Schmidt P S, Duvernell D D, Eanes W F
Department of Ecology and Evolution, State University of New York at Stony Brook, Stony Brook, NY 11794-5245, USA.
Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10861-5. doi: 10.1073/pnas.190338897.
Examination of the phenotypic effects of specific mutations has been extensively used to identify candidate genes affecting traits of interest. However, such analyses do not reveal anything about the evolutionary forces acting at these loci, or whether standing allelic variation contributes to phenotypic variance in natural populations. The Drosophila gene methuselah (mth) has been proposed as having major effects on organismal stress response and longevity phenotype. Here, we examine patterns of polymorphism and divergence at mth in population level samples of Drosophila melanogaster, D. simulans, and D. yakuba. Mth has experienced an unusually high level of adaptive amino acid divergence concentrated in the intra- and extracellular loop domains of the receptor protein, suggesting the historical action of positive selection on those regions of the molecule that modulate signal transduction. Further analysis of single nucleotide polymorphisms (SNPs) in D. melanogaster provided evidence for contemporary and spatially variable selection at the mth locus. In ten surveyed populations, the most common mth haplotype exhibited a 40% cline in frequency that coincided with population level differences in multiple life-history traits including lifespan. This clinal pattern was not associated with any particular SNP in the coding region, indicating that selection is operating at a closely linked site that may be involved in gene expression. Together, these consistently nonneutral patterns of inter- and intraspecific variation suggest adaptive evolution of a signal transduction pathway that may modulate lifespan in nature.
对特定突变的表型效应进行检测已被广泛用于鉴定影响目标性状的候选基因。然而，此类分析并未揭示作用于这些基因座的进化力量，也未揭示现存等位基因变异是否对自然种群的表型变异有贡献。果蝇基因玛士撒拉（mth）被认为对生物体应激反应和寿命表型有重大影响。在此，我们检测了黑腹果蝇、拟暗果蝇和雅库布果蝇种群水平样本中mth基因的多态性和分化模式。Mth经历了异常高水平的适应性氨基酸分化，集中在受体蛋白的细胞内和细胞外环结构域，这表明在调节信号转导的分子区域上存在正选择的历史作用。对黑腹果蝇单核苷酸多态性（SNP）的进一步分析为mth基因座当代和空间可变选择提供了证据。在十个被调查的种群中，最常见的mth单倍型频率呈现出40%的渐变，这与包括寿命在内的多个生活史性状的种群水平差异相吻合。这种渐变模式与编码区的任何特定SNP均无关联，表明选择作用于一个可能参与基因表达的紧密连锁位点。总之，这些种间和种内变异的一致非中性模式表明，一条可能在自然环境中调节寿命的信号转导途径发生了适应性进化。
