Data from: Contrasting selection pressures on components of the Ras-mediated signal transduction pathway in Drosophila

The molecular genetics of several signal transduction pathways is well characterized, providing an opportunity to address the nature of the population genetic forces acting on functionally related suites of pleiotropic regulatory genes. Signal transduction is the process by which signals are transmitted from the cell surface to the nucleus or other cellular structures. It plays a fundamental role in regulating a wide range of developmental and physiological processes, many of which are likely to be subject to buffering mechanisms. Here we infer that contrasting selection pressures act on six components of the Ras signal transduction pathway by comparing sequences obtained from 25 alleles of Drosophila melanogaster with one allele of the sibling species D. simulans. The three most upstream components of the cascade, Ras, Drk and polehole, experience strong purifying selection, as they show no fixed amino acid differences between the species and just a handful of rare replacement polymorphisms within D. melanogaster. This portion of the pathway is likely to act as a control point in signal transduction, because the more downstream components Dsor1, corkscrew and Ksr, each show several amino acid replacements between the species. Furthermore, Ksr is nearly monomorphic within D. melanogaster, and application of the HKA and McDonald and Kreitman tests indicate that this gene may have experienced a recent selective sweep, suggesting that modifiers of Ras kinase signalling are the most likely source of quantitative variation associated with this core regulatory pathway.

多种信号转导通路（signal transduction pathway）的分子遗传学特征已得到充分阐释，为探究作用于功能相关多效性调控基因组的群体遗传作用力本质提供了契机。信号转导是指信号从细胞表面传递至细胞核或其他细胞结构的过程，其在调控各类发育与生理进程中发挥基础性作用，其中诸多进程大概率受缓冲机制调控。本研究通过比对黑腹果蝇（Drosophila melanogaster）25个等位基因与近缘姊妹种拟果蝇（Drosophila simulans）的1个等位基因序列，推断Ras信号转导通路的6个组分受到相反的选择压力作用。该级联反应的三个最上游组分——Ras、Drk与polehole，经历了强烈的纯化选择（purifying selection）：二者间未检测到固定氨基酸差异，且黑腹果蝇群体内仅存在寥寥数种罕见的置换多态性。这部分通路大概率充当信号转导的调控节点，因为下游的Dsor1、corkscrew与Ksr三个组分，在两物种间均存在多处氨基酸置换。此外，Ksr在黑腹果蝇群体内几乎呈单态性，采用HKA检验（Hudson-Kreitman-Aguade test）与麦克唐纳-克里特曼检验（McDonald and Kreitman tests）进行分析的结果显示，该基因可能经历了近期的选择性清除（selective sweep），这表明Ras激酶信号通路的修饰因子极有可能是与该核心调控通路相关的数量变异的来源。