Comprehensive polymorphism survey elucidates population structure of Saccharomyces cerevisiae

Abstract

Comprehensive identification of polymorphisms among individuals within a species is essential both for studying the genetic basis of phenotypic differences and for elucidating the evolutionary history of the species. Large-scale polymorphism surveys have recently been reported for human, mouse and Arabidopsis thaliana. Here we report a nucleotide-level survey of genomic variation in a diverse collection of 63 Saccharomyces cerevisiae strains sampled from different ecological niches (beer, bread, vineyards, immunocompromised individuals, various fermentations and nature) and from locations on different continents. We hybridized genomic DNA from each strain to whole-genome tiling microarrays and detected 1.89 million single nucleotide polymorphisms, which were grouped into 101,343 distinct segregating sites. We also identified 3,985 deletion events of length >200 base pairs among the surveyed strains. We analysed the genome-wide patterns of nucleotide polymorphism and deletion variants, and measured the extent of linkage disequilibrium in S. cerevisiae. These results and the polymorphism resource we have generated lay the foundation for genome-wide association studies in yeast. We also examined the population structure of S. cerevisiae, providing support for multiple domestication events as well as insight into the origins of pathogenic strains.

Figure 1

Decay of linkage disequilibrium as a function of distance. Averages of pairwise LD measures r² (black circles) and D' (open circles) are plotted for each bin of distances between pairs of SNPs. The LD values were corrected for finite-size effects by subtracting the average value computed for a random subset of pairs of SNPs located on different chromosomes.

Figure 2

Neighbor-joining tree of 63 Saccharomyces cerevisiae strains. The tree was constructed based on the 101,343 segregating sites identified in the surveyed strains. Branch lengths are proportional to the number of the 101,343 segregating sites that differentiate each pair of strains. Font color of strain name denotes geographic origin and circle color denotes ecological niche as specified in the key.

Figure 3

Population structure of 63 Saccharomyces cerevisiae strains. Cluster results from a structure analysis on 101,343 segregating sites identified in the 63 surveyed strains. Structure implements a Bayesian model-based clustering algorithm that attempts to identify genetically distinct subpopulations based on patterns of allele frequencies. Each strain is represented by a single vertical bar, which is partitioned into K colored segments that represent the strain’s estimated ancestry proportion in each of the K clusters.