Structurally divergent and recurrently mutated regions of primate genomes

Yafei Mao; William T Harvey; David Porubsky; Katherine M Munson; Kendra Hoekzema; Alexandra P Lewis; Peter A Audano; Allison Rozanski; Xiangyu Yang; Shilong Zhang; DongAhn Yoo; David S Gordon; Tyler Fair; Xiaoxi Wei; Glennis A Logsdon; Marina Haukness; Philip C Dishuck; Hyeonsoo Jeong; Ricardo Del Rosario; Vanessa L Bauer; Will T Fattor; Gregory K Wilkerson; Yuxiang Mao; Yongyong Shi; Qiang Sun; Qing Lu; Benedict Paten; Trygve E Bakken; Alex A Pollen; Guoping Feng; Sara L Sawyer; Wesley C Warren; Lucia Carbone; Evan E Eichler

doi:10.1016/j.cell.2024.01.052

Structurally divergent and recurrently mutated regions of primate genomes

Cell. 2024 Mar 14;187(6):1547-1562.e13. doi: 10.1016/j.cell.2024.01.052. Epub 2024 Feb 29.

Authors

Yafei Mao¹, William T Harvey², David Porubsky², Katherine M Munson², Kendra Hoekzema², Alexandra P Lewis², Peter A Audano², Allison Rozanski², Xiangyu Yang³, Shilong Zhang³, DongAhn Yoo², David S Gordon⁴, Tyler Fair⁵, Xiaoxi Wei³, Glennis A Logsdon², Marina Haukness⁶, Philip C Dishuck², Hyeonsoo Jeong², Ricardo Del Rosario⁷, Vanessa L Bauer⁸, Will T Fattor⁸, Gregory K Wilkerson⁹, Yuxiang Mao¹⁰, Yongyong Shi¹¹, Qiang Sun¹⁰, Qing Lu³, Benedict Paten⁶, Trygve E Bakken¹², Alex A Pollen¹³, Guoping Feng⁷, Sara L Sawyer⁸, Wesley C Warren¹⁴, Lucia Carbone¹⁵, Evan E Eichler¹⁶

Affiliations

¹ Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. Electronic address: yafmao@sjtu.edu.cn.
² Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
³ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
⁴ Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.
⁵ Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
⁶ UC Santa Cruz Genomics Institute, University of California, Santa Cruz, Santa Cruz, CA, USA.
⁷ McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁸ BioFrontiers Institute, Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Bouder, CO, USA.
⁹ Department of Veterinary Sciences, Michale E. Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Bastrop, TX, USA; Department of Clinical Sciences, North Carolina State University, Raleigh, NC, USA.
¹⁰ Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science & Intelligence Technology, Chinese Academy of Sciences, Shanghai, China; Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai, China.
¹¹ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China; Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science & Intelligence Technology, Chinese Academy of Sciences, Shanghai, China; Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai, China.
¹² Allen Institute for Brain Science, Seattle, WA, USA.
¹³ Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
¹⁴ Department of Animal Sciences, Bond Life Sciences Center, University of Missouri, Columbia, MO, USA; Department of Surgery, School of Medicine, University of Missouri, Columbia, MO, USA; Institute of Data Science and Informatics, University of Missouri, Columbia, MO, USA.
¹⁵ Department of Medicine, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA; Division of Genetics, Oregon National Primate Research Center, Beaverton, OR, USA; Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA; Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, OR, USA.
¹⁶ Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA. Electronic address: eee@gs.washington.edu.

PMID: 38428424
PMCID: PMC10947866 (available on 2025-03-14)
DOI: 10.1016/j.cell.2024.01.052

Abstract

We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, and marmoset. 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. We estimate that 819.47 Mbp or ∼27% of the genome has been affected by SVs across primate evolution. We identify 1,607 structurally divergent regions wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (e.g., CARD, C4, and OLAH gene families) and additional lineage-specific genes are generated (e.g., CKAP2, VPS36, ACBD7, and NEK5 paralogs), becoming targets of rapid chromosomal diversification and positive selection (e.g., RGPD gene family). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species.

Keywords: NPHP1 and Joubert syndrome; RGPD gene family; adaptive evolution; comparative genomics; duplicated genes; evolutionary medicine; human diseases; long-read sequencing; primate evolution.

MeSH terms

Animals
Base Sequence
Biological Evolution
Genome*
Genomic Structural Variation
Humans
Primates* / classification
Primates* / genetics
Sequence Analysis, DNA

Abstract

MeSH terms

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