Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

224 Chapter 4: DNA, Chromosomes, and Genomes
0.0
Fugu gene
100.0
thousands of nucleotide pairs
that modern humans have inherited specific genes from them (Figure 4–72). The
average difference in DNA sequence between humans and Neanderthals shows
that our two lineages diverged somewhere between 270,000 and 440,000 years
ago, well before the time that humans are believed to have migrated out of Africa.
But what about deciphering
MBoC6
the
m4.82/4.70
genomes of much older ancestors, those for
which no useful DNA samples can be isolated? For organisms that are as closely
related as human and chimpanzee, we saw that this may not be difficult: reference
to the gorilla sequence can be used to sort out which of the few sequence differences
between human and chimpanzee are inherited from our common ancestor
some 6 million years ago (see Figure 4–64). And for an ancestor that has produced
a large number of different organisms alive today, the DNA sequences of many
species can be compared simultaneously to unscramble much of the ancestral
sequence, allowing scientists to derive DNA sequences much farther back in time.
For example, from the genome sequences currently being obtained for dozens of
modern placental mammals, it should be possible to infer much of the genome
sequence of their 100 million-year-old common ancestor—the precursor of species
as diverse as dog, mouse, rabbit, armadillo, and human (see Figure 4–66).
Multispecies Sequence Comparisons Identify Conserved DNA
Sequences of Unknown Function
The mass of DNA sequence now in databases (hundreds of billions of nucleotide
pairs) provides a rich resource that scientists can mine for many purposes. This
information can be used not only to unscramble the evolutionary pathways that
have led to modern organisms, but also to provide insights into how cells and
organisms function. Perhaps the most remarkable discovery in this realm comes
from the observation that a striking amount of DNA sequence that does not code
for protein has been conserved during mammalian evolution (see Table 4–1,
p. 184). This is most clearly revealed when we align and compare DNA synteny
180.0
human gene
Figure 4–71 Comparison of the
genomic sequences of the human
and Fugu genes encoding the protein
huntingtin. Both genes (indicated in red)
contain 67 short exons that align in 1:1
correspondence to one another; these
exons are connected by curved lines.
The human gene is 7.5 times larger than
the Fugu gene (180,000 versus 24,000
nucleotide pairs). The size difference is
entirely due to larger introns in the human
gene. The larger size of the human
introns is due in part to the presence of
retrotransposons (discussed in Chapter
5), whose positions are represented by
green vertical lines; the Fugu introns lack
retrotransposons. In humans, mutation of
the huntingtin gene causes Huntington’s
disease, an inherited neurodegenerative
disorder. (Adapted from S. Baxendale et
al., Nat. Genet. 10:67–76, 1995. With
permission from Macmillan Publishers Ltd.)
Figure 4–72 The Neanderthals. (A) Map
of Europe showing the location of the
cave in Croatia where most of the bones
used to isolate the DNA used to derive
the Neanderthal genome sequence were
discovered. (B) Photograph of the Vindija
cave. (C) Photograph of the 38,000-yearold
bones from Vindija. More recent
studies have succeeded in extracting
DNA sequence information from hominid
remains that are considerably older (see
Movie 8.3). (B, courtesy of Johannes
Krause; C, from R.E. Green et al., Science
328: 710–722, 2010. Reprinted with
permission from AAAS.)
cave in
Vindija, Croatia
(A) (B) (C)
5 cm