The complex underpinnings of genetic background effects

Nature Communications
Martin N MullisIan M Ehrenreich

Abstract

Genetic interactions between mutations and standing polymorphisms can cause mutations to show distinct phenotypic effects in different individuals. To characterize the genetic architecture of these so-called background effects, we genotype 1411 wild-type and mutant yeast cross progeny and measure their growth in 10 environments. Using these data, we map 1086 interactions between segregating loci and 7 different gene knockouts. Each knockout exhibits between 73 and 543 interactions, with 89% of all interactions involving higher-order epistasis between a knockout and multiple loci. Identified loci interact with as few as one knockout and as many as all seven knockouts. In mutants, loci interacting with fewer and more knockouts tend to show enhanced and reduced phenotypic effects, respectively. Cross-environment analysis reveals that most interactions between the knockouts and segregating loci also involve the environment. These results illustrate the complicated interactions between mutations, standing polymorphisms, and the environment that cause background effects.

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Citations

Dec 7, 2018·Clinical Genetics·Jung-Wook KimJan C-C Hu
Feb 23, 2019·Genetics·Jonathan T LeeIan M Ehrenreich
Dec 31, 2019·Molecular Systems Biology·Marco GalardiniPedro Beltrao
Sep 19, 2019·Molecular Biology and Evolution·Rhastin A D CastroSebastien Gagneux
May 15, 2019·Annual Review of Genomics and Human Genetics·Júlia DomingoBen Lehner
Feb 26, 2019·Proceedings of the National Academy of Sciences of the United States of America·Jing HouCharles Boone
Oct 18, 2020·Chromosoma·Emily R WesleyKatherine Kretovich Billmyre
Sep 29, 2020·Genome Biology and Evolution·Danilo PereiraDaniel Croll
May 8, 2021·Science·Michael CostanzoBrenda Andrews
May 28, 2021·Molecular Systems Biology·Leopold PartsJolanda van Leeuwen
Aug 27, 2021·Ecotoxicology and Environmental Safety·Shunli JiangQing Lu

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Methods Mentioned

BETA
gene knockouts
PCR
PCRs

Software Mentioned

R package lsmeans
R package ggtern
R
SAMTOOLS
ImageJ
HMM
BWA

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