Data from: Genetic variation in the Yolk protein expression network of Drosophila melanogaster: sex-biased negative correlations with longevity

One of the persistent problems in biology is understanding how genetic variation contributes to phenotypic variation. Associations at many levels have been reported, and yet causal inference has remained elusive. We propose to rely on the knowledge of causal relationships established by molecular biology approaches. The existing molecular knowledge forms a firm backbone upon which hypotheses connecting genetic variation, transcriptional variation and phenotypic variation can be built. The sex determination pathway is a well-established molecular network, with the Yp genes as the most downstream target. Our analyses reveal that genetic variation in expression for genes known to be upstream in the pathway explains variation in downstream targets. Relationships differ between the two sexes, and each Yp has a distinct transcriptional pattern. Yp expression is significantly negatively correlated with longevity, an important life history trait, for both males and females.

解析遗传变异如何驱动表型变异，是生物学领域长期悬而未决的核心难题之一。尽管已有多个层级的关联关系被报道，但因果推断始终难以实现。我们提出可依托分子生物学方法所确立的因果关系知识框架，现有分子生物学知识构成了坚实的理论基础，可在此基础上构建连接遗传变异、转录变异与表型变异的研究假说。性别决定通路是一套成熟完善的分子网络，其中Yp基因（Yp genes）为其最下游的作用靶标。我们的分析结果显示，该通路中已知上游基因的表达遗传变异，能够解释下游靶标的表达变异情况。上述关联关系在雌雄两性间存在显著差异，且每个Yp基因均具有独特的转录表达模式。无论雄性还是雌性个体，Yp基因的表达水平均与寿命这一重要生活史性状呈显著负相关。