Polygenic cis-regulatory adaptation in the evolution of yeast pathogenicity

Hunter B. Fraser, Sasha Levy, Arun Chavan, Hiral B. Shah, J. Christian Perez, Yiqi Zhou, Mark Siegal, Himanshu Sinha

Research output: Contribution to journalArticle

Abstract

The acquisition of new genes, via horizontal transfer or gene duplication/diversification, has been the dominant mechanism thus far implicated in the evolution of microbial pathogenicity. In contrast, the role of many other modes of evolution - such as changes in gene expression regulation - remains unknown. A transition to a pathogenic lifestyle has recently taken place in some lineages of the budding yeast Saccharomyces cerevisiae. Here we identify a module of physically interacting proteins involved in endocytosis that has experienced selective sweeps for multiple cis-regulatory mutations that down-regulate gene expression levels in a pathogenic yeast. To test if these adaptations affect virulence, we created a panel of single-allele knockout strains whose hemizygous state mimics the genes' adaptive down-regulations, and measured their virulence in a mammalian host. Despite having no growth advantage in standard laboratory conditions, nearly all of the strains were more virulent than their wild-type progenitor, suggesting that these adaptations likely played a role in the evolution of pathogenicity. Furthermore, genetic variants at these loci were associated with clinical origin across 88 diverse yeast strains, suggesting the adaptations may have contributed to the virulence of a wide range of clinical isolates. We also detected pleiotropic effects of these adaptations on a wide range of morphological traits, which appear to have been mitigated by compensatory mutations at other loci. These results suggest that cis-regulatory adaptation can occur at the level of physically interacting modules and that one such polygenic adaptation led to increased virulence during the evolution of a pathogenic yeast.

Original languageEnglish (US)
Pages (from-to)1930-1939
Number of pages10
JournalGenome Research
Volume22
Issue number10
DOIs
StatePublished - Oct 2012

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Virulence
Yeasts
Down-Regulation
Horizontal Gene Transfer
Mutation
Saccharomycetales
Gene Duplication
Gene Expression Regulation
Endocytosis
Saccharomyces cerevisiae
Life Style
Alleles
Gene Expression
Growth
Genes
Proteins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Fraser, H. B., Levy, S., Chavan, A., Shah, H. B., Perez, J. C., Zhou, Y., ... Sinha, H. (2012). Polygenic cis-regulatory adaptation in the evolution of yeast pathogenicity. Genome Research, 22(10), 1930-1939. https://doi.org/10.1101/gr.134080.111

Polygenic cis-regulatory adaptation in the evolution of yeast pathogenicity. / Fraser, Hunter B.; Levy, Sasha; Chavan, Arun; Shah, Hiral B.; Perez, J. Christian; Zhou, Yiqi; Siegal, Mark; Sinha, Himanshu.

In: Genome Research, Vol. 22, No. 10, 10.2012, p. 1930-1939.

Research output: Contribution to journalArticle

Fraser, HB, Levy, S, Chavan, A, Shah, HB, Perez, JC, Zhou, Y, Siegal, M & Sinha, H 2012, 'Polygenic cis-regulatory adaptation in the evolution of yeast pathogenicity', Genome Research, vol. 22, no. 10, pp. 1930-1939. https://doi.org/10.1101/gr.134080.111
Fraser HB, Levy S, Chavan A, Shah HB, Perez JC, Zhou Y et al. Polygenic cis-regulatory adaptation in the evolution of yeast pathogenicity. Genome Research. 2012 Oct;22(10):1930-1939. https://doi.org/10.1101/gr.134080.111
Fraser, Hunter B. ; Levy, Sasha ; Chavan, Arun ; Shah, Hiral B. ; Perez, J. Christian ; Zhou, Yiqi ; Siegal, Mark ; Sinha, Himanshu. / Polygenic cis-regulatory adaptation in the evolution of yeast pathogenicity. In: Genome Research. 2012 ; Vol. 22, No. 10. pp. 1930-1939.
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