Dissecting the causes of natural variation in protein expression dynamics

Synopsis

Yeast cells respond to their environment by coordinating the expression of thousands of genes to produce a specific complement of millions of protein molecules. Natural genetic variation has the potential to impact protein expression dynamics by acting at different levels, including transcription, mRNA stability, translation, and protein stability. The link between genetic variation and mRNA expression divergence is well established, however, the importance of genetic variation acting on protein translation and degradation rates is poorly resolved. To distinguish genetic variation acting directly on mRNA levels from genetic variation acting directly on protein levels, and to dissect how these two types of variation affect different phases of a dynamic cellular response, we measured both mRNA and protein expression dynamics in the Saccharomyces cerevisiae laboratory strain S288c and the clinical strain YJM145. I will present our analysis of variation in protein expression dynamics in the mating pheromone response network. Our results suggest that genetic variation commonly acts on protein translation and degradation rates, independently of mRNA levels. I will discuss our ongoing efforts to dissect this new class of genetic variants, including whole proteome analysis, mapping causative variants, and characterizing molecular mechanisms.