Antagonistic pleiotropy and genetic polymorphism: a perspective

Hedrick, Philip W.

doi:10.1038/sj.hdy.6884400

Cited by 88 publications

(109 citation statements)

References 30 publications

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“…AP could have caused some of the increase in the additive component. Also, AP can lead to senescence even if pleiotropic genes contribute very little genetic variation, because selection can cause near fixation of alleles with beneficial early and deleterious late effects and near elimination of alleles with the reverse pattern of action (41,42). Indeed, many of the recently discovered ''aging'' genes in Drosophila and other model organisms may fall into this category (43)(44)(45)(46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

A test of evolutionary theories of aging

Hughes

Alipaz

Drnevich

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

131

114

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Senescence is a nearly universal feature of multicellular organisms, and understanding why it occurs is a long-standing problem in biology. The two leading theories posit that aging is due to (i) pleiotropic genes with beneficial early-life effects but deleterious late-life effects (''antagonistic pleiotropy'') or (ii) mutations with purely deleterious late-life effects (''mutation accumulation''). Previous attempts to distinguish these theories have been inconclusive because of a lack of unambiguous, contrasting predictions. We conducted experiments with Drosophila based on recent population-genetic models that yield contrasting predictions. Genetic variation and inbreeding effects increased dramatically with age, as predicted by the mutation theory. This increase occurs because genes with deleterious effects with a late age of onset are unopposed by natural selection. Our findings provide the strongest support yet for the mutation theory.S enescence is the decline in organismal fitness and performance with age, and it is a nearly universal feature of multicellular organisms (1-5). Two evolutionary models predict that senescence will evolve because, with few exceptions, the force of natural selection declines with adult age (6). Both theories require the existence of genes with age-specific effects, but the kind of age-specific gene action that is required differs (6). According to the antagonistic pleiotropy (AP) theory, pleiotropic alleles that increase survival or reproduction early in life but decrease survival or reproduction late in life can accumulate in populations, because the selective advantage of the early benefits outweighs the late-life disadvantage. Under the mutation accumulation (MA) theory, alleles with purely detrimental effects can also accumulate if those effects are confined to late life when selection against them is weak. Thus under both theories, populations harbor alleles that are deleterious in old but not in young individuals.Ramifications of the two theories are quite different. Under AP, senescence is due to a ''tradeoff'' between early-and late-life fitness, and any genetic or evolutionary change in senescence will be accompanied by changes in early-life fitness components. In contrast, the MA theory suggests that senescence is caused, at least in part, by alleles that are neutral early in life, and thus genetic or evolutionary changes in senescence need not be accompanied by any change in early-life fitness. In principle, senescence could be slowed or delayed by artificially selecting on late-life fitness or by genetic manipulation of late-acting deleterious alleles, and there would be no cost incurred at earlier ages.These two theories have been subjected to several experimental tests, but previous attempts to distinguish between them have been inconclusive because of a lack of clear and contrasting predictions (4, 7-9). Of the two, AP has received the strongest support, with studies consistently showing negative genetic correlations between early-and late-life fitness, which is...

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Section: Discussionmentioning

confidence: 99%

A test of evolutionary theories of aging

Hughes

Alipaz

Drnevich

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

131

114

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“…The idea that polymorphism may be maintained by antagonistic pleiotropy (when mutations with deleterious effects on some characters have beneficial effects on other characters) (Rose, 1982) is popular and appealing, even though, initially Rose (1982) and more recently Curtsinger et al (1994) and Hedrick (1999) have shown that conditions for polymorphism at pleiotropic loci with antagonistic effects on fitness are rather restrictive. Therefore, even if trade-offs in fitness components have been reported to occur in nature (e.g.…”

Section: Introductionmentioning

confidence: 99%

Antagonistic pleiotropy may help population-level selection in maintaining genetic polymorphism for transmission rate in a model phytopathogenic fungus

2006

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It has been shown theoretically that the conditions for the maintenance of polymorphism at pleiotropic loci with antagonistic effects on fitness components are rather restrictive. Here, we use a metapopulation model to investigate whether antagonistic pleiotropy could help maintain polymorphism involving common deleterious alleles in the phytopathogenic fungus Microbotryum violaceum. This fungus causes anther smut disease of the Caryophyllaceae. A previous model has shown that the sex-linked deleterious alleles can be maintained under a metapopulation structure, when intra-tetrad selfing (mating between products of the same meiosis) is high, due to founder effects and selection at the population level. Here, we add two types of pleiotropic advantages to the metapopulation model. A competitive advantage for strains carrying the sex-linked deleterious alleles did not facilitate their maintenance because competitive situations were too rare. In contrast, higher spore production did facilitate the maintenance of the deleterious alleles at low intra-tetrad mating rates and with a large advantage for spore production. These results show that antagonistic pleiotropy may promote the persistence of genetic variation, in combination with other selective forces. Heredity (2007) 98, 45-52.

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“…Trait-specific dominance has been studied previously in models for the maintenance of genetic variation by pleiotropic antagonistic effects of an allele on two fitness components (Rose 1982;Curtsinger et al 1994;Hedrick 1999). These models, with additive effects of fitness components, can be easily generalized to an arbitrary number of fitness components or phenotypic traits and to arbitrary patterns of pleiotropic effects.…”

Section: Antagonistic Pleiotropy and Trait-specific Dominancementioning

confidence: 99%

“…Models that have considered trait-specific dominance and dominance reversals focus on antagonistic pleiotropy between two fitness components (Rose 1982;Curtsinger et al 1994;Hedrick 1999). Although these models were constructed to investigate the contribution of pleiotropy to the maintenance of genetic variation, they showed that trait-specific dominance facilitates the maintenance of genetic variation by antagonistic pleiotropy.…”

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confidence: 99%

“…Additivity may not always be a reasonable assumption, for example, when mutation is driving the evolutionary process and mutational trait substitutions are intermediate in size. When nonadditivity is considered, degrees of dominance are usually assumed to be parallel in pleiotropic traits affected by the same locus (Hedrick 1999), but that conclusion is mostly based on modeling enzymatic pathways (Keightley and Kacser 1987;Curtsinger et al 1994). It has been shown that degrees of dominance differ between quantitative trait loci for sensory bristle number in Drosophila (Dilda and Mackay 2002) and among morphological traits in the mouse mandible (Ehrich et al 2003).…”

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confidence: 99%

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Protected Polymorphism and Evolutionary Stability in Pleiotropic Models With Trait-Specific Dominance

Dooren¹

2006

Evolution

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Abstract. When alleles have pleiotropic effects on a number of quantitative traits, the degree of dominance between a pair of alleles can be different for each trait. Such trait-specific dominance has been studied previously in models for the maintenance of genetic variation by antagonistic effects of an allele on two fitness components. By generalizing these models to an arbitrary number of fitness components or other phenotypic traits with different degrees of dominance, I show that genetic polymorphism is generally impossible without antagonistic fitness effects of different traits and without trait-specific dominance. I also investigate dominance and pleiotropy from a more long-term evolutionary perspective, allowing for the study of general ecological scenarios, and I discuss the effects of trait-specific dominance on evolutionary stability criteria. When selection is mainly directional and only trait-specific dominance and antagonism cause the emergence of polymorphism, then these polymorphisms can be overtaken by single mutants again, such that they are probably short-lived on an evolutionary time scale. Near evolutionarily singular points where directional selection is absent, trait-specific dominance and overdominance facilitate the emergence of polymorphism and cause evolutionary divergence in some cases. An important outcome of these models is that trait-specific dominance allows for the emergence of genetic polymorphisms without a selective disadvantage for heterozygotes. This removes the scope for the evolution of assortative mate choice and affects dominance modification. Sympatric speciation by disruptive ecological selection requires this heterozygote disadvantage in order to evolve, and therefore it becomes less plausible if the emergence of genetic polymorphism usually occurs via trait-specific dominance and antagonistic effects.

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Antagonistic pleiotropy and genetic polymorphism: a perspective

Cited by 88 publications

References 30 publications

A test of evolutionary theories of aging

A test of evolutionary theories of aging

Antagonistic pleiotropy may help population-level selection in maintaining genetic polymorphism for transmission rate in a model phytopathogenic fungus

Protected Polymorphism and Evolutionary Stability in Pleiotropic Models With Trait-Specific Dominance

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