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

Ping Hsun Hsieh; Mitchell R. Vollger; Vy Dang; David Porubsky; Carl Baker; Stuart Cantsilieris; Kendra Hoekzema; Alexandra P. Lewis; Katherine M. Munson; Melanie Sorensen; Zev N. Kronenberg; Shwetha Murali; Bradley J. Nelson; Giorgia Chiatante; Flavia Angela Maria Maggiolini; Hélène Blanché; Jason G. Underwood; Francesca Antonacci; Jean François Deleuze; Evan E. Eichler

doi:10.1126/science.aax2083

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

Ping Hsun Hsieh, Mitchell R. Vollger, Vy Dang, David Porubsky, Carl Baker, Stuart Cantsilieris, Kendra Hoekzema, Alexandra P. Lewis, Katherine M. Munson, Melanie Sorensen, Zev N. Kronenberg, Shwetha Murali, Bradley J. Nelson, Giorgia Chiatante, Flavia Angela Maria Maggiolini, Hélène Blanché, Jason G. Underwood, Francesca Antonacci, Jean François Deleuze, Evan E. Eichler

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

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.

Original language	English (US)
Article number	eaax2083
Journal	Science
Volume	366
Issue number	6463
DOIs	https://doi.org/10.1126/science.aax2083
State	Published - Oct 18 2019
Externally published	Yes

Bibliographical note

Funding Information:
We thank J. Friedlaender, M. Brilliant, and T. Carter for providing access to the Papua New Guinea DNA samples housed at the Marshfield Clinic Research Institute in the Center for Precision Medicine Research; J. Akey for providing additional Papuan DNA samples; T. Brown for assistance in editing this manuscript; J. Friedlaender for helpful comments in the preparation of this manuscript; and D. S. Gordon for help with submitting our data to the NCBI database. This work was supported, in part, by U.S. National Institutes of Health (NIH) grant R01HG002385 to E.E.E. S.C. was supported by a National Health and Medical Research Council (NHMRC) C. J. Martin Biomedical Fellowship (1073726). E.E.E. is an investigator of the Howard Hughes Medical Institute.

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Copyright © 2019 The Authors,

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Hsieh, P. H., Vollger, M. R., Dang, V., Porubsky, D., Baker, C., Cantsilieris, S., Hoekzema, K., Lewis, A. P., Munson, K. M., Sorensen, M., Kronenberg, Z. N., Murali, S., Nelson, B. J., Chiatante, G., Maggiolini, F. A. M., Blanché, H., Underwood, J. G., Antonacci, F., Deleuze, J. F., & Eichler, E. E. (2019). Adaptive archaic introgression of copy number variants and the discovery of previously unknown human genes. Science, 366(6463), Article eaax2083. https://doi.org/10.1126/science.aax2083

Hsieh, PH, 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 2019, 'Adaptive archaic introgression of copy number variants and the discovery of previously unknown human genes', Science, vol. 366, no. 6463, eaax2083. https://doi.org/10.1126/science.aax2083

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title = "Adaptive archaic introgression of copy number variants and the discovery of previously unknown human genes",

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.",

author = "Hsieh, {Ping Hsun} and Vollger, {Mitchell R.} and Vy Dang and David Porubsky and Carl Baker and Stuart Cantsilieris and Kendra Hoekzema and Lewis, {Alexandra P.} and Munson, {Katherine M.} and Melanie Sorensen and Kronenberg, {Zev N.} and Shwetha Murali and Nelson, {Bradley J.} and Giorgia Chiatante and Maggiolini, {Flavia Angela Maria} and H{\'e}l{\`e}ne Blanch{\'e} and Underwood, {Jason G.} and Francesca Antonacci and Deleuze, {Jean Fran{\c c}ois} and Eichler, {Evan E.}",

note = "Funding Information: We thank J. Friedlaender, M. Brilliant, and T. Carter for providing access to the Papua New Guinea DNA samples housed at the Marshfield Clinic Research Institute in the Center for Precision Medicine Research; J. Akey for providing additional Papuan DNA samples; T. Brown for assistance in editing this manuscript; J. Friedlaender for helpful comments in the preparation of this manuscript; and D. S. Gordon for help with submitting our data to the NCBI database. This work was supported, in part, by U.S. National Institutes of Health (NIH) grant R01HG002385 to E.E.E. S.C. was supported by a National Health and Medical Research Council (NHMRC) C. J. Martin Biomedical Fellowship (1073726). E.E.E. is an investigator of the Howard Hughes Medical Institute. Publisher Copyright: Copyright {\textcopyright} 2019 The Authors,",

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doi = "10.1126/science.aax2083",

language = "English (US)",

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T1 - Adaptive archaic introgression of copy number variants and the discovery of previously unknown human genes

AU - Hsieh, Ping Hsun

AU - Vollger, Mitchell R.

AU - Dang, Vy

AU - Porubsky, David

AU - Baker, Carl

AU - Cantsilieris, Stuart

AU - Hoekzema, Kendra

AU - Lewis, Alexandra P.

AU - Munson, Katherine M.

AU - Sorensen, Melanie

AU - Kronenberg, Zev N.

AU - Murali, Shwetha

AU - Nelson, Bradley J.

AU - Chiatante, Giorgia

AU - Maggiolini, Flavia Angela Maria

AU - Blanché, Hélène

AU - Underwood, Jason G.

AU - Antonacci, Francesca

AU - Deleuze, Jean François

AU - Eichler, Evan E.

N1 - Funding Information: We thank J. Friedlaender, M. Brilliant, and T. Carter for providing access to the Papua New Guinea DNA samples housed at the Marshfield Clinic Research Institute in the Center for Precision Medicine Research; J. Akey for providing additional Papuan DNA samples; T. Brown for assistance in editing this manuscript; J. Friedlaender for helpful comments in the preparation of this manuscript; and D. S. Gordon for help with submitting our data to the NCBI database. This work was supported, in part, by U.S. National Institutes of Health (NIH) grant R01HG002385 to E.E.E. S.C. was supported by a National Health and Medical Research Council (NHMRC) C. J. Martin Biomedical Fellowship (1073726). E.E.E. is an investigator of the Howard Hughes Medical Institute. Publisher Copyright: Copyright © 2019 The Authors,

PY - 2019/10/18

Y1 - 2019/10/18

N2 - 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.

AB - 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.

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

Abstract

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