pubmed.ncbi.nlm.nih.gov

Heterozygote Advantage Is a Common Outcome of Adaptation in Saccharomyces cerevisiae - PubMed

Heterozygote Advantage Is a Common Outcome of Adaptation in Saccharomyces cerevisiae

Diamantis Sellis et al. Genetics. 2016 Jul.

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.

Copyright © 2016 by the Genetics Society of America.

PubMed Disclaimer

Figures

Figure 1
Figure 1

In the sequenced lineages the first adaptive mutations appeared multiple times. The first adaptive mutation in each clone is the expansion of genes HXT6 and HXT7 (HXT6/7 CNV), the partial duplication of chromosome IV (chrIV CNV), and the chromosome XV partial duplication and haploidization (chrXV CNV). The shaded clones have the wild-type colony phenotype.

Figure 2
Figure 2

Heterozygote advantage in the expansion of the HXT6/7 CNV. Relative fitness from pairwise competitions against a common reference strain. The heterozygote HXT6/7 clone was significantly more fit than both the homozygote HXT6/7 (P-value = 0.0173, one-tailed, paired t-test, indicated by *) and the ancestral homozygote (P-value = 0.0015, indicated by **).

Figure 3
Figure 3

Simplified diagram of glucose sensing and transport pathways annotated to show the major adaptive strategies to growth in a glucose-limited environment [adapted from Kaniak et al. (2004)]. Adaptation in haploids (blue) includes loss of function mutations in the sensing pathway or expansion of the copy number of glucose transporters (Kvitek and Sherlock 2013). Evolved diploid clones (red) had (1) a haploidization of STD1; (2) a duplication of MTH1, HXT3, HXT6, and HXT7; or (3) an expansion of HXT6 and HXT7.

Similar articles

Cited by

References

    1. Anderson J. B., Sirjusingh C., Ricker N., 2004. Haploidy, diploidy and evolution of antifungal drug resistance in Saccharomyces cerevisiae. Genetics 168: 1915–1923. - PMC - PubMed
    1. Ashburner M., Ball C. A., Blake J. A., Botstein D., Butler H., et al. , 2000. Gene ontology: tool for the unification of biology. Nat. Genet. 25: 25–29. - PMC - PubMed
    1. Assaf Z. J., Petrov D. A., Blundell J. R., 2015. Obstruction of adaptation in diploids by recessive, strongly deleterious alleles. Proc. Natl. Acad. Sci. USA 112: E2658-66. - PMC - PubMed
    1. Bevis B. J., Glick B. S., 2002. Rapidly maturing variants of the Discosoma red fluorescent protein (DsRed). Nat. Biotechnol. 20: 83–87. - PubMed
    1. Brown C. J. C., Todd K. M., Rosenzweig R. F. R., 1998. Multiple duplications of yeast hexose transport genes in response to selection in a glucose-limited environment. Mol. Biol. Evol. 15: 931–942. - PubMed

MeSH terms