Weissman, DanielIST Austria; Feldman, Marcus; Fisher, Daniel
Biological traits result in part from interactions between different genetic loci. This can lead to sign epistasis, in which a beneficial adaptation involves a combination of individually deleterious or neutral mutations; in this case, a population must cross a “fitness valley” to adapt. Recombination can assist this process by combining mutations from different individuals or retard it by breaking up the adaptive combination. Here, we analyze the simplest fitness valley, in which an adaptation requires one mutation at each of two loci to provide a fitness benefit. We present a theoretical analysis of the effect of recombination on the valley-crossing process across the full spectrum of possible parameter regimes. We find that low recombination rates can speed up valley crossing relative to the asexual case, while higher recombination rates slow down valley crossing, with the transition between the two regimes occurring when the recombination rate between the loci is approximately equal to the selective advantage provided by the adaptation. In large populations, if the recombination rate is high and selection against single mutants is substantial, the time to cross the valley grows exponentially with population size, effectively meaning that the population cannot acquire the adaptation. Recombination at the optimal (low) rate can reduce the valley-crossing time by up to several orders of magnitude relative to that in an asexual population.
This work was supported in part by a Robert N. Noyce Stanford Graduate Fellowship and European Research Council grant 250152 (to D.B.W.) and by National Institutes of Health grant GM 28016 (to M.W.F.). We thank Michael Desai for many ideas and discussions and are grateful to Joanna Masel and an anonymous reviewer for their helpful suggestions.
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Weissman D, Feldman M, Fisher D. The rate of fitness-valley crossing in sexual populations. Genetics. 2010;186(4):1389-1410. doi:10.1534/genetics.110.123240
Weissman, D., Feldman, M., & Fisher, D. (2010). The rate of fitness-valley crossing in sexual populations. Genetics. Genetics Society of America. https://doi.org/10.1534/genetics.110.123240
Weissman, Daniel, Marcus Feldman, and Daniel Fisher. “The Rate of Fitness-Valley Crossing in Sexual Populations.” Genetics. Genetics Society of America, 2010. https://doi.org/10.1534/genetics.110.123240.
D. Weissman, M. Feldman, and D. Fisher, “The rate of fitness-valley crossing in sexual populations,” Genetics, vol. 186, no. 4. Genetics Society of America, pp. 1389–1410, 2010.
Weissman D, Feldman M, Fisher D. 2010. The rate of fitness-valley crossing in sexual populations. Genetics. 186(4), 1389–1410.
Weissman, Daniel, et al. “The Rate of Fitness-Valley Crossing in Sexual Populations.” Genetics, vol. 186, no. 4, Genetics Society of America, 2010, pp. 1389–410, doi:10.1534/genetics.110.123240.
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