Quantitative genetics of mutations affecting ageing in Drosophila

BBSRC-funded Studentship

Professor B. Charlesworth

The aim of the project is to investigate the extent to which spontaneous mutations affect age-specific patterns of mortality in Drosophila melanogaster, using the methods of quantitative genetics. Theoretical work has shown that late-acting deleterious mutations accumulate in a population at higher frequencies than early-acting ones, contributing to an overall decline in the mean mortality rate, and an increase in the genetic variance of mortality rate, with increasing age. These predictions have received some support from empirical research in my laboratory, although the importance of mutation accumulation for ageing is still far from clear. A basic premise of the theory is that mutations with age-specific effects on mortality occur at a rate that is high enough to account for senescent increase in mortality. Little evidence on this question is currently available. The project aims to help fill this gap.

In order to detect age-specific mutations, we need (i) methods for measuring mortality rates in large cohorts of individuals of known genotype (ii) genotypes which differ only with respect to newly-arisen mutations. In regard to (i), we have been following cohorts of around 750 virgin flies in plastic cages, and counting deaths over 3-day intervals. This method appears to give reproducible, line-specific, patterns of linear increases in log mortality with age, and hence is suitable for the purpose of looking at genotypic effects on age-specific mortality. Virgin flies are used, in order to avoid confounding effects of reproductive effort on mortality. In regard to (ii), we have been maintaining lines which are accumulating spontaneous mutations, as part of a BBSRC-funded project; these will provide suitable material for detecting mutational effects. The resulting data will be used to search for evidence of mutations with effects confined to specific ranges of ages. The question of whether mutational variance in mortality rates changes with age, raised by some previous results, will be examined. The existence of late-age levelling of mortality rates in virgin flies, a controversial issue in ageing research, will also be tested for.

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