DivergentMLS1promoters lie on a fitness plateau for gene expression

Abstract

Qualitative patterns of gene activation and repression are often conserved despite an abundance of quantitative variation in expression levels within and between species. A major challenge to interpreting patterns of expression divergence is knowing which changes in gene expression affect fitness. To characterize the fitness effects of gene expression divergence, we placed orthologous promoters from eight yeast species upstream of malate synthase (MLS1) in Saccharomyces cerevisiae. As expected, we found these promoters varied in their expression level under activated and repressed conditions as well as in their dynamic response following loss of glucose repression. Despite these differences, only a single promoter driving near basal levels of expression caused a detectable loss of fitness. We conclude that the MLS1 promoter lies on a fitness plateau whereby even large changes in gene expression can be tolerated without a substantial loss of fitness.

Fitness effects ofcis-regulatory variants in theSaccharomyces cerevisiae TDH3promoter

“…Finding that most cis-regulatory mutations and polymorphisms cause changes in TDH3 expression level within the observed fitness plateau indicates that their effects are largely buffered at the fitness level, conferring robustness in the activity of the wild type P TDH3 allele against new mutations, at least in the environment assayed. Non-linear fitness functions with plateaus located around the wild type level of gene expression have previously been described in S. cerevisiae for the LCB2 gene using an inducible promoter (Rest et al 2013) as well as for other yeast genes using synthetic promoters (Keren et al 2016) or interspecific comparisons (Bergen et al 2016), and are consistent with predictions from metabolic flux control theory (Kacser and Burns 1973). These observations suggest that fitness plateaus might be common for expression-fitness functions and might play an important role in shaping the diversity of gene expression levels observed in natural populations.…”