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A genome-wide comparison of recent chimpanzee and human segmental duplications

Nature volume 437, pages 8893 (01 September 2005) | Download Citation

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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%).

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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

Affiliations

  1. Howard Hughes Medical Institute, Department of Genome Sciences, University of Washington School of Medicine, 1705 NE Pacific Street, Seattle, Washington 98195, USA

    • Ze Cheng
    • , Xinwei She
    •  & Evan E. Eichler
  2. Department of Genetics and Microbiology, University of Bari, 70126 Bari, Italy

    • Mario Ventura
    •  & Mariano Rocchi
  3. Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, D-04103 Leipzig, Germany

    • Philipp Khaitovich
    •  & Svante Pääbo
  4. Washington University School of Medicine, 4444 Forest Park Blvd, St Louis, Missouri 63108, USA

    • Tina Graves
    •  & Richard K. Wilson
  5. BACPAC Resources, Children's Hospital of Oakland Research Institute, Bruce Lyon Memorial Research Building, Oakland, California 94609, USA

    • Kazutoyo Osoegawa
    •  & Pieter DeJong
  6. National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Building 38A, 8600 Rockville Pike, Bethesda, Maryland 20894, USA

    • Deanna Church

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Competing interests

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

Corresponding author

Correspondence to Evan E. Eichler.

Supplementary information

Word documents

  1. 1.

    Supplementary Methods

    Additional description of the methods used in this study.

  2. 2.

    Supplementary Figure Legends

    Text to accompany the below Supplementary Figures.

Powerpoint files

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    Supplementary Figures

    This file contains Supplementary Figures S1-S6, S8.

PDF files

  1. 1.

    Supplementary Figure S7

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

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 2.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 3.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 4.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 5.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 6.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 7.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 8.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 9.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 10.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 11.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 12.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 13.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 14.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 15.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 16.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 17.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 18.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 19.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 20.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 21.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome 22.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, chromosome X.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, Chimpanzee Sequence Y.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, Chimpanzee Sequence, PTR Chr22.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, Chimpanzee Sequence, PTR Specific Sequence.

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    Supplementary Figure S7

    Chromosome views of chimpanzee and human segmental duplications, Chimpanzee Sequence, Unaligned PTR Sequence.

Excel files

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    Supplementary Table S1

    Comparison of human and chimpanzee WSSD duplications

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    Supplementary Table S2

    WSSD duplications and triallelic variants

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    Supplementary Table S3

    FISH results for shared (CH) duplications

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    Supplementary Table S4

    Chimpanzee-human array CGH vs. chimpanzee WSSD duplications

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    Supplementary Table S5

    cDNA/ESTs with copy number verification from Fortna, A. et al.

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    Supplementary Table S6

    Duplication statistics and duplication shadowing simulation results

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    Supplementary Table S7

    Human specific gene duplications

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    Supplementary Table S8

    Chimpanzee specific gene duplications

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    Supplementary Table S9

    Genes differentially expressed and specifically duplicated in human or chimpanzee

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    Supplementary Table S10

    Differentially expressed genes between human and chimpanzee vs. duplication regions

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    Supplementary Table S11

    FISH results with chimpanzee-only duplications.

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    Supplementary Table S12

    FISH results with chimpanzee-only duplications.

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    Supplementary Table S13

    Human and chimpanzee single nucleotide variation in unique regions and duplication/unique transition regions.

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    Supplementary Table S14

    Sequence identity of shared vs. human-only duplications

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    Supplementary Table S15

    Regions where human copy # exceeds chimp copy# by >5

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https://doi.org/10.1038/nature04000

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