PT - JOURNAL ARTICLE AU - Zebin Zhang AU - Devin P. Bendixsen AU - Thijs Janzen AU - Arne W. Nolte AU - Duncan Greig AU - Rike Stelkens TI - Recombining your way out of trouble: The genetic architecture of hybrid fitness under environmental stress AID - 10.1101/622845 DP - 2019 Jan 01 TA - bioRxiv PG - 622845 4099 - http://biorxiv.org/content/early/2019/04/30/622845.short 4100 - http://biorxiv.org/content/early/2019/04/30/622845.full AB - Hybridization between species is a fundamental evolutionary force that can both promote and delay adaptation. There is a deficit in our understanding of the genetic basis of hybrid fitness, especially in non-domesticated organisms. We also know little about how hybrid fitness changes as a function of environmental stress. Here, we made genetically variable F2 hybrid populations from two divergent Saccharomyces yeast species, exposed populations to ten toxins, and sequenced the most resilient hybrids on low coverage using ddRADseq. We expected to find strong negative epistasis and heterozygote advantage in the hybrid genomes. We investigated three aspects of hybridness: 1) hybridity, 2) interspecific heterozygosity, and 3) epistasis (positive or negative associations between non-homologous chromosomes). Linear mixed effect models revealed strong genotype-by-environment interactions with many chromosomes and chromosomal interactions showing species-biased content depending on the environment. Against our predictions, we found extensive selection against heterozygosity such that homozygous allelic combinations from the same species were strongly overrepresented in an otherwise hybrid genomic background. We also observed multiple cases of positive epistasis between chromosomes from opposite species, confirmed by epistasis- and selection-free simulations, which is surprising given the large divergence of the parental species (~15% genome-wide). Together, these results suggest that stress-resilient hybrid genomes can be assembled from the best features of both parents, without paying high costs of negative epistasis across large evolutionary distances. Our findings illustrate the importance of measuring genetic trait architecture in an environmental context when determining the evolutionary potential of hybrid populations.