Department of Molecular and Computation Biology, University of Southern California, Los Angeles, CA, USA.
Heredity (Edinb). 2012 Oct;109(4):226-34. doi: 10.1038/hdy.2012.34. Epub 2012 Jul 4.
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 Yolk protein 1-3 (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.
生物学中一个长期存在的问题是理解遗传变异如何导致表型变异。已经报道了许多层次的关联,但因果推断仍然难以捉摸。我们建议依赖分子生物学方法所建立的因果关系知识。现有的分子知识形成了一个坚实的基础,在此基础上可以构建连接遗传变异、转录变异和表型变异的假设。性别决定途径是一个成熟的分子网络,Yolk 蛋白 1-3(Yp)基因是最下游的靶标。我们的分析表明,已知在途径中上游的基因表达的遗传变异解释了下游靶标的变异。两性之间的关系不同,每个 Yp 都有独特的转录模式。Yp 的表达与寿命呈显著负相关,寿命是一个重要的生活史特征,对雄性和雌性都是如此。