Deleterious mutations show increasing negative effects with age in Drosophila melanogaster
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RESEARCH ARTICLE
Open Access
Deleterious mutations show increasing negative effects with age in Drosophila melanogaster Martin I. Brengdahl, Christopher M. Kimber, Phoebe Elias, Josephine Thompson and Urban Friberg*
Abstract Background: In order for aging to evolve in response to a declining strength of selection with age, a genetic architecture that allows for mutations with age-specific effects on organismal performance is required. Our understanding of how selective effects of individual mutations are distributed across ages is however poor. Established evolutionary theories assume that mutations causing aging have negative late-life effects, coupled to either positive or neutral effects early in life. New theory now suggests evolution of aging may also result from deleterious mutations with increasing negative effects with age, a possibility that has not yet been empirically explored. Results: To directly test how the effects of deleterious mutations are distributed across ages, we separately measure age-specific effects on fecundity for each of 20 mutations in Drosophila melanogaster. We find that deleterious mutations in general have a negative effect that increases with age and that the rate of increase depends on how deleterious a mutation is early in life. Conclusions: Our findings suggest that aging does not exclusively depend on genetic variants assumed by the established evolutionary theories of aging. Instead, aging can result from deleterious mutations with negative effects that amplify with age. If increasing negative effect with age is a general property of deleterious mutations, the proportion of mutations with the capacity to contribute towards aging may be considerably larger than previously believed. Keywords: Aging, Deleterious mutations, Drosophila melanogaster
Background Aging is the decline in physiological function with age, which results in a gradual decrease in survival and/or reproductive performance [1–4]. Aging affects many organisms and studies have shown that it has a genetic basis (reviewed in [5]). Theory suggests that aging evolves because the strength of selection declines with age [6–11], in combination with mutations with agespecific effects on performance. Two main evolutionary/ genetic theories of aging have been proposed based on * Correspondence: [email protected] IFM Biology, Linköping University, Linköping, Sweden
this idea. They both suggest that aging results from mutations with late acting deleterious effects, while they differ in that Mutation Accumulation (MA; [8]) assumes aging mutations to be neutral early in life whereas antagonistic pleiotropy (AP; [9]) assumes them to be beneficial. The AP and MA theories of aging have both been tested extensively, and evidence in favor of each has been found in the laboratory as well as in the wild (AP, e.g., [12–18], MA, e.g., [19–29]). The two theories make contrasting predictions about how early and late life performances are associated with one another. While AP predicts a negative association, the initial formulati
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