Sex-specific quantitative trait loci affecting longevity in Drosophila melanogaster
Sex-specific quantitative trait loci affecting longevity in Drosophila melanogaster
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DOI：
10.1073/pnas.94.18.9734
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发表时间：
1997-09-02
影响因子：
11.1
通讯作者：
Mackay, TFC
中科院分区：
文献类型：
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作者：
Nuzhdin, SV;Pasyukova, EG;Mackay, TFC
衰老，即随着年龄的增长生存率和生育力的下降，是生物体的一种几乎普遍的特性，衰老和有限的寿命被认为是因为生命后期的弱自然选择允许具有有害的晚期效应的突变的积累，这些效应要么是中性的，（突变累积假说）或有益（拮抗多效性假说），果蝇自发突变的分析，分离变异和协变的模式，选择的晚熟生育的品系在衰老的进化中暗示了这两类突变，但它们的相对贡献和导致自然衰老的单个基因座的特性都不清楚。为了开始剖析寿命数量变异的多重遗传原因，我们利用密集分子标记图对一组重组自交系中影响寿命的数量性状位点（QTL）进行了全基因组筛选。通过复合区间作图和序贯多标记分析，这些QTL对寿命具有较大的性别特异性效应，对存活率和死亡率具有较大的年龄特异性效应，与育性、细胞衰老、抗逆性和雄性特异性效应的候选基因定位在同一区域，晚年龄发病的QTL效应与衰老进化的突变积累假说一致，性别特异性QTL效应表明了一种维持遗传变异的新机制。
Senescence, the decline in survivorship and fertility with increasing age, is a near-universal property of organisms, Senescence and limited lifespan are thought to arise because weak natural selection late in life allows the accumulation of mutations with deleterious late-age effects that are either neutral (the mutation accumulation hypothesis) or beneficial (the antagonistic pleiotropy hypothesis) early in life, Analyses of Drosophila spontaneous mutations, patterns of segregating variation and covariation, and lines selected for late age fertility have implicated both classes of mutation in the evolution of aging, but neither their relative contributions nor the properties of individual loci that cause aging in nature are known. To begin to dissect the multiple genetic causes of quantitative variation in lifespan, we have conducted a genome-wide screen for quantitative trait loci (QTLs) affecting lifespan that segregate among a panel of recombinant inbred lines using a dense molecular marker map, Five autosomal QTLs were mapped by composite interval mapping and by sequential multiple marker analysis, The QTLs had large sex-specific effects on lifespan and age-specific effects on survivorship and mortality and mapped to the same regions as candidate genes with fertility, cellular aging, stress resistance and male-specific effects, Late age-of-onset QTL effects are consistent with the mutation accumulation hypothesis for the evolution of senescence, and sex-specific QTL effects suggest a novel mechanism for maintaining genetic variation for lifespan.