Oct 21, 2015

Transcriptional Derepression Uncovers Cryptic Higher-Order Genetic Interactions

PLoS Genetics
Matthew B Taylor, Ian M Ehrenreich

Abstract

Disruption of certain genes can reveal cryptic genetic variants that do not typically show phenotypic effects. Because this phenomenon, which is referred to as 'phenotypic capacitance', is a potential source of trait variation and disease risk, it is important to understand how it arises at the genetic and molecular levels. Here, we use a cryptic colony morphology trait that segregates in a yeast cross to explore the mechanisms underlying phenotypic capacitance. We find that the colony trait is expressed when a mutation in IRA2, a negative regulator of the Ras pathway, co-occurs with specific combinations of cryptic variants in six genes. Four of these genes encode transcription factors that act downstream of the Ras pathway, indicating that the phenotype involves genetically complex changes in the transcriptional regulation of Ras targets. We provide evidence that the IRA2 mutation reveals the phenotypic effects of the cryptic variants by disrupting the transcriptional silencing of one or more genes that contribute to the trait. Supporting this role for the IRA2 mutation, deletion of SFL1, a repressor that acts downstream of the Ras pathway, also reveals the phenotype, largely due to the same cryptic variants that were detecte...Continue Reading

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  • Citations16

Citations

Mentioned in this Paper

Saccharomyces cerevisiae Proteins
IRA2 protein, S cerevisiae
Biochemical Pathway
SFL1 protein, S cerevisiae
Transcriptional Regulation
CFC1 gene
Transcription Repressor/Corepressor
Genes
IRA2
Regulation of Biological Process

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