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Harmonious genetic combinations rewire regulatory networks and flip gene essentiality.

Abstract：

:We lack an understanding of how the full range of genetic variants that occur in individuals can interact. To address this shortcoming, here we combine diverse mutations between genes in a model regulatory network, the galactose (GAL) switch of budding yeast. The effects of thousands of pairs of mutations fall into a limited number of phenotypic classes. While these effects are mostly predictable using simple rules that capture the 'stereotypical' genetic interactions of the network, some double mutants have unexpected outcomes including constituting alternative functional switches. Each of these 'harmonious' genetic combinations exhibits altered dependency on other regulatory genes. These cases illustrate how both pairwise and higher epistasis determines gene essentiality and how combinations of mutations rewire regulatory networks. Together, our results provide an overview of how broad spectra of mutations interact, how these interactions can be predicted, and how diverse genetic solutions can achieve 'wild-type' phenotypic behavior.

journal_name

Nat Commun

journal_title

Nature communications

authors

New AM,Lehner B

doi

10.1038/s41467-019-11523-z

subject

Has Abstract

pub_date

2019-08-14 00:00:00

pages

3657

issue

1

issn

2041-1723

pii

10.1038/s41467-019-11523-z

journal_volume

10

pub_type

杂志文章

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