Prof. Joseph Schacherer and his group are using population and functional genomics to better understand the genotype-phenotype relationship within species.
Abstract
Gene expression is crucial for translating genotypes into phenotypes, yet our understanding of transcriptome and proteome variation at the species level remains limited. We generated and analyzed the pan-transcriptome of approximately 1,000 Saccharomyces cerevisiae natural isolates, covering 4,977 core and 1,468 accessory genes, and found that the accessory genome significantly drives transcriptome divergence. Interestingly, differential expression patterns reveal clear transcriptional signatures related to different subpopulations, mainly domesticated. Genome-wide association analyses showed that accessory genes are linked to more variants with larger effect sizes, highlighting their critical role in the transcriptional landscape. Additionally, we determined the quantitative proteomes of the same collection of natural isolates, discovering a weak correlation between mRNA and protein abundances at the population gene level. The protein coexpression network also reflects major biological functions, while differential expression patterns reveal again proteomic signatures specific to domesticated populations. In addition, genetic association analyses showed poor overlap (3%) between variants associated with protein (pQTL) and transcript (eQTL) levels, indicating distinct genetic bases likely due to protein turnover.
Our integrated approach underscores the importance of combining transcriptomic and proteomic analyses to understand the genotype-phenotype relationship. Domestication processes played a pivotal role in transcript and protein abundance variations. Overall, this comprehensive view also helps to have a better insight the complex mechanisms linking genetic variation to phenotypic diversity.