Population genomic analysis of outcrossing and recombination in yeast

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The budding yeast Saccharomyces cerevisiae has been used by humans for millennia to make wine, beer and bread1. More recently, it became a key model organism for studies of eukaryotic biology and for genomic analysis2. However, relatively little is known about the natural lifestyle and population genetics of yeast3. One major question is whether genetically diverse yeast strains mate and recombine in the wild. We developed a method to infer the evolutionary history of a species from genome sequences of multiple individuals and applied it to whole-genome sequence data from three strains of Saccharomyces cerevisiae2,4 and the sister species Saccharomyces paradoxus5. We observed a pattern of sequence variation among yeast strains in which ancestral recombination events lead to a mosaic of segments with shared genealogy. Based on sequence divergence and the inferred median size of shared segments (2,000 bp), we estimated that although any two strains have undergone approximately 16 million cell divisions since their last common ancestor, only 314 outcrossing events have occurred during this time (roughly one every 50,000 divisions). Local correlations in polymorphism rates indicate that linkage disequilibrium in yeast should extend over kilobases. Our results provide the initial foundation for population studies of association between genotype and phenotype in S. cerevisiae.

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Figure 1: Inference of ancestral recombination from tree-diagnostic SNPs.
Figure 2: Cumulative distribution of the length of shared ancestral segments.
Figure 3: Coalescent simulations of median shared segment lengths as a function of population recombination parameter R.
Figure 4: Correlation in polymorphism as a function of distance, corrected for stochastic variance (Methods).


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We thank D. Botstein, R. Brem, H. Coller, J. Ronald and especially M. Rockman for helpful discussions and comments on the manuscript. We thank the Broad Institute Fungal Genome Initiative, led by B. Birren, for generating the sequences of RM11-1a and S. paradoxus, and the Stanford Genome Technology Center, especially L. Steinmetz and R. Davis, for generating the sequence of YJM789. This work was supported by US National Institute of Mental Health grant R37 MH059520 and a James S. McDonnell Foundation Centennial Fellowship. SCP is supported by a grant from the Pew Charitable Trusts (award 2000-002558).

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Correspondence to Leonid Kruglyak.

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Ruderfer, D., Pratt, S., Seidel, H. et al. Population genomic analysis of outcrossing and recombination in yeast. Nat Genet 38, 1077–1081 (2006) doi:10.1038/ng1859

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