Maltotriose consumption by hybrid Saccharomyces pastorianus is heterotic and results from regulatory cross-talk between parental sub-genomes

strains are hybrids of and that have been domesticated for several centuries in lager-beer brewing environments. As sequences and structures of genomes are being resolved, molecular mechanisms and evolutionary origin of several industrially relevant phenotypes remain unknown. This study investigates how maltotriose metabolism, a key feature in brewing, may have arisen in early hybrids. To address this question, we generated a near-complete genome assembly of Himalayan strains of the Holarctic subclade. This group of strains have been proposed to be the origin of the subgenome of current strains. The Himalayan genomes harbored several copies of a α-oligoglucoside transporter gene with high sequence identity to genes encountered in . Although Himalayan strains are unable to grown on maltose and maltotriose, their maltose-hydrolase and and maltose-transporter genes complemented the corresponding null mutants of . Expression, in a Himalayan strain, of a functional maltose-metabolism regulator gene () enabled growth on oligoglucosides. The hypothesis that the maltotriose-positive phenotype in is a result of heterosis was experimentally tested by constructing a × laboratory hybrid with a complement of maltose-metabolism genes that resembles that of current strains. The ability of this hybrid to consume maltotriose in brewer’s wort demonstrated regulatory cross talk between sub-genomes and thereby validated this hypothesis. These results provide experimental evidence of the evolutionary origin of an essential phenotype of lager-brewing strains and valuable knowledge for industrial exploitation of laboratory-made -like hybrids.