Heterosis, also known as hybrid vigor, is the superior performance of a heterozygous hybrid relative to its homozygous parents. Despite the scientific curiosity of this phenotypic phenomenon and its significance for food production in agriculture, its genetic basis is insufficiently understood. Studying heterosis in yeast can potentially yield insights into its genetic basis, can allow one to test the different hypotheses that have been proposed to explain the phenomenon and allows better understanding of how to take advantage of this phenomenon to enhance food production. We therefore crossed 16 parental yeast strains to form 120 yeast hybrids, and measured their growth rates under five environmental conditions. A considerable amount of dominant genetic variation was found in growth performance, and heterosis was measured in 35% of the hybrid-condition combinations. Despite previous reports of correlations between heterosis and measures of sequence divergence between parents, we detected no such relationship. We used several analyses to examine which genetic model might explain heterosis. We found that dominance complementation of recessive alleles, overdominant interactions within loci and epistatic interactions among loci each contribute to heterosis. We concluded that in yeast heterosis is a complex phenotype created by the combined contribution of different genetic interactions.

Heterosis describes a phenotypic phenomenon of hybrid superiority over its homozygous parents. It is a genetically intriguing phenomenon with great importance for food production. Also called hybrid-vigor, heterosis is created by non-additive effects of genes in a heterozygous hybrid made by crossing two distinct homozygous parents. Few models have been proposed to explain how the combination of parental genes creates an exceptional hybrid performance. Over-dominant mode of inheritance is an attractive model since a single gene can potentially create the heterotic effect, but only a few such loci have been identified. To a collection of 120 hybrids, made by crossing 16 divergent Saccharomyces cerevisiae yeast strains, we applied a method for mapping heterozygous loci that non-additively contribute to heterotic growth at 37°. Among 803 candidate loci that were mapped, five were tested for their heterotic effect by analyzing backcrosses and F2 populations in a specific hybrid background. Consistently with the many mapped loci, specific analyses confirmed the minor heterotic effect of the tested candidate loci. Allele-replacement analyses of one gene, AEP3, further supported its heterotic effect. In addition to over-dominant effects, the contribution of epistasis to heterosis was evident from F2 population and allele-replacement analyses. Pairs of over-dominant genes contributed synergistically to heterosis. We show that minor over-dominant effects of multiple genes can combine to condition heterosis, similarly to loci affecting other quantitative traits. Furthermore, by finding of epistatic interactions between loci that each of them individually has an over-dominant effect on heterosis, we demonstrate how hybrid advantage could benefit from a synergistic combination of two interaction types (over-dominant and synergistic epistatic). Thus, by portraying the underlying genetic complexity, these findings advance our understanding of heterosis.