Patterns of recent natural selection on genetic loci associated with sexually differentiated human body size and shape phenotypes.

Levels of sex differences for human body size and shape phenotypes are hypothesized to have adaptively reduced following the agricultural transition as part of an evolutionary response to relatively more equal divisions of labor and new technology adoption. In this study, we tested this hypothesis b...

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Autores principales:	Audrey M Arner, Kathleen E Grogan, Mark Grabowski, Hugo Reyes-Centeno, George H Perry
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/f84794ce62a14410bfda004584072fad
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spelling	oai:doaj.org-article:f84794ce62a14410bfda004584072fad2021-12-02T20:02:43ZPatterns of recent natural selection on genetic loci associated with sexually differentiated human body size and shape phenotypes.1553-73901553-740410.1371/journal.pgen.1009562https://doaj.org/article/f84794ce62a14410bfda004584072fad2021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009562https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Levels of sex differences for human body size and shape phenotypes are hypothesized to have adaptively reduced following the agricultural transition as part of an evolutionary response to relatively more equal divisions of labor and new technology adoption. In this study, we tested this hypothesis by studying genetic variants associated with five sexually differentiated human phenotypes: height, body mass, hip circumference, body fat percentage, and waist circumference. We first analyzed genome-wide association (GWAS) results for UK Biobank individuals (~194,000 females and ~167,000 males) to identify a total of 114,199 single nucleotide polymorphisms (SNPs) significantly associated with at least one of the studied phenotypes in females, males, or both sexes (P<5x10-8). From these loci we then identified 3,016 SNPs (2.6%) with significant differences in the strength of association between the female- and male-specific GWAS results at a low false-discovery rate (FDR<0.001). Genes with known roles in sexual differentiation are significantly enriched for co-localization with one or more of these SNPs versus SNPs associated with the phenotypes generally but not with sex differences (2.73-fold enrichment; permutation test; P = 0.0041). We also confirmed that the identified variants are disproportionately associated with greater phenotype effect sizes in the sex with the stronger association value. We then used the singleton density score statistic, which quantifies recent (within the last ~3,000 years; post-agriculture adoption in Britain) changes in the frequencies of alleles underlying polygenic traits, to identify a signature of recent positive selection on alleles associated with greater body fat percentage in females (permutation test; P = 0.0038; FDR = 0.0380), directionally opposite to that predicted by the sex differences reduction hypothesis. Otherwise, we found no evidence of positive selection for sex difference-associated alleles for any other trait. Overall, our results challenge the longstanding hypothesis that sex differences adaptively decreased following subsistence transitions from hunting and gathering to agriculture.Audrey M ArnerKathleen E GroganMark GrabowskiHugo Reyes-CentenoGeorge H PerryPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 6, p e1009562 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Audrey M Arner Kathleen E Grogan Mark Grabowski Hugo Reyes-Centeno George H Perry Patterns of recent natural selection on genetic loci associated with sexually differentiated human body size and shape phenotypes.
description	Levels of sex differences for human body size and shape phenotypes are hypothesized to have adaptively reduced following the agricultural transition as part of an evolutionary response to relatively more equal divisions of labor and new technology adoption. In this study, we tested this hypothesis by studying genetic variants associated with five sexually differentiated human phenotypes: height, body mass, hip circumference, body fat percentage, and waist circumference. We first analyzed genome-wide association (GWAS) results for UK Biobank individuals (~194,000 females and ~167,000 males) to identify a total of 114,199 single nucleotide polymorphisms (SNPs) significantly associated with at least one of the studied phenotypes in females, males, or both sexes (P<5x10-8). From these loci we then identified 3,016 SNPs (2.6%) with significant differences in the strength of association between the female- and male-specific GWAS results at a low false-discovery rate (FDR<0.001). Genes with known roles in sexual differentiation are significantly enriched for co-localization with one or more of these SNPs versus SNPs associated with the phenotypes generally but not with sex differences (2.73-fold enrichment; permutation test; P = 0.0041). We also confirmed that the identified variants are disproportionately associated with greater phenotype effect sizes in the sex with the stronger association value. We then used the singleton density score statistic, which quantifies recent (within the last ~3,000 years; post-agriculture adoption in Britain) changes in the frequencies of alleles underlying polygenic traits, to identify a signature of recent positive selection on alleles associated with greater body fat percentage in females (permutation test; P = 0.0038; FDR = 0.0380), directionally opposite to that predicted by the sex differences reduction hypothesis. Otherwise, we found no evidence of positive selection for sex difference-associated alleles for any other trait. Overall, our results challenge the longstanding hypothesis that sex differences adaptively decreased following subsistence transitions from hunting and gathering to agriculture.
format	article
author	Audrey M Arner Kathleen E Grogan Mark Grabowski Hugo Reyes-Centeno George H Perry
author_facet	Audrey M Arner Kathleen E Grogan Mark Grabowski Hugo Reyes-Centeno George H Perry
author_sort	Audrey M Arner
title	Patterns of recent natural selection on genetic loci associated with sexually differentiated human body size and shape phenotypes.
title_short	Patterns of recent natural selection on genetic loci associated with sexually differentiated human body size and shape phenotypes.
title_full	Patterns of recent natural selection on genetic loci associated with sexually differentiated human body size and shape phenotypes.
title_fullStr	Patterns of recent natural selection on genetic loci associated with sexually differentiated human body size and shape phenotypes.
title_full_unstemmed	Patterns of recent natural selection on genetic loci associated with sexually differentiated human body size and shape phenotypes.
title_sort	patterns of recent natural selection on genetic loci associated with sexually differentiated human body size and shape phenotypes.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/f84794ce62a14410bfda004584072fad
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Patterns of recent natural selection on genetic loci associated with sexually differentiated human body size and shape phenotypes.

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