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

HOW GENOMES EVOlvE
227
Mutations in the DNA Sequences That Control Gene Expression
Have Driven Many of the Evolutionary Changes in Vertebrates
The vast hoard of genomic sequence data now being accumulated can be explored
in many other ways to reveal events that happened even hundreds of millions of
years ago. For example, one can attempt to trace the origins of the regulatory elements
in DNA that have played critical parts in vertebrate evolution. One such
study began with the identification of nearly 3 million noncoding sequences, averaging
28 base pairs in length, that have been conserved in recent vertebrate evolution
while being absent in more ancient ancestors. Each of these special non-coding
sequences is likely to represent a functional innovation peculiar to a particular
branch of the vertebrate family tree, and most of them are thought to consist of
regulatory DNA that governs the expression of a neighboring gene. Given full
genome sequences, one can identify the genes that lie closest and thus appear
most likely to have fallen under the sway of these novel regulatory elements. By
comparing many different species, with known divergence times, one can also
estimate when each such regulatory element came into existence as a conserved
feature. The findings suggest remarkable evolutionary differences between the
various functional classes of genes (Figure 4–74). Conserved regulatory elements
that originated early in vertebrate evolution—that is, more than about 300 million
years ago, which is when the mammalian lineage split from the lineage leading to
birds and reptiles—seem to be mostly associated with genes that code for transcription
regulator proteins and for proteins with roles in organizing embryonic
development. Then came an era when the regulatory DNA innovations arose next
to genes coding for receptors for extracellular signals. Finally, over the course of
the past 100 million years, the regulatory innovations seem to have been concentrated
in the neighborhood of genes coding for proteins (such as protein kinases)
that function to modify other proteins post-translationally.
Many questions remain to be answered about these phenomena and what
they mean. One possible interpretation is that the logic—the circuit diagram—of
the gene regulatory network in vertebrates was established early, and that more
recent evolutionary change has mainly occurred through the tuning of quantitative
parameters. This could help to explain why, among the mammals, for example,
the basic body plan—the topology of the tissues and organs—has been largely
conserved.
Gene Duplication Also Provides an Important Source of Genetic
Novelty During Evolution
Evolution depends on the creation of new genes, as well as on the modification
of those that already exist. How does this occur? When we compare organisms
that seem very different—a primate with a rodent, for example, or a mouse with
a fish—we rarely encounter genes in the one species that have no homolog in the
development and
transcription
regulation
reception of
extracellular signals
post-translational
protein
modification
500 400 300 200 100 0
millions of years before present
HUMAN
MOUSE
COW
PLATYPUS
CHICKEN
FROG
FISH
Figure 4–74 The types of changes
in gene regulation inferred to have
predominated during the evolution of
our vertebrate ancestors. To produce
the information summarized in this plot,
wherever possible the type of gene
regulated by each conserved noncoding
sequence was inferred from the identity of
its closest protein-coding gene. The fixation
time for each conserved sequence was
then used to derive the conclusions shown.
(Based on C.B. Lowe et al., Science
333:1019–1024, 2011. With permission
from AAAS.)