A signature of Neanderthal introgression on molecular mechanisms of environmental responses.

Ancient human migrations led to the settlement of population groups in varied environmental contexts worldwide. The extent to which adaptation to local environments has shaped human genetic diversity is a longstanding question in human evolution. Recent studies have suggested that introgression of a...

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Autores principales:	Anthony S Findley, Xinjun Zhang, Carly Boye, Yen Lung Lin, Cynthia A Kalita, Luis Barreiro, Kirk E Lohmueller, Roger Pique-Regi, Francesca Luca
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/ab39d80af0ec42f88e98b430921786b2
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spelling	oai:doaj.org-article:ab39d80af0ec42f88e98b430921786b22021-12-02T20:03:02ZA signature of Neanderthal introgression on molecular mechanisms of environmental responses.1553-73901553-740410.1371/journal.pgen.1009493https://doaj.org/article/ab39d80af0ec42f88e98b430921786b22021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009493https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Ancient human migrations led to the settlement of population groups in varied environmental contexts worldwide. The extent to which adaptation to local environments has shaped human genetic diversity is a longstanding question in human evolution. Recent studies have suggested that introgression of archaic alleles in the genome of modern humans may have contributed to adaptation to environmental pressures such as pathogen exposure. Functional genomic studies have demonstrated that variation in gene expression across individuals and in response to environmental perturbations is a main mechanism underlying complex trait variation. We considered gene expression response to in vitro treatments as a molecular phenotype to identify genes and regulatory variants that may have played an important role in adaptations to local environments. We investigated if Neanderthal introgression in the human genome may contribute to the transcriptional response to environmental perturbations. To this end we used eQTLs for genes differentially expressed in a panel of 52 cellular environments, resulting from 5 cell types and 26 treatments, including hormones, vitamins, drugs, and environmental contaminants. We found that SNPs with introgressed Neanderthal alleles (N-SNPs) disrupt binding of transcription factors important for environmental responses, including ionizing radiation and hypoxia, and for glucose metabolism. We identified an enrichment for N-SNPs among eQTLs for genes differentially expressed in response to 8 treatments, including glucocorticoids, caffeine, and vitamin D. Using Massively Parallel Reporter Assays (MPRA) data, we validated the regulatory function of 21 introgressed Neanderthal variants in the human genome, corresponding to 8 eQTLs regulating 15 genes that respond to environmental perturbations. These findings expand the set of environments where archaic introgression may have contributed to adaptations to local environments in modern humans and provide experimental validation for the regulatory function of introgressed variants.Anthony S FindleyXinjun ZhangCarly BoyeYen Lung LinCynthia A KalitaLuis BarreiroKirk E LohmuellerRoger Pique-RegiFrancesca LucaPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 9, p e1009493 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Anthony S Findley Xinjun Zhang Carly Boye Yen Lung Lin Cynthia A Kalita Luis Barreiro Kirk E Lohmueller Roger Pique-Regi Francesca Luca A signature of Neanderthal introgression on molecular mechanisms of environmental responses.
description	Ancient human migrations led to the settlement of population groups in varied environmental contexts worldwide. The extent to which adaptation to local environments has shaped human genetic diversity is a longstanding question in human evolution. Recent studies have suggested that introgression of archaic alleles in the genome of modern humans may have contributed to adaptation to environmental pressures such as pathogen exposure. Functional genomic studies have demonstrated that variation in gene expression across individuals and in response to environmental perturbations is a main mechanism underlying complex trait variation. We considered gene expression response to in vitro treatments as a molecular phenotype to identify genes and regulatory variants that may have played an important role in adaptations to local environments. We investigated if Neanderthal introgression in the human genome may contribute to the transcriptional response to environmental perturbations. To this end we used eQTLs for genes differentially expressed in a panel of 52 cellular environments, resulting from 5 cell types and 26 treatments, including hormones, vitamins, drugs, and environmental contaminants. We found that SNPs with introgressed Neanderthal alleles (N-SNPs) disrupt binding of transcription factors important for environmental responses, including ionizing radiation and hypoxia, and for glucose metabolism. We identified an enrichment for N-SNPs among eQTLs for genes differentially expressed in response to 8 treatments, including glucocorticoids, caffeine, and vitamin D. Using Massively Parallel Reporter Assays (MPRA) data, we validated the regulatory function of 21 introgressed Neanderthal variants in the human genome, corresponding to 8 eQTLs regulating 15 genes that respond to environmental perturbations. These findings expand the set of environments where archaic introgression may have contributed to adaptations to local environments in modern humans and provide experimental validation for the regulatory function of introgressed variants.
format	article
author	Anthony S Findley Xinjun Zhang Carly Boye Yen Lung Lin Cynthia A Kalita Luis Barreiro Kirk E Lohmueller Roger Pique-Regi Francesca Luca
author_facet	Anthony S Findley Xinjun Zhang Carly Boye Yen Lung Lin Cynthia A Kalita Luis Barreiro Kirk E Lohmueller Roger Pique-Regi Francesca Luca
author_sort	Anthony S Findley
title	A signature of Neanderthal introgression on molecular mechanisms of environmental responses.
title_short	A signature of Neanderthal introgression on molecular mechanisms of environmental responses.
title_full	A signature of Neanderthal introgression on molecular mechanisms of environmental responses.
title_fullStr	A signature of Neanderthal introgression on molecular mechanisms of environmental responses.
title_full_unstemmed	A signature of Neanderthal introgression on molecular mechanisms of environmental responses.
title_sort	signature of neanderthal introgression on molecular mechanisms of environmental responses.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/ab39d80af0ec42f88e98b430921786b2
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A signature of Neanderthal introgression on molecular mechanisms of environmental responses.

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