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

Abstract

Heritable variation in a gene's expression arises from mutations impacting <i>cis</i>- and <i>trans</i>-acting components of its regulatory network. Here, we investigate how <i>trans</i>-regulatory mutations are distributed within the genome and within a gene regulatory network by identifying and characterizing 69 mutations with <i>trans</i>-regulatory effects on expression of the same focal gene in <i>Saccharomyces cerevisiae</i>. Relative to 1766 mutations without effects on expression of this focal gene, we found that these <i>trans</i>-regulatory mutations were enriched in coding sequences of transcription factors previously predicted to regulate expression of the focal gene. However, over 90% of the <i>trans</i>-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 <i>trans</i>, revealing properties of <i>trans</i>-regulatory mutations that provide the raw material for <i>trans</i>-regulatory variation segregating within natural populations.