Heterozygote advantage as a natural consequence of adaptation in diploids
- 5 December 2011
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (51), 20666-20671
- https://doi.org/10.1073/pnas.1114573108
Abstract
Molecular adaptation is typically assumed to proceed by sequential fixation of beneficial mutations. In diploids, this picture presupposes that for most adaptive mutations, the homozygotes have a higher fitness than the heterozygotes. Here, we show that contrary to this expectation, a substantial proportion of adaptive mutations should display heterozygote advantage. This feature of adaptation in diploids emerges naturally from the primary importance of the fitness of heterozygotes for the invasion of new adaptive mutations. We formalize this result in the framework of Fisher's influential geometric model of adaptation. We find that in diploids, adaptation should often proceed through a succession of short-lived balanced states that maintain substantially higher levels of phenotypic and fitness variation in the population compared with classic adaptive walks. In fast-changing environments, this variation produces a diversity advantage that allows diploids to remain better adapted compared with haploids despite the disadvantage associated with the presence of unfit homozygotes. The short-lived balanced states arising during adaptive walks should be mostly invisible to current scans for long-term balancing selection. Instead, they should leave signatures of incomplete selective sweeps, which do appear to be common in many species. Our results also raise the possibility that balancing selection, as a natural consequence of frequent adaptation, might play a more prominent role among the forces maintaining genetic variation than is commonly recognized.Keywords
This publication has 48 references indexed in Scilit:
- Evidence for Pervasive Adaptive Protein Evolution in Wild MicePLoS Genetics, 2010
- Adaptive Evolution of Pelvic Reduction in Sticklebacks by Recurrent Deletion of a Pitx1 EnhancerScience, 2010
- Targets of Balancing Selection in the Human GenomeMolecular Biology and Evolution, 2009
- Optimization of gene expression by natural selectionProceedings of the National Academy of Sciences of the United States of America, 2009
- Molecular characterization of clonal interference during adaptive evolution in asexual populations of Saccharomyces cerevisiaeNature Genetics, 2008
- High Rate of Recent Transposable Element–Induced Adaptation in Drosophila melanogasterPLoS Biology, 2008
- Identifying footprints of directional and balancing selection in marine and freshwater three‐spined stickleback (Gasterosteus aculeatus) populationsMolecular Ecology, 2008
- A Single IGF1 Allele Is a Major Determinant of Small Size in DogsScience, 2007
- The genetic theory of adaptation: a brief historyNature Reviews Genetics, 2005
- The Genetic Architecture of Parallel Armor Plate Reduction in Threespine SticklebacksPLoS Biology, 2004