• 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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    & Evolution at two levels in humans and chimpanzees. Science 188, 107–116 (1975)

  2. 2.

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

  3. 3.

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

  4. 4.

    & Evidence for higher rates of nucleotide substitution in rodents than in man. Proc. Natl Acad. Sci. USA 82, 1741–1745 (1985)

  5. 5.

    & The molecular clock runs more slowly in man than in apes and monkeys. Nature 326, 93–96 (1987)

  6. 6.

    , & Variable molecular clocks in hominoids. Proc. Natl Acad. Sci. USA 103, 1370–1375 (2006)

  7. 7.

    , & 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)

  8. 8.

    Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562 (2002)

  9. 9.

    Evolutionary and biomedical insights from the rhesus macaque genome. Science 316, 222–234 (2007)

  10. 10.

    Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69–87 (2005)

  11. 11.

    , & Accelerated rate of gene gain and loss in primates. Genetics 177, 1941–1949 (2007)

  12. 12.

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

  13. 13.

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

  14. 14.

    , , & DupMasker: A tool for annotating primate segmental duplications. Genome Res. 18, 1362–1368 (2008)

  15. 15.

    , , , & Serial segmental duplications during primate evolution result in complex human genome architecture. Genome Res. 14, 2209–2220 (2004)

  16. 16.

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

  17. 17.

    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)

  18. 18.

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

  19. 19.

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

  20. 20.

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

  21. 21.

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

  22. 22.

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

  23. 23.

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

  24. 24.

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

  25. 25.

    Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455, 237–241 (2008)

  26. 26.

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

  27. 27.

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

  28. 28.

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

  29. 29.

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

  30. 30.

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

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


  1. Department of Genome Sciences, University of Washington and the Howard Hughes Medical Institute, Seattle, Washington 98195, USA

    • Tomas Marques-Bonet
    • , Jeffrey M. Kidd
    • , Ze Cheng
    • , Zhaoshi Jiang
    • , Carl Baker
    • , Ray Malfavon-Borja
    • , Can Alkan
    • , Gozde Aksay
    • , Santhosh Girirajan
    • , Priscillia Siswara
    • , Lin Chen
    •  & Evan E. Eichler
  2. Institut de Biologia Evolutiva (UPF-CSIC), 08003 Barcelona, Catalonia, Spain

    • Tomas Marques-Bonet
    •  & Arcadi Navarro
  3. Sezione di Genetica-Dipartimento di Anatomia Patologica e Genetica, University of Bari, 70125 Bari, Italy

    • Mario Ventura
    •  & Maria Francesca Cardone
  4. Genome Sequencing Center, Washington University School of Medicine, St Louis, Missouri 63108, USA

    • Tina A. Graves
    • , LaDeana W. Hillier
    • , Lucinda A. Fulton
    • , Elaine R. Mardis
    •  & Richard K. Wilson
  5. Institució Catalana de Recerca i Estudis Avançats (ICREA) and Instituto Nacional de Bioinformática (INB), Dr. Aiguader 88, 08003 Barcelona, Spain

    • Arcadi Navarro


  1. Search for Tomas Marques-Bonet in:

  2. Search for Jeffrey M. Kidd in:

  3. Search for Mario Ventura in:

  4. Search for Tina A. Graves in:

  5. Search for Ze Cheng in:

  6. Search for LaDeana W. Hillier in:

  7. Search for Zhaoshi Jiang in:

  8. Search for Carl Baker in:

  9. Search for Ray Malfavon-Borja in:

  10. Search for Lucinda A. Fulton in:

  11. Search for Can Alkan in:

  12. Search for Gozde Aksay in:

  13. Search for Santhosh Girirajan in:

  14. Search for Priscillia Siswara in:

  15. Search for Lin Chen in:

  16. Search for Maria Francesca Cardone in:

  17. Search for Arcadi Navarro in:

  18. Search for Elaine R. Mardis in:

  19. Search for Richard K. Wilson in:

  20. Search for Evan E. Eichler in:

Corresponding author

Correspondence to Evan E. Eichler.

Supplementary information

PDF files

  1. 1.

    Supplementary Figures

    This file contains Supplementary Figures S1-S7 with Legends

  2. 2.

    Supplementary Information

    This file contains Supplementary Notes and Data with Supplementary Note Tables 1-16 and Supplementary Note Figures 1-17 and Supplementary References

Excel files

  1. 1.

    Supplementary Tables

    This file contains Supplementary Tables 1-11

About this article

Publication history






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.