Patterns of recent natural selection on genetic loci associated with sexually differentiated human body size and shape phenotypes.
Patterns of recent natural selection on genetic loci associated with sexually differentiated human body size and shape phenotypes.
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DOI：
10.1371/journal.pgen.1009562
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发表时间：
2021-06
期刊：
影响因子：
4.5
通讯作者：
Perry GH
中科院分区：
文献类型：
--
作者：
Arner AM;Grogan KE;Grabowski M;Reyes-Centeno H;Perry GH
人类体型和形状表型的性别差异水平被假设为在农业转型后适应性地降低，作为对相对更平等的劳动分工和新技术采用的进化反应的一部分。在这项研究中，我们通过研究与五种性分化人类表型相关的遗传变异来验证这一假设：身高、体重、臀围、体脂百分比和腰围。我们首先分析了英国生物库个体（约194，000名女性和约167，000名男性）的全基因组关联（GWAS）结果，以确定总计114，199个单核苷酸多态性（SNP），这些SNP与女性、男性或两性中至少一种研究表型显著相关（P<5x 10 -8）。从这些基因座中，我们确定了3，016个SNP（2.6%），在低错误发现率（FDR<0.001）下，女性和男性特异性GWAS结果之间的关联强度存在显著差异。与通常与表型相关但与性别差异无关的SNP相比，在性分化中具有已知作用的基因显著富集为与这些SNP中的一个或多个共定位（2.73倍富集;排列检验; P = 0.0041）。我们还证实，在具有较强关联值的性别中，所鉴定的变体与更大的表型效应大小不成比例地相关。然后，我们使用了单例密度得分统计，它量化了最近的（在过去的~3,000年内;英国农业采用后）多基因性状背后的等位基因频率的变化，以确定最近与女性体脂百分比较高相关的等位基因的正选择特征（排列检验; P = 0.0038; FDR = 0.0380），与性别差异减少假设预测的结果相反。否则，我们没有发现任何其他性状的性别差异相关等位基因的正选择的证据。总的来说，我们的研究结果挑战了长期存在的假设，即从狩猎和采集到农业的生存过渡后，性别差异自适应地减少了。关于人类性别差异的进化历史，在数量上的身体大小和形状表型方面存在着不确定性。在这项研究中，我们确定了数千个遗传位点，差异影响身体大小和形状性状变异的女性和男性之间使用大样本的英国生物银行个人。在确认了这些基因座的生物学意义后，我们使用群体基因组学方法研究了这些基因座在该群体中最近（过去约3,000年）的进化历史。我们观察到女性中与更高体脂百分比相关的等位基因频率显著增加。这一结果与长期存在的假设相矛盾，即在从狩猎和采集到农业的生存过渡之后，性别差异已经适应性地减少了。
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. There is uncertainty regarding the evolutionary history of human sex differences for quantitative body size and shape phenotypes. In this study we identified thousands of genetic loci that differentially impact body size and shape trait variation between females and males using a large sample of UK Biobank individuals. After confirming the biological plausibility of these loci, we used a population genomics approach to study the recent (over the past ~3,000 years) evolutionary histories of these loci in this population. We observed significant increases in the frequencies of alleles associated with greater body fat percentage in females. This result is contradictory to longstanding hypotheses that sex differences have adaptively decreased following subsistence transitions from hunting and gathering to agriculture.
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