An Out-of-Patagonia migration explains the worldwide diversity and distribution of Saccharomyces eubayanus lineages

Author summary Lager yeast history has intrigued scientists for decades. The recent isolation of S. eubayanus, the lager yeast ancestor, represents an unprecedented opportunity to extend our knowledge on yeast phylogeography and the origins of the S. pastorianus lager hybrid. However, the genetic, phenotypic and evolutionary history of this species remains poorly known. Our work demonstrates that S. eubayanus isolates from Patagonia have the greatest genetic diversity, comprising the largest number of lineages within a single geographic region and experienced ancestral and recent admixture between lineages, likely suggesting co-occurrence in Patagonia. Importantly, some isolates exhibited significant phenotypic differences for traits such as high temperature and ethanol tolerance, together with fermentation performance, demonstrating their potential in the brewing industry for the generation of new styles of lager beers. Furthermore, our results support the idea of colonization from peripheral glacial refugia from the South, as responsible for the high genetic diversity observed in southern Chilean Patagonia. Our results allow hypothesizing a successful physiological adjustment of the species to the local conditions in Patagonia, explaining its wide distribution in the southern hemisphere. Population-level sampling and whole-genome sequences of different individuals allow one to identify signatures of hybridization, gene flow and potential molecular mechanisms of environmental responses. Here, we report the isolation of 160 Saccharomyces eubayanus strains, the cryotolerant ancestor of lager yeast, from ten sampling sites in Patagonia along 2,000 km of Nothofagus forests. Frequency of S. eubayanus isolates was higher towards southern and colder regions, demonstrating the cryotolerant nature of the species. We sequenced the genome of 82 strains and, together with 23 available genomes, performed a comprehensive phylogenetic analysis. Our results revealed the presence of five different lineages together with dozens of admixed strains. Various analytical methods reveal evidence of gene flow and historical admixture between lineages from Patagonia and Holarctic regions, suggesting the co-occurrence of these ancestral populations. Analysis of the genetic contribution to the admixed genomes revealed a Patagonian genetic origin of the admixed strains, even for those located in the North Hemisphere. Overall, the Patagonian lineages, particularly the southern populations, showed a greater global genetic diversity compared to Holarctic and Chinese lineages, in agreement with a higher abundance in Patagonia. Thus, our results are consistent with a likely colonization of the species from peripheral glacial refugia from South Patagonia. Furthermore, fermentative capacity and maltose consumption resulted negatively correlated with latitude, indicating better fermentative performance in northern populations. Our genome analysis, together with previous reports in the sister species S. uvarum suggests that a S. eubayanus ancestor was adapted to the harsh environmental conditions of Patagonia, a region that provides the ecological conditions for the diversification of these ancestral lineages.