PT  - JOURNAL ARTICLE
AU  - Alex N. Salazar
AU  - Arthur R. Gorter de Vries
AU  - Marcel van den Broek
AU  - Nick Brouwers
AU  - Pilar de la Torre Cortès
AU  - Niels G. A Kuijpers
AU  - Jean-Marc G. Daran
AU  - Thomas Abeel
TI  - Nanopore sequencing and comparative genome analysis confirm lager-brewing yeasts originated from a single hybridization
AID  - 10.1101/603480
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 603480
4099  - http://biorxiv.org/content/early/2019/04/09/603480.short
4100  - http://biorxiv.org/content/early/2019/04/09/603480.full
AB  - Background The lager brewing yeast, S. pastorianus, is a hybrid between S. cerevisiae and S. eubayanus with extensive chromosome aneuploidy. S. pastorianus is subdivided into Group 1 and Group 2 strains, where Group 2 strains have higher copy number and a larger degree of heterozygosity for S. cerevisiae chromosomes. As a result, Group 2 strains were hypothesized to have emerged from a hybridization event distinct from Group 1 strains. Current genome assemblies of S. pastorianus strains are incomplete and highly fragmented, limiting our ability to investigate their evolutionary history.Results To fill this gap, we generated a chromosome-level genome assembly of the S. pastorianus strain CBS 1483 using MinION sequencing and analysed the newly assembled subtelomeric regions and chromosome heterozygosity. To analyse the evolutionary history of S. pastorianus strains, we developed Alpaca: a method to compute sequence similarity between genomes without assuming linear evolution. Alpaca revealed high similarities between the S. cerevisiae subgenomes of Group 1 and 2 strains, and marked differences from sequenced S. cerevisiae strains.Conclusions Our findings suggest that Group 1 and Group 2 strains originated from a single hybridization involving a heterozygous S. cerevisiae strain, followed by different evolutionary trajectories. The clear differences between both groups may originate from a severe population bottleneck caused by the isolation of the first pure cultures. Alpaca provides a computationally inexpensive method to analyse evolutionary relationships while considering non-linear evolution such as horizontal gene transfer and sexual reproduction, providing a complementary viewpoint beyond traditional phylogenetic approaches.