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Genetics. 2016 Jul;203(3):1401-13. doi: 10.1534/genetics.115.185165. Epub 2016 May 18.

Heterozygote Advantage Is a Common Outcome of Adaptation in Saccharomyces cerevisiae.

Author information

1
Department of Biology, Stanford University, California 94305 Départment PEGASE, Université Lyon 1, CNRS UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, 69622 Villeurbanne cedex, France, Laboratoire de Biométrie et Biologie Evolutive, Villeurbanne, France sellisd@gmail.com.
2
Department of Genetics, Stanford University, California 94305 Invitae, San Francisco, California 94107.
3
Department of Genetics, Stanford University, California 94305.
4
Department of Biology, Stanford University, California 94305.

Abstract

Adaptation in diploids is predicted to proceed via mutations that are at least partially dominant in fitness. Recently, we argued that many adaptive mutations might also be commonly overdominant in fitness. Natural (directional) selection acting on overdominant mutations should drive them into the population but then, instead of bringing them to fixation, should maintain them as balanced polymorphisms via heterozygote advantage. If true, this would make adaptive evolution in sexual diploids differ drastically from that of haploids. The validity of this prediction has not yet been tested experimentally. Here, we performed four replicate evolutionary experiments with diploid yeast populations (Saccharomyces cerevisiae) growing in glucose-limited continuous cultures. We sequenced 24 evolved clones and identified initial adaptive mutations in all four chemostats. The first adaptive mutations in all four chemostats were three copy number variations, all of which proved to be overdominant in fitness. The fact that fitness overdominant mutations were always the first step in independent adaptive walks supports the prediction that heterozygote advantage can arise as a common outcome of directional selection in diploids and demonstrates that overdominance of de novo adaptive mutations in diploids is not rare.

KEYWORDS:

adaptation; diploid; experimental evolution; heterozygote advantage

PMID:
27194750
PMCID:
PMC4937471
DOI:
10.1534/genetics.115.185165
[Indexed for MEDLINE]
Free PMC Article

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