Genetic Influences on Translation in Yeast
Heritable differences in gene expression between individuals are an important source of phenotypic variation. The question of how closely the effects of genetic variation on protein levels mirror those on mRNA levels remains open. Here, we addressed this question by using ribosome profiling to examine how genetic differences between two strains of the yeast S. cerevisiae affect translation. Strain differences in translation were observed for hundreds of genes. Allele specific measurements in the diploid hybrid between the two strains revealed roughly half as many cis-acting effects on translation as were observed for mRNA levels. In both the parents and the hybrid, most effects on translation were of small magnitude, such that the direction of an mRNA difference was typically reflected in a concordant footprint difference. The relative importance of cis and trans acting variation on footprint levels was similar to that for mRNA levels. There was a tendency for translation to cause larger footprint differences than expected given the respective mRNA differences. This is in contrast to translational differences between yeast species that have been reported to more often oppose than reinforce mRNA differences. Finally, we catalogued instances of premature translation termination in the two yeast strains and also found several instances where erroneous reference gene annotations lead to apparent nonsense mutations that in fact reside outside of the translated gene body. Overall, genetic influences on translation subtly modulate gene expression differences, and translation does not create strong discrepancies between genetic influences on mRNA and protein levels. Author summary Individuals in a species differ from each other in many ways. For many traits, a fraction of this variation is genetic – it is caused by DNA sequence variants in the genome of each individual. Some of these variants influence traits by altering how much certain genes are expressed, i.e. how many mRNA and protein molecules are made in different individuals. Surprisingly, earlier work has found that the effects of genetic variants on mRNA and protein levels for the same genes appear to be very different. Many variants appeared to influence only mRNA (but not protein) levels, and vice versa. In this paper, we studied this question by using a technique called “ribosome profiling” to measure translation (the cellular process of reading mRNA molecules and synthesizing protein molecules) in two yeast strains. We found that the genetic differences between these two strains influence translation for hundreds of genes. Because most of these effects were small in magnitude, they explain at most a small fraction of the discrepancies between the effects of genetic variants on mRNA and protein levels.