RESUMO
Unraveling the genetic sources of gene expression variation is essential to better understand the origins of phenotypic diversity in natural populations. Genome-wide association studies identified thousands of variants involved in gene expression variation, however, variants detected only explain part of the heritability. In fact, variants such as low-frequency and structural variants (SVs) are poorly captured in association studies. To assess the impact of these variants on gene expression variation, we explored a half-diallel panel composed of 323 hybrids originated from pairwise crosses of 26 natural Saccharomyces cerevisiae isolates. Using short- and long-read sequencing strategies, we established an exhaustive catalog of single nucleotide polymorphisms (SNPs) and SVs for this panel. Combining this dataset with the transcriptomes of all hybrids, we comprehensively mapped SNPs and SVs associated with gene expression variation. While SVs impact gene expression variation, SNPs exhibit a higher effect size with an overrepresentation of low-frequency variants compared to common ones. These results reinforce the importance of dissecting the heritability of complex traits with a comprehensive catalog of genetic variants at the population level.
Assuntos
Estudo de Associação Genômica Ampla , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Expressão Gênica , Polimorfismo de Nucleotídeo Único/genética , Variação GenéticaRESUMO
Gene expression variation, an essential step between genotype and phenotype, is collectively controlled by local (cis) and distant (trans) regulatory changes. Nevertheless, how these regulatory elements differentially influence gene expression variation remains unclear. Here, we bridge this gap by analyzing the transcriptomes of a large diallel panel consisting of 323 unique hybrids originating from genetically divergent Saccharomyces cerevisiae isolates. Our analysis across 5,087 transcript abundance traits showed that non-additive components account for 36% of the gene expression variance on average. By comparing allele-specific read counts in parent-hybrid trios, we found that trans-regulatory changes underlie the majority of gene expression variation in the population. Remarkably, most cis-regulatory variations are also exaggerated or attenuated by additional trans effects. Overall, we showed that the transcriptome is globally buffered at the genetic level mainly due to trans-regulatory variation in the population.
Assuntos
Saccharomyces cerevisiae , Transcriptoma , Transcriptoma/genética , Saccharomyces cerevisiae/genética , Alelos , Fenótipo , GenótipoRESUMO
Gene expression variation, an essential step between genomic variation and phenotypic landscape, is collectively controlled by local (cis) and distant (trans) regulatory changes. Nevertheless, how these regulatory elements differentially influence the heritability of expression traits remains unclear. Here, we bridge this gap by analyzing the transcriptomes of a large diallel panel consisting of 323 unique hybrids originated from genetically divergent yeast isolates. We estimated the broad- and narrow-sense heritability across 5,087 transcript abundance traits and showed that non-additive components account for 36% of the phenotypic variance on average. By comparing allelic expression ratios in the hybrid and the corresponding parental pair, we identified regulatory changes in 25% of all cases, with a majority acting in trans. We further showed that trans-regulation could underlie coordinated expression variation across highly connected genes, resulting in significantly higher non-additive variance and most likely in some of the missing heritability of gene expression traits.
RESUMO
Unraveling the genetic sources of gene expression variation is essential to better understand the origins of phenotypic diversity in natural populations. Genome-wide association studies identified thousands of variants involved in gene expression variation, however, variants detected only explain part of the heritability. In fact, variants such as low-frequency and structural variants (SVs) are poorly captured in association studies. To assess the impact of these variants on gene expression variation, we explored a half-diallel panel composed of 323 hybrids originated from pairwise crosses of 26 natural Saccharomyces cerevisiae isolates. Using short- and long-read sequencing strategies, we established an exhaustive catalog of single nucleotide polymorphisms (SNPs) and SVs for this panel. Combining this dataset with the transcriptomes of all hybrids, we comprehensively mapped SNPs and SVs associated with gene expression variation. While SVs impact gene expression variation, SNPs exhibit a higher effect size with an overrepresentation of low-frequency variants compared to common ones. These results reinforce the importance of dissecting the heritability of complex traits with a comprehensive catalog of genetic variants at the population level.
