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.
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We thank H. Mefford, A. Itsara, G. Cooper, T. Brown and G. McVicker for comments during the preparation of this manuscript. The authors are also grateful to J. Sikela and L. Dumas for assistance with the comparison to cDNA microarray data sets. We are grateful to L. Faust, J. Rogers, Southwest National Primate Research Center (P51-RR013986) and P. Parham for providing some of the primate material used in this study and to M. Adams for providing the alignments for the positive selection analysis. We also thank the large genome sequencing centres for early access to the whole genome sequence data for targeted analysis of segmental duplications. This work was supported, in part, by an NIH grant HG002385 to E.E.E. and NIH grant U54 HG003079 to R.K.W. and E.R.M. INB is a platform of Genoma España. T.M.-B. is supported by a Marie Curie fellowship and by Departament d’Educació i Universitats de la Generalitat de Catalunya. E.E.E. is an investigator of the Howard Hughes Medical Institute.
Author Contributions E.E.E. planned the project. M.V. and M.F.C. performed the FISH experiments. T.A.G., L.W.H., L.A.F., E.R.M. and R.K.W. generated the orang-utan WGS sequences. T.M.-B., J.M.K., Z.C., Z.J., L.C., E.E.E. and S.G. analysed the data. C.B. performed the array-CGH experiments. T.M.-B., R.M.-B. and P.S. characterized the chromosome 10 expansion. C.A. and G.A. generated the Venter/Watson comparative duplication maps. A.N. developed the maximum likelihood evolutionary model. T.M.-B., J.M.K. and E.E.E. wrote the paper.
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Marques-Bonet, T., Kidd, J., Ventura, M. et al. A burst of segmental duplications in the genome of the African great ape ancestor. Nature 457, 877–881 (2009). https://doi.org/10.1038/nature07744
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