The complex underpinnings of genetic background effects
Martin N. Mullis, Takeshi Matsui, Rachel Schell, Ryan Foree & Ian M. Ehrenreich
Nature Communications volume 9, Article number: 3548 (2018)
Article | OPEN | Published: 17 September 2018
Source/Fonte: Evolution Berkeley
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.
Acknowledgements
We thank Norm Arnheim, Mark Chaisson, Matt Dean, Sasha Levy, David Pfennig, and Kevin Roy for comments on a draft of this manuscript. We also thank Alessandro Coradini, Jonathan Lee, and Fabian Seidl for input during the execution of this project and writing of this paper. The research described in this manuscript was supported by grant R01GM110255 from the National Institutes of Health, as well as a Computational and Evolutionary Molecular Biology fellowship from the Alfred P. Sloan Foundation to I.M.E. and a Research Enhancement Fellowship from the USC Graduate School to M.N.M. Many of the analyses described in this paper were performed on the USC High-Performance Computing cluster.
Author information
Author notes
These authors contributed equally: Martin N. Mullis, Takeshi Matsui, Rachel Schell.
Affiliations
Molecular and Computational Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, 90089-2910, USA
Martin N. Mullis, Takeshi Matsui, Rachel Schell, Ryan Foree & Ian M. Ehrenreich
Contributions
M.N.M., T.M., R.S. and I.M.E. conceptualized this project. M.N.M., T.M., R.S. and R.F. performed experiments. M.N.M., T.M. and I.M.E. analyzed data. M.N.M., T.M., R.S. and I.M.E. wrote the paper.
Competing interests
The authors declare no competing interests.
Corresponding authors
Correspondence to Martin N. Mullis or Takeshi Matsui or Ian M. Ehrenreich.
FREE PDF GRATIS: Nature Communications Sup. Info. Reviewers' File Description of Additional Info
