Understanding the genetic basis of variation in life span is a major challenge that is difficult to address in human populations. Evolutionary theory predicts that alleles affecting natural variation in life span will have properties that enable them to persist in populations at intermediate frequencies, such as late-life–specific deleterious effects, antagonistic pleiotropic effects on early and late-age fitness components, and/or sex- and environment-specific or antagonistic effects. Here, we quantified variation in life span in males and females reared in 3 thermal environments for the sequenced, inbred lines of the Drosophila melanogaster Genetic Reference Panel (DGRP) and an advanced intercross outbred population derived from a subset of DGRP lines. Quantitative genetic analyses of life span and the micro-environmental variance of life span in the DGRP revealed significant genetic variance for both traits within each sex and environment, as well as significant genotype-by-sex interaction (GSI) and genotype-by-environment interaction (GEI). Genome-wide association (GWA) mapping in both populations implicates over 2,000 candidate genes with sex- and environment-specific or antagonistic pleiotropic allelic effects. Over 1,000 of these genes are associated with variation in life span in other D. melanogaster populations. We functionally assessed the effects of 15 candidate genes using RNA interference (RNAi): all affected life span and/or micro-environmental variance of life span in at least one sex and environment and exhibited sex-and environment-specific effects. Our results implicate novel candidate genes affecting life span and suggest that variation for life span may be maintained by variable allelic effects in heterogeneous environments.

了解寿命变异的遗传基础是一项难以在人群中解决的重大挑战。进化理论预测，影响寿命自然变异的等位基因将具有使它们能够以中等频率在种群中持续存在的特性，例如晚年特定的有害影响、对早年和晚年健康成分的拮抗多效性影响，和/或性别和环境特异性或拮抗作用。在这里，我们量化了在 3 个热环境中饲养的雄性和雌性黑腹果蝇的测序近交系的寿命变化遗传参考面板 (DGRP) 和源自 DGRP 品系子集的高级互交远交种群。DGRP中寿命的定量遗传分析和寿命的微环境变异揭示了每个性别和环境中两个性状的显着遗传变异，以及显着的基因型-性别相互作用（GSI）和基因型-环境互动（GEI）。两个群体中的全基因组关联 (GWA) 映射涉及 2,000 多个具有性别和环境特异性或拮抗性多效等位基因效应的候选基因。这些基因中有 1,000 多个与其他D 的寿命变化有关。黑腹人口。我们使用 RNA 干扰 (RNAi) 从功能上评估了 15 个候选基因的影响：在至少一种性别和环境中，所有受影响的寿命和/或寿命的微环境变化，并表现出性别和环境特异性影响。我们的结果暗示了影响寿命的新候选基因，并表明寿命的变化可能通过异质环境中的可变等位基因效应来维持。