Determining how genotype translates to phenotype is a complex issue. While rapid progress has been made in linking nuclear genome variations to population traits, much less is known about whether and how extra-chromosomal elements shape phenotypic changes. Using the yeast Saccharomyces cerevisiae as our model, we analyzed the phenotypic contributions from two classes of non-chromosomal elements— mitochondrial DNA and endogenous double-stranded RNA viruses. S. cerevisiae shares highly conserved cellular processes with humans, is ideally suited for Mendelian as well as non-Mendelian genetics, and is markedly similar to clinically relevant pathogenic fungi, making it ideal for our studies.
Through a comprehensive sequence analysis of mitochondrial DNA from 100 geographically diverse strains of S. cerevisiae, we firstly identified a wide range of mitochondrial DNA-associated variations including copy number changes, single nucleotide polymorphisms, indels, and presence/absence of introns within select mitochondrial genes. Subsequently, we created a series of iso(genic)-nuclear diploid strains, each carrying a single, unique mitochondrial genotype, and tested these under diverse environmental conditions to systematically assess the contribution of individual mitochondrial genomes to phenotype. Our results indicate that mitochondrial variations significantly influence phenotypic outcome.
Additionally, we genotyped our 100-genome collection for the presence and absence of several naturally occurring viral dsRNA elements and found that up to a third of the population harbors the well-characterized dsRNA virus L-A. We observed pronounced L-A dependent phenotypic effects in our analysis of isogenic +/- L-A strain pairs. Interestingly, both mitochondrial and L-A genotypes were found to significantly influence several phenotypes, further underscoring the contributions of non-chromosomal genetic determinants to quantitative trait variations.
Our studies highlight the complexity of gene-environment interactions that ultimately determine fitness and survival. Future work would be aimed at identification of the precise genetic loci to understand the mechanistic basis of such phenotypic changes.