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 1 , mouse 2 , and Arabidopsis thaliana 3 . Here we report a nucleotide-level survey of genome variation in a diverse collection of 63 S. 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 (SNPs), which were grouped into 101,343 distinct segregating sites. We also identified 3,985 deletion events of length >200 bp among the surveyed strains. We analyzed 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.With their small and compact genomes, the hemiascomycetes (the group of fungi that includes S. cerevisiae) represent a powerful model for comparative genomics and studies of genome evolution [4][5][6] . As a result, more than18 hemiascomycetes species are either completely or partially sequenced. The availability of the sequence data has presented an unprecedented opportunity to evaluate DNA sequence variation and genome evolution in a phylum spanning a broad evolutionary range 7 . This wealth of data on interspecific sequence differences stands in contrast to our limited knowledge of sequence variation within S. cerevisiae. Because of its importance both to human activities and as a model system, we sought to generate a comprehensive view of sequence polymorphism in S. cerevisiae. To determine sequence variation at the nucleotide level, we hybridized genomic DNA from 63 ecologically and geographically diverse strains (Table S1) to a high-density Affymetrix Yeast Tiling Microarray (YTM) and identified positions likely to differ from the reference sequence with the software package SNPscanner 8 . We detected a total of 1,896,131 SNPs in nonrepetitive regions of the genome (Table S1). Because of variation of up to a few bp in the location of SNPs detected by SNPscanner, we used a grouping procedure (see Materials and Methods) to identify the sites of polymorphic variation across strains. We also removed all singletons (SNPs called in only one strain) to further reduce false positives. This approach detected a total of 1,299,811 individual SNP calls, which were grouped into 101,343 distinct segregating sites. At each of these sites, every strain was classified as having e...

Genome structure of a Saccharomyces cerevisiae strain widely used in bioethanol production

“…Structural variation, although abundant, was limited to the end sections of chromosomes. A similar pattern has been previously observed in microarray-based surveys of genome variation among different S. cerevisiae strains (Winzeler et al 2003;Carreto et al 2008;Schacherer et al 2009), which found that most polymorphisms, including SNPs and CNVs, were more common within 25 kb of the telomeres. In these studies, however, the full extent of the structural variation in these regions could not be revealed because the microarrays used were based on the S288c genome, and regions of high sequence divergence or sequences that were absent in the reference strain could not be examined.…”

“…Microarray-based whole-genome hybridization studies of wild, industrial, and laboratory S. cerevisiae strains (Winzeler et al 2003;Carreto et al 2008;Faddah et al 2009;Schacherer et al 2009) have uncovered a recurrent pattern of copy number variation (CNV) near the ends of chromosomes, suggesting a role for repetitive DNA sequences in structural genome diversification. Despite these valuable insights, two central questions regarding the role of chromosomal rearrangements in genome evolution in S. cerevisiae remain unanswered: First, it is still unclear how these rearrangements contribute to long-term fitness in natural environments; and second, it is not known if they are compatible with the formation of viable meiotic spores that would allow their sexual dissemination between natural S. cerevisiae populations.…”

“…Extensive analysis has been done to examine the nucleotide sequence diversity between these strains (Liti et al 2009;Schacherer et al 2009), whereas studies of structural variation have mostly focused on comparisons of S. cerevisiae to other related species (Fischer et al 2000;Goffeau 2004;Scannell et al 2007;Gordon et al 2009). Microarray-based whole-genome hybridization studies of wild, industrial, and laboratory S. cerevisiae strains (Winzeler et al 2003;Carreto et al 2008;Faddah et al 2009;Schacherer et al 2009) have uncovered a recurrent pattern of copy number variation (CNV) near the ends of chromosomes, suggesting a role for repetitive DNA sequences in structural genome diversification.…”

Eukaryote-to-eukaryote gene transfer events revealed by the genome sequence of the wine yeast Saccharomyces cerevisiae EC1118

“…These conditions, as well as unwitting selection by man for optimal winemaking traits (fermentation performance, alcohol tolerance, and good flavor production) have generated hundred of strains that are currently used in the wine industry. As a result, wine yeast isolates belong to a well-defined lineage (2)(3)(4)(5)(6).…”

Analysis of the Saccharomyces cerevisiae pan-genome reveals a pool of copy number variants distributed in diverse yeast strains from differing industrial environments

“…Numerous methods have been used to assay genomic variation in yeast and determine relationships between strains, and also used to infer strain origins and history (e.g., Schuller et al 2004;Legras et al 2005). Such studies include comparative analyses of microsatellites (Legras et al 2007;Franco-Duarte et al 2009;Muller and McCusker 2009b;Richards et al 2009), mini-and megasatellites (Richard and Dujon 2006;Rolland et al 2010), copy number variation using aCGH (Pérez-Ortín et al 2002;Infante et al 2003;Winzeler et al 2003;Dunn et al 2005;Carreto et al 2008;Kvitek et al 2008), and polymorphisms detected by tiling arrays (Schacherer et al 2009), as well as the use of multispecies 131-gene taxonomic microarrays (Muller and McCusker 2009a) and Multi Locus Sequence Typing (MLST) (Fay and Benavides 2005a,b;Ayoub et al 2006;Vigentini et al 2009). These studies have mostly shown that yeasts used for a particular industrial use appear to be more closely related, but that geographical migrations, as well as genetic drift, have influenced diversity among S. cerevisiae populations (Legras et al 2007).…”