Skip to main content

Thank you for visiting nature.com. 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 genome-wide comparison of recent chimpanzee and human segmental duplications

Abstract

We present a global comparison of differences in content of segmental duplication between human and chimpanzee, and determine that 33% of human duplications (> 94% sequence identity) are not duplicated in chimpanzee, including some human disease-causing duplications. Combining experimental and computational approaches, we estimate a genomic duplication rate of 4–5 megabases per million years since divergence. These changes have resulted in gene expression differences between the species. In terms of numbers of base pairs affected, we determine that de novo duplication has contributed most significantly to differences between the species, followed by deletion of ancestral duplications. Post-speciation gene conversion accounts for less than 10% of recent segmental duplication. Chimpanzee-specific hyperexpansion (> 100 copies) of particular segments of DNA have resulted in marked quantitative differences and alterations in the genome landscape between chimpanzee and human. Almost all of the most extreme differences relate to changes in chromosome structure, including the emergence of African great ape subterminal heterochromatin. Nevertheless, base per base, large segmental duplication events have had a greater impact (2.7%) in altering the genomic landscape of these two species than single-base-pair substitution (1.2%).

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Chimpanzee segmental duplication detection on human genome assembly NCBI-34 (build 34).
Figure 2: Sequence identity spectra of human only versus shared duplications.
Figure 3: Sequence structure of chimpanzee subterminal duplication.
Figure 4: A chimpanzee hyperexpansion of a shared segmental duplication.

References

  1. Bailey, J. A., Baertsch, R., Kent, W. J., Haussler, D. & Eichler, E. E. Hotspots of mammalian chromosomal evolution. Genome Biol. 5, R23 (2004)

    Article  PubMed  PubMed Central  Google Scholar 

  2. She, X. et al. The structure and evolution of centromeric transition regions within the human genome. Nature 430, 857–864 (2004)

    Article  CAS  ADS  PubMed  Google Scholar 

  3. Armengol, L., Pujana, M. A., Cheung, J., Scherer, S. W. & Estivill, X. Enrichment of segmental duplications in regions of breaks of synteny between the human and mouse genomes suggest their involvement in evolutionary rearrangements. Hum. Mol. Genet. 12, 2201–2208 (2003)

    Article  CAS  PubMed  Google Scholar 

  4. Trask, B. et al. Members of the olfactory receptor gene family are contained in large blocks of DNA duplicated polymorphically near the ends of human chromosomes. Hum. Mol. Genet. 7, 13–26 (1998)

    Article  CAS  PubMed  Google Scholar 

  5. Eichler, E. E. et al. Duplication of a gene-rich cluster between 16p11.1 and Xq28: a novel pericentromeric-directed mechanism for paralogous genome evolution. Hum. Mol. Genet. 5, 899–912 (1996)

    Article  CAS  PubMed  Google Scholar 

  6. Ventura, M. et al. Neocentromeres in 15q24–26 map to duplicons which flanked an ancestral centromere in 15q25. Genome Res. 13, 2059–2068 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Johnson, M. E. et al. Positive selection of a gene family during the emergence of humans and African apes. Nature 413, 514–519 (2001)

    Article  CAS  ADS  PubMed  Google Scholar 

  8. Courseaux, A. & Nahon, J. L. Birth of two chimeric genes in the Hominidae lineage. Science 291, 1293–1297 (2001)

    Article  CAS  ADS  PubMed  Google Scholar 

  9. Stefansson, H. et al. A common inversion under selection in Europeans. Nature Genet. 37, 129–137 (2005)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  ADS  PubMed  Google Scholar 

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

    Article  CAS  ADS  PubMed  Google Scholar 

  12. Khaitovich, P. et al. Regional patterns of gene expression in human and chimpanzee brains. Genome Res. 14, 1462–1473 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sebat, J. et al. Large-scale copy number polymorphism in the human genome. Science 305, 525–528 (2004)

    Article  CAS  ADS  PubMed  Google Scholar 

  14. Iafrate, A. J. et al. Detection of large-scale variation in the human genome. Nature Genet. 36, 949–951 (2004)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  16. Sharp, A. J. et al. Segmental duplications and copy number variation in the human genome. Am. J. Hum. Genet. 77, 78–88 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fredman, D. et al. Complex SNP-related sequence variation in segmental genome duplications. Nature Genet. 36, 861–866 (2004)

    Article  CAS  PubMed  Google Scholar 

  18. Stankiewicz, P. & Lupski, J. R. Genomic architecture, rearrangements and genomic disorders. Trends Genet. 18, 74–82 (2002)

    Article  CAS  PubMed  Google Scholar 

  19. Zhang, L., Lu, H. H., Chung, W. Y., Yang, J. & Li, W. H. Patterns of segmental duplication in the human genome. Mol. Biol. Evol. 22, 135–141 (2005)

    Article  CAS  PubMed  Google Scholar 

  20. Bailey, J. A., Yavor, A. M., Massa, H. F., Trask, B. J. & Eichler, E. E. Segmental duplications: organization and impact within the current human genome project assembly. Genome Res. 11, 1005–1017 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. The Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature doi:10.1038/nature04072 (this issue)

  22. Tuzun, E., Bailey, J. A. & Eichler, E. E. Recent segmental duplications in the working draft assembly of the brown Norway rat. Genome Res. 14, 493–506 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bailey, J. A., Church, D. M., Ventura, M., Rocchi, M. & Eichler, E. E. Analysis of segmental duplications and genome assembly in the mouse. Genome Res. 14, 789–801 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. International Human Genome Sequencing Consortium, Finishing the euchromatic sequence of the human genome. Nature 431, 931–945 (2004)

    Article  ADS  Google Scholar 

  25. Rozen, S. et al. Abundant gene conversion between arms of massive palindromes in human and ape Y chromosomes. Nature 423, 873–876 (2003)

    Article  CAS  ADS  PubMed  Google Scholar 

  26. Chen, F. C. & Li, W. H. Genomic divergences between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees. Am. J. Hum. Genet. 68, 444–456 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Royle, N. J., Baird, D. M. & Jeffreys, A. J. A subterminal satellite located adjacent to telomeres in chimpanzees is absent from the human genome. Nature Genet. 6, 52–56 (1994)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  ADS  PubMed  Google Scholar 

  29. Fan, Y., Linardopoulou, E., Friedman, C., Williams, E. & Trask, B. J. Genomic structure and evolution of the ancestral chromosome fusion site in 2q13–2q14.1 and paralogous regions on other human chromosomes. Genome Res. 12, 1651–1662 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fortna, A. et al. Lineage-specific gene duplication and loss in human and great ape evolution. PLoS Biol. 2, E207 (2004)

    Article  PubMed  PubMed Central  Google Scholar 

  31. Khaitovich, P. et al. Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees. Science (in the press)

Download references

Acknowledgements

We thank M. Lachmann, I. Hellman and G. Vessere for technical assistance; the Chimpanzee Sequencing and Analysis Consortium for access to the chimpanzee sequence data before publication; A. Force for discussions; and J. Pecotte, S. Warren and J. Rogers for providing some of the primate material used in this study. This work was supported by grants from the National Human Genome Research Institute, the National Institute of General Medical Sciences, Centro di Eccellenza Geni in campo Biosanitario e Agroalimentare, Ministero Italiano della Università e della Ricerca, the European Commission and the Bundesministerium für Bildung und Forschung.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Evan E. Eichler.

Ethics declarations

Competing interests

Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Supplementary information

Supplementary Methods

Additional description of the methods used in this study. (DOC 60 kb)

Supplementary Figure Legends

Text to accompany the below Supplementary Figures. (DOC 41 kb)

Supplementary Figures

This file contains Supplementary Figures S1-S6, S8. (PPT 7715 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 1. (See chimpparalogy.gs.washington.edu) (PDF 14982 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 2. (PDF 15010 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 3. (PDF 12402 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 4. (PDF 11967 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 5. (PDF 11326 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 6. (PDF 10573 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 7. (PDF 10055 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 8. (PDF 9002 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 9. (PDF 8338 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 10. (PDF 8433 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 11. (PDF 8437 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 12. (PDF 8164 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 13. (PDF 6962 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 14. (PDF 6348 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 15. (PDF 5892 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 16. (PDF 5599 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 17. (PDF 4884 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 18. (PDF 4574 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 19. (PDF 3927 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 20. (PDF 3946 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 21. (PDF 2800 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome 22. (PDF 2872 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, chromosome X. (PDF 9589 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, Chimpanzee Sequence Y. (PDF 1636 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, Chimpanzee Sequence, PTR Chr22. (PDF 2732 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, Chimpanzee Sequence, PTR Specific Sequence. (PDF 41 kb)

Supplementary Figure S7

Chromosome views of chimpanzee and human segmental duplications, Chimpanzee Sequence, Unaligned PTR Sequence. (PDF 2175 kb)

Supplementary Table S1

Comparison of human and chimpanzee WSSD duplications (XLS 24 kb)

Supplementary Table S2

WSSD duplications and triallelic variants (XLS 18 kb)

Supplementary Table S3

FISH results for shared (CH) duplications (XLS 15 kb)

Supplementary Table S4

Chimpanzee-human array CGH vs. chimpanzee WSSD duplications (XLS 16 kb)

Supplementary Table S5

cDNA/ESTs with copy number verification from Fortna, A. et al. (XLS 19 kb)

Supplementary Table S6

Duplication statistics and duplication shadowing simulation results (XLS 207 kb)

Supplementary Table S7

Human specific gene duplications (XLS 16 kb)

Supplementary Table S8

Chimpanzee specific gene duplications (XLS 52 kb)

Supplementary Table S9

Genes differentially expressed and specifically duplicated in human or chimpanzee (XLS 35 kb)

Supplementary Table S10

Differentially expressed genes between human and chimpanzee vs. duplication regions (XLS 56 kb)

Supplementary Table S11

FISH results with chimpanzee-only duplications. (XLS 44 kb)

Supplementary Table S12

FISH results with chimpanzee-only duplications. (XLS 19 kb)

Supplementary Table S13

Human and chimpanzee single nucleotide variation in unique regions and duplication/unique transition regions. (XLS 15 kb)

Supplementary Table S14

Sequence identity of shared vs. human-only duplications (XLS 16 kb)

Supplementary Table S15

Regions where human copy # exceeds chimp copy# by >5 (XLS 131 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cheng, Z., Ventura, M., She, X. et al. A genome-wide comparison of recent chimpanzee and human segmental duplications. Nature 437, 88–93 (2005). https://doi.org/10.1038/nature04000

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature04000

This article is cited by

Comments

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.

Search

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