title: Diverse genetic architectures lead to the same cryptic phenotype in a yeast cross.
abstract: Cryptic genetic variants that do not typically influence traits can interact epistatically with each other and mutations to cause unexpected phenotypes. To improve understanding of the genetic architectures and molecular mechanisms that underlie these interactions, we comprehensively dissected the genetic bases of 17 independent instances of the same cryptic colony phenotype in a yeast cross. In eight cases, the phenotype resulted from a genetic interaction between a de novo mutation and one or more cryptic variants. The number and identities of detected cryptic variants depended on the mutated gene. In the nine remaining cases, the phenotype arose without a de novo mutation due to two different classes of higher-order genetic interactions that only involve cryptic variants. Our results may be relevant to other species and disease, as most of the mutations and cryptic variants identified in our study reside in components of a partially conserved and oncogenic signalling pathway.
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Taylor
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Joann
authors.initials: J
authors.lastname: Phan
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Lee
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Madelyn
authors.initials: M
authors.lastname: McCadden
authors.affiliation: Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Ehrenreich
mesh_terms: D002874:Chromosome Mapping; D017124:Conserved Sequence; D003433:Crosses, Genetic; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D005838:Genotype; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D005656:Fungal Proteins; D015513:Oncogene Proteins