影响果蝇寿命自然变异的数量性状基因座。

Quantitative trait loci affecting natural variation in Drosophila longevity.

作者信息

Geiger-Thornsberry Gretchen L, Mackay Trudy F C

机构信息

Department of Genetics, Box 7614, North Carolina State University, Raleigh 27695, USA.

出版信息

Mech Ageing Dev. 2004 Mar;125(3):179-89. doi: 10.1016/j.mad.2003.12.008.

DOI:10.1016/j.mad.2003.12.008

PMID:15013662

Abstract

Limited life span and senescence are universal phenomena, controlled by genetic and environmental factors whose interactions both limit life span and generate variation in life span between individuals, populations and species. To understand the genetic architecture of longevity it is necessary to know what loci affect variation in life span, what are the allelic effects at these loci and what molecular polymorphisms define quantitative trait locus (QTL) alleles. Here, we used quantitative complementation tests to determine whether genes that regulate longevity also contribute to naturally occurring variation in Drosophila life span. Inbred strains derived from a natural population were crossed to stocks containing null mutations (m) or deficiencies (Df) uncovering the candidate genes, maintained over a Balancer (Bal) chromosome. We measured the life span of the resulting F(1) genotypes, +(i)/m (Df) and +(i)/Bal, where +(i) denotes one of the i natural alleles. Failure of the QTL alleles to complement the candidate gene mutation is indicated by a significant cross (mutant versus wild-type allele of the candidate gene) by inbred line interaction term from analysis of variance of life span. Failure to complement indicates a genetic interaction between the candidate gene allele and the naturally occurring life span QTL, and implicates the candidate gene as potential cause of variation in longevity. Of the 16 candidate regions and genes tested, Df(2L)c17, Df(3L)Ly, Df(3L)AC1 and Df(3R)e-BS2 showed significant failure to complement wild-type alleles in both sexes, and an Alcohol dehydrogenase mutant failed to complement in females. Several genes that regulate life span (e.g., Superoxide dismutase, Catalase, and rosy) complemented the life span effects of wild-derived alleles, suggesting little natural variation affecting longevity at these loci, at least in this sample of alleles. Quantitative complementation tests are therefore useful for identifying QTL contributing to segregating genetic variation in life span in nature.

摘要

有限的寿命和衰老都是普遍现象，受遗传和环境因素控制，这些因素的相互作用既限制了寿命，又导致个体、种群和物种之间寿命产生差异。要了解长寿的遗传结构，有必要知道哪些基因座影响寿命差异，这些基因座的等位基因效应是什么，以及哪些分子多态性定义了数量性状基因座（QTL）等位基因。在这里，我们使用定量互补试验来确定调控寿命的基因是否也对果蝇寿命的自然变异有贡献。将来自自然种群的近交系与含有无效突变（m）或缺失（Df）的品系杂交，这些突变或缺失揭示了候选基因，并通过平衡染色体维持。我们测量了所得F(1)基因型 +(i)/m (Df) 和 +(i)/Bal 的寿命，其中 +(i) 表示i个自然等位基因之一。寿命方差分析中，近交系交互项的显著交叉（候选基因的突变体与野生型等位基因）表明QTL等位基因未能补充候选基因突变。未能补充表明候选基因等位基因与自然发生的寿命QTL之间存在遗传相互作用，并暗示该候选基因是寿命变异的潜在原因。在测试的16个候选区域和基因中，Df(2L)c17、Df(3L)Ly、Df(3L)AC1和Df(3R)e-BS2在两性中均显著未能补充野生型等位基因，并且一个乙醇脱氢酶突变体在雌性中未能补充。几个调控寿命的基因（如超氧化物歧化酶、过氧化氢酶和玫瑰色）补充了野生来源等位基因的寿命效应，这表明至少在这个等位基因样本中，这些基因座上影响长寿的自然变异很小。因此，定量互补试验有助于识别导致自然界寿命遗传变异分离的QTL。