title: Genetic influences on translation in yeast.
abstract: 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.
authors.affiliation: Department of Human Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Albert
authors.affiliation: Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, Center for RNA Systems Biology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Dale
authors.initials: D
authors.lastname: Muzzey
authors.affiliation: Department of Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, Center for RNA Systems Biology, and Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Weissman
authors.affiliation: Department of Human Genetics, University of California, Los Angeles, Los Angeles, California, United States of America; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, California, United States of America; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Leonid
authors.initials: L
authors.lastname: Kruglyak
mesh_terms: D000483:Alleles; D030541:Databases, Genetic; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D006801:Humans; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D012333:RNA, Messenger