MUTATION, PLEIOTROPY AND THE GENETIC STRUCTURE OF AGING

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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.