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.) 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.
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.