Pairwise and higher-order genetic interactions during the evolution of a tRNA

Pairwise and higher-order genetic interactions during the evolution of a tRNA A central question in genetics and evolution is the extent to which the outcomes of mutations change depending on the genetic context in which they occur 1–3 . Pairwise interactions between mutations have been systematically mapped within 4–18 and between 19 genes, and have been shown to contribute substantially to phenotypic variation among individuals 20 . However, the extent to which genetic interactions themselves are stable or dynamic across genotypes is unclear 21, 22 . Here we quantify more than 45,000 genetic interactions between the same 87 pairs of mutations across more than 500 closely related genotypes of a yeast tRNA. Notably, all pairs of mutations interacted in at least 9% of genetic backgrounds and all pairs switched from interacting positively to interacting negatively in different genotypes (false discovery rate < 0.1). Higher-order interactions are also abundant and dynamic across genotypes. The epistasis in this tRNA means that all individual mutations switch from detrimental to beneficial, even in closely related genotypes. As a consequence, accurate genetic prediction requires mutation effects to be measured across different genetic backgrounds and the use of  higher-order epistatic terms. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Springer Journals

Pairwise and higher-order genetic interactions during the evolution of a tRNA

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Publisher
Springer Journals
Copyright
Copyright © 2018 by Macmillan Publishers Ltd., part of Springer Nature
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
ISSN
0028-0836
eISSN
1476-4687
D.O.I.
10.1038/s41586-018-0170-7
Publisher site
See Article on Publisher Site

Abstract

A central question in genetics and evolution is the extent to which the outcomes of mutations change depending on the genetic context in which they occur 1–3 . Pairwise interactions between mutations have been systematically mapped within 4–18 and between 19 genes, and have been shown to contribute substantially to phenotypic variation among individuals 20 . However, the extent to which genetic interactions themselves are stable or dynamic across genotypes is unclear 21, 22 . Here we quantify more than 45,000 genetic interactions between the same 87 pairs of mutations across more than 500 closely related genotypes of a yeast tRNA. Notably, all pairs of mutations interacted in at least 9% of genetic backgrounds and all pairs switched from interacting positively to interacting negatively in different genotypes (false discovery rate < 0.1). Higher-order interactions are also abundant and dynamic across genotypes. The epistasis in this tRNA means that all individual mutations switch from detrimental to beneficial, even in closely related genotypes. As a consequence, accurate genetic prediction requires mutation effects to be measured across different genetic backgrounds and the use of  higher-order epistatic terms.

Journal

NatureSpringer Journals

Published: May 30, 2018

References

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