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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%).

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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.

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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.

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Correspondence to Evan E. Eichler.

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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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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)

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

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

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

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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)

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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

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