Published June 28, 2023 | Version v1
Dataset Open

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

  • 1. University of Miami

Description

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.

Notes

Associated code can be found: https://github.com/mxd1288/Genotypic_drivers.git

Funding provided by: National Science Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/501100008982
Award Number: IOS 1556396

Funding provided by: National Science Foundation
Crossref Funder Registry ID: http://dx.doi.org/10.13039/100000001
Award Number: 652 IOS 1754437

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