Diverse environmental perturbations reveal the evolution and context-dependency of genetic effects on gene expression levels.
Diverse environmental perturbations reveal the evolution and context-dependency of genetic effects on gene expression levels.
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DOI：
10.1101/gr.276430.121
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发表时间：
2022-10
期刊：
影响因子：
7
通讯作者：
Ayroles, Julien F.
中科院分区：
文献类型：
--
作者：
Lea, Amanda J.;Peng, Julie;Ayroles, Julien F.
越来越多的人认识到，除了由个人的基因和环境决定外，大多数复杂的特征也是由这两个因素之间鲜为人知的相互作用决定的。所谓的“基因型×环境”(G×E)相互作用在生物体水平上仍然很难定位，但可以用分子表型来揭示。为了大规模地实现这一点，我们使用TM3的SEQ对来自1000基因组计划的544个永生化B细胞系的12种细胞环境中的转录进行了分析。我们绘制了不同环境中基因表达水平的遗传基础图，并揭示了一个上下文相关的遗传结构：与对照条件相比，处理组基因表达水平的平均遗传力增加，平均而言，每个处理在11%的基因上显示了新的表达数量性状基因座(EQTL)。在我们的实验中，所有已识别的eQTL中有22%是上下文相关的，这组人的性状和疾病相关基因丰富。此外，进化分析表明，正向选择形成了G×E基因座，这些基因座参与了对免疫挑战和激素的反应，但对人造化学物质没有反应。我们假设，这反映了选择作用于对最近引入人类环境的分子的反应的机会减少。总之，我们的工作强调了在研究和解释G×E相互作用时考虑暴露的进化史的重要性，并为人类群体中维持G×E基因座的进化机制提供了新的见解。
There is increasing appreciation that, in addition to being shaped by an individual's genotype and environment, most complex traits are also determined by poorly understood interactions between these two factors. So-called “genotype × environment” (G×E) interactions remain difficult to map at the organismal level but can be uncovered using molecular phenotypes. To do so at large scale, we used TM3′seq to profile transcriptomes across 12 cellular environments in 544 immortalized B cell lines from the 1000 Genomes Project. We mapped the genetic basis of gene expression levels across environments and revealed a context-dependent genetic architecture: The average heritability of gene expression levels increased in treatment relative to control conditions, and on average, each treatment revealed new expression quantitative trait loci (eQTLs) at 11% of genes. Across our experiments, 22% of all identified eQTLs were context-dependent, and this group was enriched for trait- and disease-associated loci. Further, evolutionary analyses suggested that positive selection has shaped G×E loci involved in responding to immune challenges and hormones but not to man-made chemicals. We hypothesize that this reflects a reduced opportunity for selection to act on responses to molecules recently introduced into human environments. Together, our work highlights the importance of considering an exposure's evolutionary history when studying and interpreting G×E interactions, and provides new insight into the evolutionary mechanisms that maintain G×E loci in human populations.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
9.8
作者：
Dahl, Andy;Khiem Nguyen;Zaitlen, Noah
通讯作者：
Zaitlen, Noah
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