Variation between long-diverged fungal species.
Fungi specialize to their environment in amazing ways. When a fungal species from one niche differs radically from its relatives elsewhere, we would love to know the mechanism at play. In many cases the underlying adaptive alleles are a mystery, especially if they arose long ago. The main roadblock to date has been that most experimental tools in evolutionary genetics research are only applicable to comparison across strains, not species. Ongoing work in the lab is devoted to breaking through this limitation. We developed a novel approach to map the genetic basis of differences between distantly related species through reciprocal hemizygote analysis of interspecific hybrids.
A transposon (rectangle) disrupts the allele from S. cerevisiae (blue) or S. paradoxus (orange) of a gene (YFG) in an interspecific hybrid (green). Clones lacking the prothermotolerance allele grow poorly at 39°C (dashed outlines), as measured by sequencing and reported in smoothed histograms (traces, colored to indicate the species’ allele that is not disrupted)
Our method reveals the nucleotide-level variants that a given fungus has used to adapt to its environment over evolutionary time. The pilot project uses thermotolerance in Saccharomyces yeast as a testbed, with the promise of extension to various phenotypes in many other eukaryotes. For more information, see our bioRxiv pre-print, in press with Nature Genetics.
In many cases, adaptation may be the result of multiple, subtly acting variants that work together to give rise to a new phenotype. Our lab has pushed the envelope of methods to detect cases of this type of polygenic evolution. In recent published studies we have used Saccharomyces yeast as a test case, and ongoing work is focused on Cryptococcus.
The S. bayanus allele of the GAL1 and GAL10 promoters confers partial rescue of diauxic lag in S. cerevisiae in 1% glucose-galactose medium, from Extended Fig. 2 of Roop et al., 2016
Mapping genotype to phenotype in fungi.
Most fungal genomes are poorly annotated, so we have no idea of the genetic architecture for many fungal traits of industrial and biomedical relevance. In published work, our lab has used variation across wild populations to find the molecular basis of morphology traits in the model fungi Saccharomyces and Neurospora; we have also developed genomic screening approaches to annotate candidate virulence islands in the plant pathogen Zymoseptoria and lipid metabolism genes in the oleaginous yeast Rhodosporidium. Our next project, now in progress, is focused on strain variation in virulence and stress resistance traits in the human pathogen Coccidioides.
Key metabolic pathways and cellular functions mediating lipid metabolism as identified from fitness scores on fatty acid and enrichment scores from lipid accumulation screens. From Figure 6 of Coradetti et al., 2018