Quantitative genetics of natural S. cerevisiae strains upon mating reveal heritable determinants of fitness and differential mating affinities

Among the fundamental questions in sexual reproduction are how fitness is inherited and whether parents exhibit differential mating affinities. Addressing these questions requires quantitative genetic tools and large phenotyped and genotyped strain collections from a single species. We leverage sexual mating among nearly 100 natural isolates of Saccharomyces cerevisiae, generating thousands of offspring across several growth conditions. Using genomic barcodes and a barcode-recombination method to track mating events, we measure fitness for all parents and offspring. In fermentable carbon (glucose), offspring fitness correlates positively, though modestly, with parental fitness. In contrast, in non-fermentable carbon (glycerol), no such correlation is detectable. Instead, offspring fitness in glycerol increases sharply with genetic distance between parents, indicating that outbreeding maximizes fitness independently of parental fitness. Finally, mate affinity varies among parental pairs, with some combinations enriched and others avoided. This work reveals factors shaping fitness inheritance and provides resources for quantitative genetics.