Divergence of the Yeast Transcription Factor FZF1 Affects Sulfite Resistance

Changes in gene expression are commonly observed during evolution. However, the phenotypic consequences of expression divergence are frequently unknown and difficult to measure. Transcriptional regulators provide a mechanism by which phenotypic divergence can occur through multiple, coordinated changes in gene expression during development or in response to environmental changes. Yet, some changes in transcriptional regulators may be constrained by their pleiotropic effects on gene expression. Here, we use a genome-wide screen for promoters that are likely to have diverged in function and identify a yeast transcription factor, FZF1, that has evolved substantial differences in its ability to confer resistance to sulfites. Chimeric alleles from four Saccharomyces species show that divergence in FZF1 activity is due to changes in both its coding and upstream noncoding sequence. Between the two closest species, noncoding changes affect the expression of FZF1, whereas coding changes affect the expression of SSU1, a sulfite efflux pump activated by FZF1. Both coding and noncoding changes also affect the expression of many other genes. Our results show how divergence in the coding and promoter region of a transcription factor alters the response to an environmental stress. Changes in gene regulation are thought to play an important role in evolution. While variation in gene expression between species is common, it is hard to identify the phenotypic consequences of this variation since many changes in gene expression may have subtle or no phenotypic effects. In this study, we investigate changes in sulfite resistance and gene expression caused by the transcription factor, FZF1, that has evolved rapidly during the divergence of related yeast species. We find that divergence in the ability of FZF1 to confer sulfite resistance is mediated by changes in its expression as well as changes in its protein structure, both of which cause changes in the expression of other genes. Our results show how the combination of multiple changes within a transcription factor can produce substantial changes in phenotype and the expression of many genes.