Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

A Corrigendum to this article was published on 12 March 2009


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.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Experimental validation of duplication map.
Figure 2: Shared versus lineage-specific duplications and great-ape polymorphism.
Figure 3: Convergent gene duplication expansion in African great apes but not humans.
Figure 4: Rates of segmental duplication.


  1. King, M. C. & Wilson, A. C. Evolution at two levels in humans and chimpanzees. Science 188, 107–116 (1975)

    ADS  CAS  Article  Google Scholar 

  2. Goodman, M. The role of immunochemical differences in the phyletic development of human behavior. Hum. Biol. 33, 131–162 (1961)

    CAS  PubMed  Google Scholar 

  3. Yunis, J. J. & Prakash, O. The origin of man: a chromosomal pictorial legacy. Science 215, 1525–1530 (1982)

    ADS  CAS  Article  Google Scholar 

  4. Wu, C. I. & Li, W. H. Evidence for higher rates of nucleotide substitution in rodents than in man. Proc. Natl Acad. Sci. USA 82, 1741–1745 (1985)

    ADS  CAS  Article  Google Scholar 

  5. Li, W. H. & Tanimura, M. The molecular clock runs more slowly in man than in apes and monkeys. Nature 326, 93–96 (1987)

    ADS  CAS  Article  Google Scholar 

  6. Elango, N., Thomas, J. W. & Yi, S. V. Variable molecular clocks in hominoids. Proc. Natl Acad. Sci. USA 103, 1370–1375 (2006)

    ADS  CAS  Article  Google Scholar 

  7. Steiper, M. E., Young, N. M. & Sukarna, T. Y. Genomic data support the hominoid slowdown and an Early Oligocene estimate for the hominoid-cercopithecoid divergence. Proc. Natl Acad. Sci. USA 101, 17021–17026 (2004)

    ADS  CAS  Article  Google Scholar 

  8. Mouse Genome Sequencing Consortium Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562 (2002)

    Article  Google Scholar 

  9. Rhesus Macaque Genome Sequencing and Analysis Consortium Evolutionary and biomedical insights from the rhesus macaque genome. Science 316, 222–234 (2007)

    Article  Google Scholar 

  10. The Chimpanzee Sequencing and Analysis Consortium Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69–87 (2005)

    Article  Google Scholar 

  11. Hahn, M. W., Demuth, J. P. & Han, S. G. Accelerated rate of gene gain and loss in primates. Genetics 177, 1941–1949 (2007)

    Article  Google Scholar 

  12. Dumas, L. et al. Gene copy number variation spanning 60 million years of human and primate evolution. Genome Res. 17, 1266–1277 (2007)

    CAS  Article  Google Scholar 

  13. Cheng, Z. et al. A genome-wide comparison of recent chimpanzee and human segmental duplications. Nature 437, 88–93 (2005)

    ADS  CAS  Article  Google Scholar 

  14. Jiang, Z., Hubley, R., Smit, A. & Eichler, E. E. DupMasker: A tool for annotating primate segmental duplications. Genome Res. 18, 1362–1368 (2008)

    CAS  Article  Google Scholar 

  15. Stankiewicz, P., Shaw, C. J., Withers, M., Inoue, K. & Lupski, J. R. Serial segmental duplications during primate evolution result in complex human genome architecture. Genome Res. 14, 2209–2220 (2004)

    CAS  Article  Google Scholar 

  16. Perry, G. H. et al. Hotspots for copy number variation in chimpanzees and humans. Proc. Natl Acad. Sci. USA 103, 8006–8011 (2006)

    ADS  CAS  Article  Google Scholar 

  17. Lee, A. S. et al. Analysis of copy number variation in the rhesus macaque genome identifies candidate loci for evolutionary and human disease studies. Hum. Mol. Genet. 17, 1127–1136 (2008)

    CAS  Article  Google Scholar 

  18. Levy, S. et al. The diploid genome sequence of an individual human. PLoS Biol. 5, e254 (2007)

    Article  Google Scholar 

  19. Wheeler, D. A. et al. The complete genome of an individual by massively parallel DNA sequencing. Nature 452, 872–876 (2008)

    ADS  CAS  Article  Google Scholar 

  20. Tuzun, E. et al. Fine-scale structural variation of the human genome. Nature Genet. 37, 727–732 (2005)

    CAS  Article  Google Scholar 

  21. Newman, T. L. et al. A genome-wide survey of structural variation between human and chimpanzee. Genome Res. 15, 1344–1356 (2005)

    CAS  Article  Google Scholar 

  22. Jiang, Z. et al. Ancestral reconstruction of segmental duplications reveals punctuated cores of human genome evolution. Nature Genet. 39, 1361–1368 (2007)

    CAS  Article  Google Scholar 

  23. Lee, J. A. & Lupski, J. R. Genomic rearrangements and gene copy-number alterations as a cause of nervous system disorders. Neuron 52, 103–121 (2006)

    CAS  Article  Google Scholar 

  24. Sharp, A. J. et al. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome. Nature Genet. 38, 1038–1042 (2006)

    CAS  Article  Google Scholar 

  25. The International Schizophrenia Consortium Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455, 237–241 (2008)

    Article  Google Scholar 

  26. Sebat, J. et al. Strong association of de novo copy number mutations with autism. Science 316, 445–449 (2007)

    ADS  CAS  Article  Google Scholar 

  27. Aitman, T. J. et al. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature 439, 851–855 (2006)

    ADS  CAS  Article  Google Scholar 

  28. Hollox, E. J. et al. Psoriasis is associated with increased β-defensin genomic copy number. Nature Genet. 40, 23–25 (2008)

    CAS  Article  Google Scholar 

  29. Gonzalez, E. et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 307, 1434–1440 (2005)

    ADS  CAS  Article  Google Scholar 

  30. Bailey, J. A. et al. Recent segmental duplications in the human genome. Science 297, 1003–1007 (2002)

    ADS  CAS  Article  Google Scholar 

Download references


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.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Evan E. Eichler.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures S1-S7 with Legends (PDF 1056 kb)

Supplementary Tables

This file contains Supplementary Tables 1-11 (XLS 2210 kb)

Supplementary Information

This file contains Supplementary Notes and Data with Supplementary Note Tables 1-16 and Supplementary Note Figures 1-17 and Supplementary References (PDF 1983 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing