Mutational sources of trans-regulatory variation affecting gene expression in Saccharomyces cerevisiae

Author:

Duveau Fabien12ORCID,Vande Zande Petra3,Metzger Brian PH1ORCID,Diaz Crisandra J3,Walker Elizabeth A1,Tryban Stephen1,Siddiq Mohammad A1,Yang Bing3,Wittkopp Patricia J13ORCID

Affiliation:

1. Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, United States

2. Laboratory of Biology and Modeling of the Cell, Ecole Normale Supérieure de Lyon, CNRS, Université Claude Bernard Lyon, Université de Lyon, Lyon, France

3. Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United States

Abstract

Heritable variation in a gene’s expression arises from mutations impacting cis- and trans-acting components of its regulatory network. Here, we investigate how trans-regulatory mutations are distributed within the genome and within a gene regulatory network by identifying and characterizing 69 mutations with trans-regulatory effects on expression of the same focal gene in Saccharomyces cerevisiae. Relative to 1766 mutations without effects on expression of this focal gene, we found that these trans-regulatory mutations were enriched in coding sequences of transcription factors previously predicted to regulate expression of the focal gene. However, over 90% of the trans-regulatory mutations identified mapped to other types of genes involved in diverse biological processes including chromatin state, metabolism, and signal transduction. These data show how genetic changes in diverse types of genes can impact a gene’s expression in trans, revealing properties of trans-regulatory mutations that provide the raw material for trans-regulatory variation segregating within natural populations.

Funder

National Institutes of Health

European Molecular Biology Organization

National Science Foundation

University of Michigan

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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