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PreprintCited by 73Genomic variations and chromosomal abnormalitiesChromosomal and Genetic VariationsGenome Rearrangement Algorithms

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Structurally divergent and recurrently mutated regions of primate genomes

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Mao, Yafei, Harvey, William T., Porubsky, David, Munson, Katherine M., Hoekzema, Kendra, Lewis, Alexandra P., Audano, Peter A., Rozanski, Allison, Yang, Xiangyu, Zhang, Shilong, Gordon, David S., Wei, Xiaoxi, Logsdon, Glennis A., Haukness, Marina, Dishuck, Philip C., Jeong, Hyeonsoo, del Rosario, Ricardo, Bauer, Vanessa L., Fattor, Will T., Wilkerson, Gregory K., Lu, Qing, Paten, Benedict, Feng, Guoping, Sawyer, Sara L., Warren, Wesley C., Carbone, Lucia, Eichler, Evan E.·2023·Cell
DOI 10.1101/2023.03.07.531415PMC PMC10947866

Preprint — published as 10.1016/j.cell.2024.01.052

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Abstract

To better understand the pattern of primate genome structural variation, we sequenced and assembled using multiple long-read sequencing technologies the genomes of eight nonhuman primate species, including New World monkeys (owl monkey and marmoset), Old World monkey (macaque), Asian apes (orangutan and gibbon), and African ape lineages (gorilla, bonobo, and chimpanzee). Compared to the human genome, we identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. Across 50 million years of primate evolution, we estimate that 819.47 Mbp or ~27% of the genome has been affected by SVs based on analysis of these primate lineages. We identify 1,607 structurally divergent regions (SDRs) wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost ( CARDs , ABCD7 , OLAH ) and new lineage-specific genes are generated (e.g., CKAP2 , NEK5 ) and have become targets of rapid chromosomal diversification and positive selection (e.g., RGPDs ). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species for the first time.

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Metadata

Authors
Mao, Y., Harvey, W. T., Porubsky, D., Munson, K. M., Hoekzema, K., Lewis, A. P., Audano, P. A., Rozanski, A., Yang, X., Zhang, S., Gordon, D. S., Wei, X., Logsdon, G. A., Haukness, M., Dishuck, P. C., Jeong, H., del Rosario, R., Bauer, V. L., Fattor, W. T., Wilkerson, G. K., Lu, Q., Paten, B., Feng, G., Sawyer, S. L., Warren, W. C., Carbone, L., & Eichler, E. E.
Affiliations
  • Shanghai Jiao Tong University (CN)
  • University of Washington (US)
  • Howard Hughes Medical Institute (US)
  • University of California, Santa Cruz (US)
  • Broad Institute (US)
  • University of Colorado Boulder (US)
  • The University of Texas MD Anderson Cancer Center (US)
  • University of Missouri (US)
  • Oregon National Primate Research Center (US)
Corresponding author
  • Mao, Yafei
  • Eichler, Evan E.
ORCID
Venue
Cell
Publisher
openRxiv
Published
2023-03-07
Volume
187
Issue
6
Pages
1547-1562.e13
ISSN
0092-8674 (ISSN-L)
DOI
10.1101/2023.03.07.531415
PMC
PMC10947866
OpenAlex
W4392302376
Cited by
73
References
1
Citations by year
2026: 18 · 2025: 32 · 2024: 18 · 2023: 5
FWCI
17.99
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cell (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • Howard Hughes Medical Institute
  • National Natural Science Foundation of China (82001372, WH510363001)
  • Shanghai Jiao Tong University
  • National Institutes of Health (OD-011092, R01OD034046, P51OD011092)
  • Oregon National Primate Research Center (P51OD011092, OD011092)
  • National Institute on Drug Abuse (DP1DA046108)
  • National Human Genome Research Institute (R01HG010485, R01HG010333, U24HG009081, U01HG010961, R01HG002385, U24HG011853, U24HG007234, R01HG010169, U41HG010972)
  • National Institute of General Medical Sciences (K99GM147352, R00GM147352)
  • National Institute of Allergy and Infectious Diseases (R01AI137011, DP1AI175471)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
Keywords
structural variants, primate genomes, gene loss, regulatory elements, positive selection, gene family evolution, paralogs, long-read genome assembly, chimpanzees, bonobos, gorillas, orangutans, gibbons, macaque, owl monkey, marmoset

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