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PMID: 31624180 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Adaptive archaic introgression of copy number variants and the discovery of previously unknown human genes.

Science (New York, N.Y.) ·Vol. 366 ·No. 6463 ·2019-00-18

Hsieh P, Vollger MR, Dang V, Porubsky D, Baker C, Cantsilieris S, Hoekzema K, Lewis AP, Munson KM, Sorensen M, Kronenberg ZN, Murali S, Nelson BJ, Chiatante G, Maggiolini FAM, Blanché H, Underwood JG, Antonacci F, Deleuze JF, Eichler EE

Abstract

Copy number variants (CNVs) are subject to stronger selective pressure than single-nucleotide variants, but their roles in archaic introgression and adaptation have not been systematically investigated. We show that stratified CNVs are significantly associated with signatures of positive selection in Melanesians and provide evidence for adaptive introgression of large CNVs at chromosomes 16p11.2 and 8p21.3 from Denisovans and Neanderthals, respectively. Using long-read sequence data, we reconstruct the structure and complex evolutionary history of these polymorphisms and show that both encode positively selected genes absent from most human populations. Our results collectively suggest that large CNVs originating in archaic hominins and introgressed into modern humans have played an important role in local population adaptation and represent an insufficiently studied source of large-scale genetic variation.

MeSH Terms
Animals Chromosome Duplication Chromosomes, Human, Pair 16/genetics Chromosomes, Human, Pair 8/genetics DNA Copy Number Variations Evolution, Molecular Genetic Introgression Genome, Human Haplotypes Hominidae/genetics Humans Melanesia Models, Genetic Neanderthals/genetics Polymorphism, Genetic Selection, Genetic Whole Genome Sequencing
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Hsieh PingHsun ORCID
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Vollger Mitchell R ORCID
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Dang Vy ORCID
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Porubsky David
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Baker Carl
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Cantsilieris Stuart
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Hoekzema Kendra
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Lewis Alexandra P ORCID
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Munson Katherine M ORCID
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Sorensen Melanie ORCID
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Kronenberg Zev N
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Murali Shwetha
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA. | Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.
Nelson Bradley J
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Chiatante Giorgia
Dipartimento di Biologia, Università degli Studi di Bari "Aldo Moro," Bari, Italy.
Maggiolini Flavia Angela Maria ORCID
Dipartimento di Biologia, Università degli Studi di Bari "Aldo Moro," Bari, Italy.
Blanché Hélène ORCID
Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain, Paris, France.
Underwood Jason G
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA. | Pacific Biosciences (PacBio) of California, Inc., Menlo Park, CA, USA.
Antonacci Francesca
Dipartimento di Biologia, Università degli Studi di Bari "Aldo Moro," Bari, Italy.
Deleuze Jean-François
Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain, Paris, France.
Eichler Evan E ORCID
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA. [email protected]. | Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.aax2083
Email
[email protected]
Published
2019-00-18
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC6860971
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NHGRI NIH HHS · R01 HG002385 · United States
External Links
PubMed source DOI: 10.1126/science.aax2083 PMC Full Text View journal details
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