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

228 Chapter 4: DNA, Chromosomes, and Genomes
other. Genes without homologous counterparts are relatively scarce even when
we compare such divergent organisms as a mammal and a worm. On the other
hand, we frequently find gene families that have different numbers of members in
different species. To create such families, genes have been repeatedly duplicated,
and the copies have then diverged to take on new functions that often vary from
one species to another.
Gene duplication occurs at high rates in all evolutionary lineages, contributing
to the vigorous process of DNA addition discussed previously. In a detailed study
of spontaneous duplications in yeast, duplications of 50,000 to 250,000 nucleotide
pairs were commonly observed, most of which were tandemly repeated. These
appeared to result from DNA replication errors that led to the inexact repair of
double-strand chromosome breaks. A comparison of the human and chimpanzee
genomes reveals that, since the time that these two organisms diverged, such segmental
duplications have added about 5 million nucleotide pairs to each genome
every million years, with an average duplication size being about 50,000 nucleotide
pairs (although there are some duplications five times larger). In fact, if one
counts nucleotides, duplication events have created more differences between
our two species than have single-nucleotide substitutions.
Duplicated Genes Diverge
What is the fate of newly duplicated genes? In most cases, there is presumed to
be little or no selection—at least initially—to maintain the duplicated state since
either copy can provide an equivalent function. Hence, many duplication events
are likely to be followed by loss-of-function mutations in one or the other gene.
This cycle would functionally restore the one-gene state that preceded the duplication.
Indeed, there are many examples in contemporary genomes where one copy
of a duplicated gene can be seen to have become irreversibly inactivated by multiple
mutations. Over time, the sequence similarity between such a pseudogene
and the functional gene whose duplication produced it would be expected to be
eroded by the accumulation of many mutations in the pseudogene—the homologous
relationship eventually becoming undetectable.
An alternative fate for gene duplications is for both copies to remain functional,
while diverging in their sequence and pattern of expression, thus taking
on different roles. This process of “duplication and divergence” almost certainly
explains the presence of large families of genes with related functions in biologically
complex organisms, and it is thought to play a critical role in the evolution
of increased biological complexity. An examination of many different eukaryotic
genomes suggests that the probability that any particular gene will undergo a
duplication event that spreads to most or all individuals in a species is approximately
1 percent every million years.
Whole-genome duplications offer particularly dramatic examples of the duplication–divergence
cycle. A whole-genome duplication can occur quite simply: all
that is required is one round of genome replication in a germ-line cell lineage
without a corresponding cell division. Initially, the chromosome number simply
doubles. Such abrupt increases in the ploidy of an organism are common, particularly
in fungi and plants. After a whole-genome duplication, all genes exist
as duplicate copies. However, unless the duplication event occurred so recently
that there has been little time for subsequent alterations in genome structure,
the results of a series of segmental duplications—occurring at different times—
are hard to distinguish from the end product of a whole-genome duplication. In
mammals, for example, the role of whole-genome duplications versus a series of
piecemeal duplications of DNA segments is quite uncertain. Nevertheless, it is
clear that a great deal of gene duplication has occurred in the distant past.
Analysis of the genome of the zebrafish, in which at least one whole-genome
duplication is thought to have occurred hundreds of millions of years ago, has cast
some light on the process of gene duplication and divergence. Although many
duplicates of zebrafish genes appear to have been lost by mutation, a significant
fraction—perhaps as many as 30–50%—have diverged functionally while both