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Cited by 72Genomic variations and chromosomal abnormalitiesGenome Rearrangement AlgorithmsChromosomal and Genetic Variations

Recurrent inversion toggling and great ape genome evolution

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Porubsky, David, Sanders, Ashley D., Höps, Wolfram, Hsieh, PingHsun, Sulovari, Arvis, Li, Ruiyang, Mercuri, Ludovica, Sorensen, Melanie +9 more·2020·Nature Genetics
DOI 10.1038/s41588-020-0646-xPMC PMC7415573
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Abstract

Inversions play an important role in disease and evolution but are difficult to characterize because their breakpoints map to large repeats. We increased by sixfold the number (n = 1,069) of previously reported great ape inversions by using single-cell DNA template strand and long-read sequencing. We find that the X chromosome is most enriched (2.5-fold) for inversions, on the basis of its size and duplication content. There is an excess of differentially expressed primate genes near the breakpoints of large (>100 kilobases (kb)) inversions but not smaller events. We show that when great ape lineage-specific duplications emerge, they preferentially (approximately 75%) occur in an inverted orientation compared to that at their ancestral locus. We construct megabase-pair scale haplotypes for individual chromosomes and identify 23 genomic regions that have recurrently toggled between a direct and an inverted state over 15 million years. The direct orientation is most frequently the derived state for human polymorphisms that predispose to recurrent copy number variants associated with neurodevelopmental disease.

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  • Inversions bringing two pairs of loci into proximity occur at inversion rates ranging between 0.4 and 7 fixed inversions per million years in animal clades.

    “These changes are limited by other rearrangement mechanisms, like inversions bringing two pairs of loci into proximity to one another, occurring at inversion rates ranging between 0.4 and 7 fixed inversions per million years in animal clades (176–179).”

    From Topological Approaches in Animal Comparative Genomics (2026) · cites this paper as [176]

    The Results section (‘Phylogenetic reconstruction’; page unavailable) estimates approximately 7 fixed autosomal inversions per million years in great apes. It does not establish a range beginning at 0.4 across animal clades or say that these inversions bring two pairs of loci into proximity. (LLM, conf=0.86)

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Authors
Porubsky, D., Sanders, A. D., Höps, W., Hsieh, P., Sulovari, A., Li, R., Mercuri, L., Sorensen, M., Murali, S. C., Gordon, D., Cantsilieris, S., Pollen, A. A., Ventura, M., Antonacci, F., Marschall, T., Korbel, J. O., & Eichler, E. E.
Affiliations
  • European Molecular Biology Laboratory (DE)
  • University of Washington (US)
  • University of Bari Aldo Moro (IT)
  • Howard Hughes Medical Institute (US)
  • The University of Melbourne (AU)
  • University of California, San Francisco (US)
  • Heinrich Heine University Düsseldorf (DE)
Corresponding author
Eichler, Evan E.
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2020-06-15
Volume
52
Issue
8
Pages
849-858
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/s41588-020-0646-x
PMC
PMC7415573
OpenAlex
W3035437122
Cited by
72
References
8
Citations by year
2026: 3 · 2025: 16 · 2024: 12 · 2023: 13 · 2022: 10 · 2021: 14 · 2020: 4
FWCI
6.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, other-oa)
Funders
  • Howard Hughes Medical Institute
  • Alexander von Humboldt-Stiftung
  • European Molecular Biology Laboratory
  • National Institutes of Health (HG000035)
  • Medical Research Council
  • National Health and Medical Research Council (1073726)
  • National Human Genome Research Institute (K99HG011041, R01HG002385, R01HG010169, T32HG000035)
  • H2020 European Research Council (773026)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
chromosomal inversions, primate genome evolution, X chromosome, haplotypes, copy number variation, neurodevelopmental disorders, long-read sequencing, inversion breakpoints
MeSH terms
Animals, Chromosomes, Female, Haplotypes, Humans, Chromosome Inversion, Male, Hominidae, Genome, Evolution, Molecular, DNA Copy Number Variations

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