Skip to main content
Premium Trial:

Request an Annual Quote

Researchers Track Genotype Evolution of Saccharomyces Cerevisiae Isolates

NEW YORK (GenomeWeb) – As part of a flagship project begun by France Génomique, an international team of researchers has generated a detailed map of genetic evolution in Saccharomyces cerevisiae, allowing the group to better understand the population-level natural genetic and phenotypic diversity of eukaryote model systems.

In a study published in Nature today, the researchers sequenced strains from around the world in order to provide as much global and ecological diversity as possible, then phenotyped and determined the isolates' growth fitness in different conditions that impacted various physiological and cellular responses. They found a total of 1,625,809 high-quality reference-based SNPs, most of which were detected at a very low frequency.

In order to investigate ancestry in the genomes of individual strains, the team used a subset of highly contiguous de novo assemblies that sampled the main S. cerevisiae lineages and closely related species to generate a rooted phylogenetic tree.

The genomic analysis indicated evidence of East Asian origin and strongly suggested that S. cerevisiae began to disperse through the world from a single out-of-China event. The study noted that due to human activity, S. cerevisiae underwent genomic and phenotypic changes during multiple and independent domestication events linked to human processes — such as wine, sake, and beer fermentation.

Because 217 strains were genetically manipulated and no longer in their natural ploidy states, the team assigned relative ploidy states to 794 isolates and found nine haploids, 694 diploids, and 91 isolates with higher ploidy. The results revealed that around 87 percent of the natural isolates were in a diploid state.

By testing the effect of ploidy on growth fitness across the species, the team noticed that diploid states had a general advantage compared to other types of ploidy. The team's results support a mitotic growth advantage for diploidy in yeast that held across every condition tested and did not demonstrate major environment-specific effects.

The researchers observed a total of 342 cases of aneuploidy that affected 193 isolates, involving chromosomes I, III, and IX. They also noted a strong enrichment of aneuploid strains in the sake, ale beer, and mixed-origin clades, indicating that aneuploidy is both common and yet has a paradoxical relationship with fitness. In addition, the team found a general mitotic growth advantage in euploid versus aneuploid strains, consistent with a fitness cost for chromosomal aneuploidy.

Within the S. cerevisiae pangenome, the team identified 4,940 core original reading frames (ORFs) present in all 1,011 sequenced strains, as well as 2,856 ORFs that are variable within the population. Most core ORFS were present as a single copy per haploid genome, while variable ORFs showed a higher frequency of both homozygous and multi-allelic copy numbers.

Analyzing the 6,081 non-redundant ORFs in a well-annotated reference genome, the team identified different trends within the core genome. This includes a bias of variable ORF distribution toward subtelomeric regions, as well as a characterization of lower levels of loss-of-function mutations and a different ratio of substitution rates.

In order to trace the origins of variable ORFs, the team inspected the evolution of each individual ORF. Defining 1,380 ancestral segregating ORFs with sequencing-similarity levels, the researchers identified 913 introgressed ORFs linked to a Saccharomyces paradoxus origin. In addition, they saw that 183 ORFS were likely caused by horizontal gene transfer in highly divergent yeast species, but were restricted to species present in domestic fermentative environments.

While domesticated isolates exhibited high variation in ploidy, aneuploidy, and genome content, the researchers believe that genome evolution in wild isolates occurred through addition of single nucleotide polymorphisms.

The team also found that S. cerevisiae specimens shared an extensive loss of heterozygosity, indicating a source of inter-individual variation in the mostly asexual species.

"Overall, our data support[s] that S. cerevisiae undergoes clonal expansion followed by LOH-mediated diversification, enabling the expression of recessive alleles and generating novel allele combinations with potential effects on phenotypic diversity," the authors noted.

The researchers found that among the 1,011 genomes, there was higher SNP density and lower genome content frequency in wild versus domesticated clades. The largest numbers of variants identified by genome-wide association included copy-number changes, which have a greater effect on phenotype than SNPs.

The team noted that the study has established the foundation for genome-wide association studies in S. cerevisiae. In addition, the study revealed a previously undescribed evolutionary history as well as the driving forces of genome evolution for the yeast species. They believe that the collection of genetic and phenotypic variants will will guide future population genomics and genotype-phenotype studies.