MUTATION, PLEIOTROPY AND THE GENETIC STRUCTURE OF AGING

这项研究将提供有关具有特定年龄效应的突变性质的基本信息。年龄相关突变的特性是所有衰老进化理论的关键，但人们知之甚少。这项研究将明确确定特定年龄的变异率，以及它们是否在不同年龄保持不变。它还将确定特定年龄突变效应的大小，以及这些影响是否在不同年龄之间是恒定的和/或相关的。这将通过实验操纵的基因类型来积累自发突变。这项研究还将确定基因类型之间的遗传差异成分是否会像衰老的突变累积理论所预测的那样随着年龄的增长而增加，并检查自然发生的基因类型的特定年龄段的存活率和繁殖力。这项研究的最后一个组成部分将确定数量性状基因座(QTL)，这些基因座明确地将发育速度和衰老速度联系在一起，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体发育速度和衰老的QTL来完成，以确定影响这两个过程的基因座。对特定年龄突变的深入了解为未来研究衰老及其与发育的潜在联系提供了一个镜头。

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.