Computational study of introgression between Saccharomyces paradoxus and S. cerevisiae

Daniella Corcuera and Justin Fay

Department of Genetics, Washington University School of Medicine

 

Saccharomyces cerevisiae, commonly known as budding or baker’s yeast, has been used extensively in genetic research. Due to its small genome (only around 6,000 functional genes), rapid generation time, and internal structural similarities to other eukaryotes, S. cerevisiae is a model eukaryotic organism for molecular and cell biology. S. cerevisiae has long been associated with humans, as it has been used since ancient times for baking and brewing and is still widely used today. However, geneticists still do not have much knowledge of its evolutionary history, and what makes S. cerevisiae different from its closest relative S. paradoxus. Understanding the differences and similarities between these two species is key to dissecting those traits that make S. cerevisiae so useful.

To begin understanding the similarities and differences between S. cerevisiae and S. paradoxus, the Fay lab has conducted a computational comparison of their genome sequences. Through comparison of the genomic sequences of five S. cerevisiae strains and S. paradoxus, it was found that in certain regions of some of the S. cerevisiae strains, the sequence appears to look more like that of S. paradoxus than that of S. cerevisiae. One explanation for this occurrence is introgression between the species, whereby rare matings between species make it possible for some genes or genomic regions to migrate from one species to another. To identify genes that may have introgressed from S. paradoxus into the S. cerevisiae strains, the lab compiled a list of genes with a high ratio of polymorphism/ divergence (>.5) as well as genome regions that had a high rate of synonymous polymorphism (>3.2%). These regions of high diversity could be the result of introgression or gene conversion, which is the exchange of DNA sequence variation between duplicated sequences within the same genome.

To determine whether regions of high diversity are the result of introgression or gene conversion, I generated multiple sequence alignments and phylogenetic trees for each gene. Using the computer program ClustalW, alignments were created between the sequences of genes within a given region in S. cerevisiae, and the sequences with an identity of at least 85% found in four other strains of S. cerevisiae: YPS163, YJM789, RM11, and M22. The homologs of three other Saccharomyces species— S. paradoxus, S. bayanus, and S. mikatae— were also included in the alignment. A phylogenetic tree was created using the computer program Topali, and bootstrap support for maximum likelihood trees was generated using Phylowin. Using the phylogenetic trees, introgression was distinguished from gene conversion based on whether the S. cerevisiae strains were monophyletic or not.

From the analysis of over sixty genes, approximately 30 genes showed introgression from S. paradoxus into one or more strains of S. cerevisiae. Two notable genes that show evidence of introgression are ENA, which has been mapped to lithium sensitivity, and KRE1, which is a killer toxin membrane receptor. One implication of this introgression is possible cross species adaptation, whereby adaptations that have occurred in one species have spread to another species. The results of the gene sequencing analysis relating to introgression may also further scientific understanding of phenotypic and genotypic variation across the Saccharomyces sensu stricto.