A burst of segmental duplications in the genome of the African great ape ancestor

Abstract

With four primate genome sequences now available — macaque, orang-utan, chimpanzee and human — it has become possible to construct a comparative segmental duplication map of four primate genomes. This has now been done, and the resulting map used to reconstruct the evolutionary history of all human segmental duplications. The ancestral branch leading to humans and the African great apes shows a fourfold acceleration of segmental duplication accumulation at a time when other mutational processes such as single-base-pair mutation were slowing. This apparent burst of activity may be the result of a change in the effective population size or generation time, or imply a period of genomic destabilization. A comparative segmental duplication map of four primate genomes that allows the evolutionary history of all human segmental duplications to be reconstructed is presented. It reveals a fourfold acceleration of segmental duplication accumulation during the speciation of human, chimpanzee and gorilla at a time when other mutational processes were slowing, and also provides a detailed evolutionary history of all human segmental duplications as a resource to the human genetics community. It is generally accepted that the extent of phenotypic change between human and great apes is dissonant with the rate of molecular change1. Between these two groups, proteins are virtually identical1,2, cytogenetically there are few rearrangements that distinguish ape–human chromosomes3, and rates of single-base-pair change4,5,6,7 and retrotransposon activity8,9,10 have slowed particularly within hominid lineages when compared to rodents or monkeys. Studies of gene family evolution indicate that gene loss and gain are enriched within the primate lineage11,12. Here, we perform a systematic analysis of duplication content of four primate genomes (macaque, orang-utan, chimpanzee and human) in an effort to understand the pattern and rates of genomic duplication during hominid evolution. We find that the ancestral branch leading to human and African great apes shows the most significant increase in duplication activity both in terms of base pairs and in terms of events. This duplication acceleration within the ancestral species is significant when compared to lineage-specific rate estimates even after accounting for copy-number polymorphism and homoplasy. We discover striking examples of recurrent and independent gene-containing duplications within the gorilla and chimpanzee that are absent in the human lineage. Our results suggest that the evolutionary properties of copy-number mutation differ significantly from other forms of genetic mutation and, in contrast to the hominid slowdown of single-base-pair mutations, there has been a genomic burst of duplication activity at this period during human evolution.