MUTATION, PLEIOTROPY AND THE GENETIC STRUCTURE OF AGING

这项研究将提供关于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的进化理论都至关重要，但知之甚少。这项研究将明确确定特定年龄的突变率，以及它们在不同年龄段是否恒定。它还将确定年龄特异性突变效应的大小，以及这些效应是否恒定和/或与年龄相关。 这将通过实验操作基因型来完成，以积累自发突变。该研究还将确定基因型之间的遗传方差分量是否随着年龄的增长而增加，正如衰老的突变累积理论所预测的那样，检查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），明确联系的发展速度和衰老速度，预测衰老的拮抗多效性理论。这将通过共定位青少年发育速率和衰老的QTL来完成，以鉴定影响这两个过程的基因座。对年龄特异性突变的深刻理解提供了一个透镜，使未来的研究集中在衰老及其与发育的潜在联系上。

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.