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Transcriptional Derepression Uncovers Cryptic Higher-Order Genetic Interactions

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Some genetic polymorphisms have phenotypic effects that are masked under most conditions, but can be revealed by mutations or environmental change. The genetic and molecular mechanisms that suppress and uncover these cryptic genetic variants are important to understand. Here, we show that a single mutation in a yeast cross causes a major phenotypic change through its genetic interactions with two specific combinations of cryptic variants in six genes. This result suggests that in some cases cryptic variants themselves play roles in revealing their own phenotypic effects through their genetic interactions with each other and the mutations that reveal them. We also demonstrate that most of the genes harboring cryptic variation in our system are transcription factors, a finding that supports an important role for perturbation of gene regulatory networks in the uncovering of cryptic variation. As a final part of our study, we interrogate how a mutation exposes combinations of cryptic variants and obtain evidence that it does so by disrupting the silencing of one or more genes that must be expressed for the cryptic variants to exert their effects. To prove this point, we delete the transcriptional repressor that mediates this silencing and demonstrate that this deletion reveals a similar set of cryptic variants to the ones that were discovered in the initial mutant background. These findings advance our understanding of the genetic and molecular mechanisms that reveal cryptic variation.

Vyšlo v časopise: Transcriptional Derepression Uncovers Cryptic Higher-Order Genetic Interactions. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005606
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005606

Souhrn

Some genetic polymorphisms have phenotypic effects that are masked under most conditions, but can be revealed by mutations or environmental change. The genetic and molecular mechanisms that suppress and uncover these cryptic genetic variants are important to understand. Here, we show that a single mutation in a yeast cross causes a major phenotypic change through its genetic interactions with two specific combinations of cryptic variants in six genes. This result suggests that in some cases cryptic variants themselves play roles in revealing their own phenotypic effects through their genetic interactions with each other and the mutations that reveal them. We also demonstrate that most of the genes harboring cryptic variation in our system are transcription factors, a finding that supports an important role for perturbation of gene regulatory networks in the uncovering of cryptic variation. As a final part of our study, we interrogate how a mutation exposes combinations of cryptic variants and obtain evidence that it does so by disrupting the silencing of one or more genes that must be expressed for the cryptic variants to exert their effects. To prove this point, we delete the transcriptional repressor that mediates this silencing and demonstrate that this deletion reveals a similar set of cryptic variants to the ones that were discovered in the initial mutant background. These findings advance our understanding of the genetic and molecular mechanisms that reveal cryptic variation.

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