Adaptive eQTLs reveal the evolutionary impacts of pleiotropy and tissue-specificity while contributing to health and disease.
Adaptive eQTLs reveal the evolutionary impacts of pleiotropy and tissue-specificity while contributing to health and disease.
复制标题
DOI：
10.1016/j.xhgg.2021.100083
复制
发表时间：
2022-01-13
期刊：
影响因子：
--
通讯作者：
Lachance J
中科院分区：
文献类型：
--
作者：
Quiver MH;Lachance J
最近在人类中鉴定了大量的表达数量性状基因座（eQTL），并且这些调节变体中的许多在群体之间具有大的等位基因频率差异。在这里，我们进行了选择的全基因组扫描以识别适应性eQTL（即，具有大群体分支统计量的eQTL）。然后，我们测试了组织多效性是否会影响eQTL是否更有可能或更少地具有适应性，并确定了在过去10万年中一直是积极选择的关键目标的组织。最常见的适应性eQTL离群值包括rs1043809、rs66899053和rs2814778（与疟疾抗性相关的SNP）。我们发现eQTL的效应大小与群体分支统计量呈负相关，适应性eQTL影响的组织是非适应性eQTL的三分之二。由于eQTL的组织宽度可以被视为多效性的量度，因此这些结果意味着多效性抑制适应。适应性eQTL的比例因组织而异，我们发现调节睾丸，甲状腺，血液或阳光暴露的皮肤中表达的eQTL富含正选择的特征。相比之下，调节大脑或雌性特异性组织中表达的eQTL相对缺乏适应性离群值。选择扫描还揭示了许多适应性eQTL与疾病相关基因座紧密连锁。总之，我们的研究结果表明，eQTL在最近的人类进化中发挥了重要作用。
Large numbers of expression quantitative trait loci (eQTLs) have recently been identified in humans, and many of these regulatory variants have large allele frequency differences between populations. Here, we conducted genome-wide scans of selection to identify adaptive eQTLs (i.e., eQTLs with large population branch statistics). We then tested if tissue pleiotropy affects whether eQTLs are more or less likely to be adaptive and identified tissues that have been key targets of positive selection during the last 100,000 years. Top adaptive eQTL outliers include rs1043809, rs66899053, and rs2814778 (a SNP that is associated with malaria resistance). We found that effect sizes of eQTLs were negatively correlated with population branch statistics and that adaptive eQTLs affect two-thirds as many tissues as do non-adaptive eQTLs. Because the tissue breadth of an eQTL can be viewed as a measure of pleiotropy, these results imply that pleiotropy inhibits adaptation. The proportion of eQTLs that are adaptive varies by tissue, and we found that eQTLs that regulate expression in testis, thyroid, blood, or sun-exposed skin are enriched for signatures of positive selection. By contrast, eQTLs that regulate expression in the cerebrum or female-specific tissues have a relative lack of adaptive outliers. Scans of selections also reveal that many adaptive eQTLs are closely linked to disease-associated loci. Taken together, our results indicate that eQTLs have played an important role in recent human evolution.
登录
查看更多内容
影响因子：
7
作者：
Guschanski K;Warnefors M;Kaessmann H
通讯作者：
Kaessmann H
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
1.8
作者：
Agresti, A;Coull, BA
通讯作者：
Coull, BA
DOI：
10.4061/2011/274975
发表时间：
2011-01-01
期刊：
International Journal of Evolutionary Biology
影响因子：
--
作者：
Grassa, Christopher J.;Kulathinal, Rob J.
通讯作者：
Kulathinal, Rob J.