Trans-acting genotypes drive mRNA expression affecting metabolic and thermal tolerance traits

Evolutionary processes driving physiological trait variation depend on the
underlying genomic mechanisms. Evolution of these mechanisms depends on
whether traits are genetically complex (involving many genes) and how gene
expression that impacts the traits is converted to phenotype. Yet, genomic
mechanisms that impact physiological traits are diverse and
context-dependent (e.g., vary by environment or among tissues), making
them difficult to discern. Here 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 tissue-specific mRNA expression among individuals to
identify polymorphisms directly associated with physiological traits and
expressed quantitative trait loci (eQTL) driving variation in six
temperature-specific physiological traits (standard metabolic rate,
thermal tolerance, and four substrate-specific cardiac metabolic rates).
Not surprisingly, there were few, only five, SNPs directly associated with
physiological traits. Yet, by focusing on a select set of mRNAs belonging
to co-expression modules that explain up to 82% of temperature specific
(12°C or 28°C) metabolism and thermal tolerance, 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) of eQTL were
trans-acting. This could be due to higher effect size or greater
importance of trans versus cis-acting eQTLs for mRNAs that are central to
co-expression modules. That is, we may have enhanced the identification of
trans-acting factors by looking for SNPs associated with mRNAs in
co-expression modules that are known to be correlated with the expression
of 10s or 100s of other genes, and thus have identified eQTLs with
widespread effects on broad gene expression patterns. Overall, these data
indicate that the genomic mechanism driving physiological variation across
environments is driven by trans-acting tissue-specific mRNA expression.