Genetic basis of transcriptome diversity in Drosophila melanogaster
Genetic basis of transcriptome diversity in Drosophila melanogaster
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DOI：
10.1073/pnas.1519159112
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发表时间：
2015-11-03
影响因子：
11.1
通讯作者：
Mackay, Trudy F. C.
中科院分区：
文献类型：
--
作者：
Huang, Wen;Carbone, Mary Anna;Mackay, Trudy F. C.
了解 DNA 序列变异如何转化为复杂表型的变异仍然难以捉摸，但对于预测适应性进化、选择农业上重要的动物和作物以及个性化医疗至关重要。基因表达可以提供 DNA 序列变异和生物体表型之间的联系，并且可以有效、准确地测量其丰度。在这里，我们量化了果蝇遗传参考面板 (DGRP) 测序自交系中基因表达的全基因组变异，将注释的果蝇转录组增加了 11%，包括数千个新转录区域 (NTR)。我们发现，42% 的果蝇转录组在雄性和雌性中存在遗传变异，包括 NTR，并且被组织成遗传相关转录本的模块。我们发现 NTR 通常与蛋白质编码基因的表达呈负相关，我们利用这些基因对 NTR 进行功能注释。我们确定了基因表达均值和方差的调控变异，这些变异在很大程度上具有独立的遗传控制。基因表达平均值（而非方差）的表达数量性状基因座（eQTL）集中在基因附近。值得注意的是，变异 eQTL 经常与这些基因中的局部变异相互作用以调节基因表达。这种对群体规模转录组多样性及其在 DGRP 中的遗传基础的全面表征对于系统理解数量性状变异至关重要。
Understanding how DNA sequence variation is translated into variation for complex phenotypes has remained elusive but is essential for predicting adaptive evolution, for selecting agriculturally important animals and crops, and for personalized medicine. Gene expression may provide a link between variation in DNA sequence and organismal phenotypes, and its abundance can be measured efficiently and accurately. Here we quantified genome-wide variation in gene expression in the sequenced inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP), increasing the annotated Drosophila transcriptome by 11%, including thousands of novel transcribed regions (NTRs). We found that 42% of the Drosophila transcriptome is genetically variable in males and females, including the NTRs, and is organized into modules of genetically correlated transcripts. We found that NTRs often were negatively correlated with the expression of protein-coding genes, which we exploited to annotate NTRs functionally. We identified regulatory variants for the mean and variance of gene expression, which have largely independent genetic control. Expression quantitative trait loci (eQTLs) for the mean, but not for the variance, of gene expression were concentrated near genes. Notably, the variance eQTLs often interacted epistatically with local variants in these genes to regulate gene expression. This comprehensive characterization of population-scale diversity of transcriptomes and its genetic basis in the DGRP is critically important for a systems understanding of quantitative trait variation.