Regulatory Rewiring in a Cross Causes Extensive Genetic Heterogeneity

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....

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Bibliographic Details
Published in:Genetics (Austin) 2015-10, Vol.201 (2), p.769-777
Main Authors: Matsui, Takeshi, Linder, Robert, Phan, Joann, Seidl, Fabian, Ehrenreich, Ian M
Format: Article
Language:English
Subjects:
Chromosome Mapping
Crosses, Genetic
Genetic Heterogeneity
Genetics
Genotype
Genotype & phenotype
Humans
Investigations
Membrane Glycoproteins - genetics
Phenotype
Quantitative Trait Loci - genetics
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae Proteins - genetics
Yeast
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Summary: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 heterogeneity that can underlie a trait and suggests that regulatory rewiring is a basic mechanism that gives rise to this heterogeneity.
ISSN:1943-2631
0016-6731
1943-2631
DOI:10.1534/genetics.115.180661