Pleiotropic effects of trans-regulatory mutations on gene expression and fitness

Variation in gene expression arises from cis- and trans-regulatory mutations, which contribute differentially to expression divergence. Here, we compare the impacts on gene expression and fitness for cis- and trans-regulatory mutations affecting expression of the TDH3 gene in Saccharomyces cerevisiae. We use the effects of cis-regulatory mutations to isolate effects of trans-regulatory mutations caused by impacts on TDH3 from pleiotropic impacts on other genes, providing a rare distribution of pleiotropic effects. These pleiotropic effects were often, but not always, deleterious. For cis- and trans-regulatory mutations with similar effects on TDH3, trans-regulatory mutations had more widespread effects on gene expression, with distinct impacts on expression of genes downstream of TDH3. These differences between cis-and trans-regulatory mutations help explain their different contributions to regulatory evolution. Overall design: Each of four replicates is one sequencing lane composed of multiplexed library preps for 35 trans-regulatory mutants to TDH3, 3 deletion mutants, 3 alpha wild type controls, 1 a wild type control, 4 cis-regulatory mutants underexpressing TDH3, 1 duplication and cis-regulatory mutant of the TDH3 locus, and one duplication wild type control. A few strains are missing from each replicate due to failed library preps, resulting in 188 samples Please note that the Strain*txt files are the DESeq2 output for each strain relative to a control and are generated from the data of all four replicate samples for each strain, as indiated in the corresponding sample description field.