MUTATION, PLEIOTROPY AND THE GENETIC STRUCTURE OF AGING

这项研究将提供有关具有年龄特异性影响的突变性质的基本信息。年龄特异性突变的特性对所有衰老进化理论都至关重要，但却鲜为人知。这项研究将明确确定年龄特异性突变的比率，以及它们是否在各个年龄段都是恒定的。它还将确定年龄特异性突变效应的大小，以及这些效应在不同年龄之间是否恒定和/或相关。这将通过实验操作基因型来积累自发突变。该研究还将确定基因型之间的遗传变异成分是否随着年龄的增长而增加，正如衰老的突变积累理论所预测的那样，研究自然发生的基因型的年龄特异性生存和繁殖力。研究的最后一个组成部分将确定数量性状位点（QTL）明确连接发育率和衰老率，正如衰老的拮抗多效性理论所预测的那样。这将通过共同定位幼鱼发育速率和衰老的QTL来确定影响这两个过程的位点。对年龄特异性突变的深刻理解为未来研究衰老及其与发育的潜在联系提供了一个视角。

The research will provide fundamental information about the nature of mutations with age- specific effects. Properties of age-specific mutations are critical to all evolutionary theories of senescence, but poorly known. The research will explicitly determine the rates of age-specific mutations and whether they are constant across ages. It will also determine the magnitudes of age-specific mutational effects and whether the effects are constant and/or correlated across ages. This will be done with genotypes experimentally manipulated to accumulate spontaneous mutations. The research will also determine if components of genetic variance among genotypes increase with age, as predicted by the mutation accumulation theory of senescence, examining the age-specific survival and fecundity of naturally-occurring genotypes. The last component of the research will identify quantitative trait loci (QTL) that explicitly link development rates and senescence rates, as predicted by the antagonistic pleiotropy theory of senescence. This will be done by co-mapping QTL for juvenile development rate and senescence to identify loci that affect both processes. A strong understanding of age-specific mutation provides a lens with which to focus future research on senescence and its potential link to development.