuen Daten zeigen, dass das Genom nur
«sehr wenig» ungenutzte Sequenzen enthält, schreibt das beteiligte
Europäische Bioinformatik-Institut (EMBL-EBI) im britischen Hinxton. Es
hat die Daten der Forscherteams aus 80 Organisationen
zusammengefasst.
Nach den Erkenntnissen des ENCODE-Konsortiums gilt nicht mehr die
Vorschrift: Ein Gen ergibt ein Produkt. Denn ein Erbgut-Abschnitt kann
demnach zu verschiedenen Abschriften führen mit jeweils
unterschiedlichen Funktionen. «Es ist alles sehr viel komplizierter, als
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Impressum
man sich das vor ein bis zwei Jahren vorgestellt hat», sagte der
beteiligte Bioinformatiker Prof. Peter Stadler vom Fraunhofer- Institut
für Zelltherapie und Immunologie in Leipzig.
Das ENCODE-Konsortium hat viele zuvor unbekannte Startschalter zum
Genablesen identifiziert und zudem neue Sequenzen, die die Aktivität
der Gene regulieren. Außerdem fand es oft Genschalter hinter den
Genen und nicht wie bislang gedacht nur davor.
«Wir kennen jetzt im Wesentlichen die Mitspieler der Genregulation»,
sagte Stadler. «Der nächste Schritt wird sein, weitere Spielregeln
herauszukriegen.» Das habe große Auswirkungen für die Diagnostik und
Therapie von Krankheiten. «Es gibt die Hoffnung, künftig
Fehlregulationen von Genen besser zu erkennen.» Man könne die Arbeit
von ENCODE jedoch nicht isoliert betrachten, da das Wissen anderer
Forscher auch eine große Rolle bei den Erkenntnissen spiele.
Besondere Bedeutung hat die ENCODE-Arbeit auch für die
Evolutionsforschung: «Eine der größten Überraschungen war, dass wir
viele Kontrollelemente nicht mit anderen Arten teilen», sagte Manolis
Dermitzakis vom Wellcome Trust Sanger Institute. Das Erbgut sei
innerhalb der Evolution daher viel weniger stabil als bislang gedacht.
Zudem haben die Forscher entdeckt, dass auch das
Verpackungsmaterial der DNA, die Histone, eine wichtige Rolle beim
Ablesen des Erbguts und vor allem bei der Zellteilung spielt.
Die Wissenschaftsgemeinde müsse nun einige grundsätzliche
Betrachtungsweisen über Gene, ihre Funktion und die Evolution des
Erbguts überdenken, sagte der US-Genpionier Francis Collins, Direktor
des National Human Genome Research Institute (NHGRI). Er hatte die
Arbeit zur Entzifferung des Menschengenoms geleitet und hat jetzt eine
führende Rolle bei ENCODE. Die Abkürzung steht für ENCyclopedia Of
DNA Elements.
Das Konsortium ist ein Nachfolger des Humangenomprojekts, das das
menschliche Erbgut entziffert hat. Die Forscher haben in dem
Pilotprojekt zu ENCODE nun insgesamt ein Prozent des Erbguts aus 44
DNA-Regionen ausgewählt, die repräsentativ seien. Die Einzeldaten
sollen demnächst öffentlich zugänglich werden.
Betrachtet man das Erbgut des Menschen als ein Buch mit drei
Milliarden Bausteinen, so haben die Forscher nun neue Abschriften
davon gefunden und können mit ihren Arbeiten die Grammatik und
Zeichensetzung des Textes besser verstehen. Von einem Verständnis
des Gesamtwerkes sind sie jedoch noch weit entfernt.
Internet: www.genome.gov/ENCODE
Leserbrief | Artikel empfehlen | Druckansicht
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6/15/2007

CORDIS : News
News
New research challenges understanding of human genome
[Date: 2007-06-14]
Page 1 of 2
Results from a huge international effort to identify the functional components of the human genome are
challenging established views about how the genome works. Among other things, the concept of 'junk' DNA looks
set to be binned, as the findings reveal that most of the genome has a function of some kind.
The research, which was funded by a range of bodies including the EU, is published by the journal Nature, with 28
companion papers appearing in the journal Genome Research.
The work was carried out within the framework of the ENCODE (Encyclopedia of DNA Elements) project, which has
spent the past four years identifying and cataloguing the functional elements of 1% of the human genome.
The human genome was sequenced in April 2003. Together, the three billion base pairs ('letters') of the genome
contain all the information needed to turn a fertilised egg cell into an adult human being. While we have some
understanding of the parts of the genome that code for proteins, the function of the rest of the genome remains a
mystery.
'The problem is it is written in a language we are still trying to learn to understand,' said Francis Collins, Director
of the US' National Human Genome Research Institute (NHGRI).
The goal of the ENCODE project is to investigate the genome to find out what it is doing and why. In this initial
pilot phase, 30,000 base pairs, equivalent to 1% of the total genome, were targeted. Half of these were in regions
of the genome which are relatively well characterised, and the other half were picked at random.
Scientists from 80 organisations in 11 countries and representing a range of disciplines ran a battery of tests on
the target DNA sequences, sharing information, technology and data along the way. The result was over 200
datasets and over 600 million data points.
'This was a prime example of team science at its best,' commented Dr Collins. 'None of this data would have been
as rich without this sharing.'
'Our results reveal important principles about the organisation of functional elements in the human genome,
providing new perspectives on everything from DNA transcription to mammalian evolution,' said Ewan Birney of
the European Molecular Biology Laboratory, who led the data analysis work. 'In particular, we gained significant
insight into DNA sequences that do not encode proteins, which we knew very little about before.'
One of the most exciting findings was the fact that most of the DNA in our cells is active in some way, challenging
the idea that the genome consists of active protein-coding genes surrounded by vast amounts of inactive, socalled
'junk' DNA. Furthermore, many of these non-protein coding sequences overlap with protein-coding
sequences.
http://cordis.europa.eu/fetch?CALLER=EN_NEWS&ACTION=D&SESSION=&RC...
6/14/2007

CORDIS : News
'The junk is not junk. It is active. It does a lot of different things,' said Dr Birney.
Many of the regions which were once thought to be junk have turned out to be regulatory sequences, which tell
genes when and where they should be active. This finding will have implications for medicine, as many genetic
mutations associated with diseases are found in regulatory regions.
Another surprise for the scientists was the identification of 'neutral' sequences, which are being actively copied but
provide neither a benefit nor a problem to the organism. These neutral sequences have not been conserved during
evolution. The researchers speculate that these could be a source for new genetic variation in the future.
'It's like clutter in the attic,' explained Dr Collins. 'You wouldn't throw it away because you might need it.'
One of the goals of the project was to develop the tools to carry out the analysis and ensure the feasibility of the
project concept, which involved developing standards so that data from different laboratories and different
experimental processes could be compared properly.
'We are now in a position to scale this up!' said Dr Collins. 'We are prepared to go from 1% to the whole thing.'
'The goal for the next five years is delivering a more complete understanding across our genome,' added Dr
Birney. 'The ENCODE pilot project is the first step towards this goal.'
ENCODE:
http://www.genome.gov/encode/
Nature:
http://www.nature.com/nature/focus/encode/index.html
Genome Research:
http://www.genome.org/
All the articles are open access
Category: Projects
Data Source Provider: ENCODE project consortium, Nature
Document Reference: The ENCODE Project Consortium (2007) Identification and analysis of functional elements
in 1% of the human genome by the ENCODE pilot project. Nature 447: 799-816.
Programme or Service Acronym: MS-SE C, MS-A C, MS-D C, MS-E C, MS-UK C, FP6-INTEGRATING, FP6-
LIFESCIHEALTH, FRAMEWORK 6C
Subject Index: Biotechnology; Coordination, Cooperation; Medicine, Health; Scientific Research
RCN: 27851
http://cordis.europa.eu/fetch?CALLER=EN_NEWS&ACTION=D&SESSION=&RC...
Page 2 of 2
6/14/2007

Xinhua - English
欢迎访问新华网 - WWW.XINHUANET.COM >>
undefined
BEIJING, June 14 (Xinhuanet) -- An in-depth examination by 35 teams
of researchers from 80 different organizations in 11 countries who shared
notes on 1 percent of the human genome has revealed there is no such
thing as "junk DNA" and that some of what was considered "uselesslooking"
stretches of DNA may rewrite the book on evolution and causes of
some diseases.
Their findings, the start of the Encyclopedia of DNA Elements or
ENCODE Project, were published in the journals Nature and Genome
Research.
"This is a landmark in our understanding of human biology," said Dr.
Francis Collins, head of the National Human Genome Research Institute,
which funded much of the work.
Some scientists were surprised that human beings had only about
30,000 genes after the human genome was published in 2003. Rice, for
instance, has 50,000. The new study confirms what many genetics experts
had suspected — the genes are important, but so is the other DNA, the
biological code for every living thing.
What they discovered is that even DNA outside the genes transcribes
information. Transcription is the process that turns DNA into something
useful — such as a protein.
Much of this action is going on outside the genes in the so-called
regulatory regions that affect how and when a gene activates, Collins
said. The researchers discovered 4,491 of these so-called transcription
start sites, "almost tenfold more than the number of established genes,"
they wrote in the Nature paper.
Ewan Birney of the European Molecular Biology Laboratory's European
Bioinformatics Institute in Cambridge said this helped explain how such a
complex creature as a human arose from just four letters of code repeated
over and over.
"The junk is not junk. It is really active," Birney told reporters.
This could be useful in understanding and treating disease.
(Agencies)
http://news.xinhuanet.com/english/2007-06/14/content_6242519.htm
Page 1 of 1
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6/14/2007