Trans-Acting Genotypes Associated with mRNA Expression Affect Metabolic and Thermal Tolerance Traits

Abstract

Evolutionary processes driving physiological trait variation depend on the underlying genomic mechanisms. Evolution of these mechanisms depends on the genetic complexity (involving many genes) and how gene expression impacting the traits is converted to phenotype. Yet, genomic mechanisms that impact physiological traits are diverse and context dependent (e.g., vary by environment and tissues), making them difficult to discern. We examine the relationships between genotype, mRNA expression, and physiological traits to discern the genetic complexity and whether the gene expression affecting the physiological traits is primarily cis- or trans-acting. We use low-coverage whole genome sequencing and heart- or brain-specific mRNA expression to identify polymorphisms directly associated with physiological traits and expressed quantitative trait loci (eQTL) indirectly associated with variation in six temperature specific physiological traits (standard metabolic rate, thermal tolerance, and four substrate specific cardiac metabolic rates). Focusing on a select set of mRNAs belonging to co-expression modules that explain up to 82% of temperature specific traits, we identified hundreds of significant eQTL for mRNA whose expression affects physiological traits. Surprisingly, most eQTL (97.4% for heart and 96.7% for brain) were trans-acting. This could be due to higher effect size of trans- versus cis-acting eQTL for mRNAs that are central to co-expression modules. That is, we may have enhanced the identification of trans-acting factors by looking for single nucleotide polymorphisms associated with mRNAs in co-expression modules that broadly influence gene expression patterns. Overall, these data indicate that the genomic mechanism driving physiological variation across environments is driven by trans-acting heart- or brain-specific mRNA expression.

Keywords: GWAS; WGCNA; eQTL; mRNA expression; metabolism; thermal tolerance.