A cradle-to-grave analysis of cis-regulatory variation in yeast
Andrie, Jennifer Margaret
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Cis-regulatory variation is an important source of phenotypic variation within populations and a major target of adaptive divergence between species. However, the molecular processes that are influenced by cis-regulatory variation remain poorly understood. To this end, we crossed two genetically diverse wild-derived strains of Saccharomyces cerevisiae and studied allele-specific differences in six molecular phenotypes, including chromatin structure, rates of RNA transcription, decay and translation, RNA secondary structure, and binding of proteins to RNA. Furthermore, we performed high-coverage sequencing of both the genome, using PacBio, and the transcriptome, and de novo assembled each parental strain to mitigate read mapping biases and ensure accurate estimates of allele-specific phenotypes. We show that cis-regulatory variation has pervasive influence on the conversion of genotype into phenotype, and that pleiotropy is a predominant feature in the architectural landscape of cis-regulatory mutations. Our comprehensive data also provide novel mechanistic insights into cis-regulatory variation, revealing an important role for RNA secondary structure and RNA binding protein-RNA interactions in determining RNA decay rate and translation efficiency. Overall, we find that relationships between allelic differences in the measured molecular phenotypes are highly complex. Our data represent the most comprehensive analysis conducted to date of how genetic variation influences gene expression and, therefore, provide, an important advancement toward the understanding of how genetic variation produces phenotypic variation.
- Genetics