Local Adaptation of Sun-Exposure-Dependent Gene Expression Regulation in Human Skin.
Local Adaptation of Sun-Exposure-Dependent Gene Expression Regulation in Human Skin.
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DOI：
10.1371/journal.pgen.1006382
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发表时间：
2016-10
期刊：
影响因子：
4.5
通讯作者：
Fraser HB
中科院分区：
文献类型：
--
作者：
Kita R;Fraser HB
阳光照射是人类进化研究中的一个关键环境变量。一些皮肤色素沉着基因是正选择的经典例子，表明阳光照射显着影响了全球基因组变异。在这里，我们研究遗传变异和阳光照射之间的相互作用，以及它如何影响基因表达调控。利用 607 个人类皮肤样本的 RNA-Seq 数据，我们鉴定了数千个在阳光照射皮肤和非阳光照射皮肤之间差异表达的转录本。然后我们测试了遗传变异是否会影响每个人对阳光照射的基因表达反应。我们的分析揭示了 10 个阳光照射依赖性基因表达数量性状位点 (se-eQTL)，包括参与皮肤色素沉着 (SLC45A2) 和表皮分化 (RASSF9) 的基因。不同人群中 RASSF9 se-eQTL 的等位基因频率与这些人群所经历的太阳辐射强度相关，表明当地对不同阳光水平的适应。这些结果提供了阳光照射依赖性调节变异的第一个例子，并表明这种变异有助于最近的人类适应。世界各地不同程度的阳光照射极大地影响了人类的进化。先前的分析发现，一些皮肤色素沉着基因在整个人类历史中存在强大的进化压力，表现为不同人群基因组变异频率的巨大差异。但即使在不同人群中，个体对阳光照射的反应也不同，这表明除了不同人群皮肤色素沉着的主要差异之外，还存在差异。在这里，我们研究了遗传变异是否与欧洲人对阳光照射的反应相关。为了测量反应，我们分析了阳光照射和非阳光照射皮肤的基因表达，并确定了与附近基因的阳光照射反应相关的十种遗传变异。其中一种基因变异与 RASSF9 基因的阳光照射反应相关，显示出人类对太阳辐射的适应能力。这些证据共同表明，基因表达的调节受到阳光照射的影响，并且阳光照射对 RASSF9 表达的依赖效应可能对人类健康产生影响。据我们所知，这是第一个具有人类适应证据的环境依赖性调节变异的例子。
Sun-exposure is a key environmental variable in the study of human evolution. Several skin-pigmentation genes serve as classical examples of positive selection, suggesting that sun-exposure has significantly shaped worldwide genomic variation. Here we investigate the interaction between genetic variation and sun-exposure, and how this impacts gene expression regulation. Using RNA-Seq data from 607 human skin samples, we identified thousands of transcripts that are differentially expressed between sun-exposed skin and non-sun-exposed skin. We then tested whether genetic variants may influence each individual’s gene expression response to sun-exposure. Our analysis revealed 10 sun-exposure-dependent gene expression quantitative trait loci (se-eQTLs), including genes involved in skin pigmentation (SLC45A2) and epidermal differentiation (RASSF9). The allele frequencies of the RASSF9 se-eQTL across diverse populations correlate with the magnitude of solar radiation experienced by these populations, suggesting local adaptation to varying levels of sunlight. These results provide the first examples of sun-exposure-dependent regulatory variation and suggest that this variation has contributed to recent human adaptation. Varying levels of sun-exposure across the world have significantly shaped human evolution. Previous analyses have found several skin pigmentation genes with evidence of strong evolutionary pressures throughout human history, manifesting as large differences in the frequency of genomic variants across populations. But even within populations, individuals respond differently to sun-exposure, suggesting variation in addition to the major differences in skin pigmentation across populations. Here we investigated whether genetic variants associate with response to sun-exposure within Europeans. To measure the response we analyzed gene expression in sun-exposed and non-sun-exposed skin, and identified ten genetic variants that associated with the sun-exposure response of nearby genes. One of these genetic variants, which associated with the sun-exposure response of the gene RASSF9, showed evidence of adaptation in humans in response to solar radiation. Together this evidence suggests that the regulation of gene expression is influenced by sun-exposure and that the sun-exposure dependent effect on RASSF9 expression may have had an effect on human fitness. To our knowledge, this is the first example of an environment-dependent regulatory variant with evidence of adaptation in humans.
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影响因子：
12.3
作者：
Castel SE;Levy-Moonshine A;Mohammadi P;Banks E;Lappalainen T
通讯作者：
Lappalainen T
遗传和表观遗传变异对基因调节和剪接的组织特异性作用。
影响因子：
4.5
作者：
Gutierrez-Arcelus M;Ongen H;Lappalainen T;Montgomery SB;Buil A;Yurovsky A;Bryois J;Padioleau I;Romano L;Planchon A;Falconnet E;Bielser D;Gagnebin M;Giger T;Borel C;Letourneau A;Makrythanasis P;Guipponi M;Gehrig C;Antonarakis SE;Dermitzakis ET
通讯作者：
Dermitzakis ET
影响因子：
4.5
作者：
Blair LM;Granka JM;Feldman MW
通讯作者：
Feldman MW
影响因子：
3.3
作者：
Coop, Graham;Witonsky, David;Pritchard, Jonathan K.
通讯作者：
Pritchard, Jonathan K.
DOI：
10.1073/pnas.1115761109
发表时间：
2012-01-24
影响因子：
11.1
作者：
Barreiro, Luis B.;Tailleux, Ludovic;Gilad, Yoav
通讯作者：
Gilad, Yoav