Aug 2, 2015

Regulatory Rewiring in a Cross Causes Extensive Genetic Heterogeneity

Takeshi MatsuiIan M Ehrenreich


Genetic heterogeneity occurs when individuals express similar phenotypes as a result of different underlying mechanisms. Although such heterogeneity is known to be a potential source of unexplained heritability in genetic mapping studies, its prevalence and molecular basis are not fully understood. Here we show that substantial genetic heterogeneity underlies a model phenotype--the ability to grow invasively--in a cross of two Saccharomyces cerevisiae strains. The heterogeneous basis of this trait across genotypes and environments makes it difficult to detect causal loci with standard genetic mapping techniques. However, using selective genotyping in the original cross, as well as in targeted backcrosses, we detected four loci that contribute to differences in the ability to grow invasively. Identification of causal genes at these loci suggests that they act by changing the underlying regulatory architecture of invasion. We verified this point by deleting many of the known transcriptional activators of invasion, as well as the gene encoding the cell surface protein Flo11 from five relevant segregants and showing that these individuals differ in the genes they require for invasion. Our work illustrates the extensive genetic hete...Continue Reading

Mentioned in this Paper

Saccharomyces cerevisiae Proteins
Quantitative Trait Loci
Saccharomyces cerevisiae allergenic extract
Transcription, Genetic
Genome Mapping
Genetic Heterogeneity
Cell Surface
Gene Regulatory Networks

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