High-quality, well-annotated genome sequences and standardized laboratory strains fuel experimental and evolutionary research. We present improved genome sequences of three species of Saccharomyces sensu stricto yeasts: S. bayanus var. uvarum (CBS 7001), S. kudriavzevii (IFO 1802T and ZP 591), and S. mikatae (IFO 1815T), and describe their comparison to the genomes of S. cerevisiae and S. paradoxus. The new sequences, derived by assembling millions of short DNA sequence reads together with previously published Sanger shotgun reads, have vastly greater long-range continuity and far fewer gaps than the previously available genome sequences. New gene predictions defined a set of 5261 protein-coding orthologs across the five most commonly studied Saccharomyces yeasts, enabling a re-examination of the tempo and mode of yeast gene evolution and improved inferences of species-specific gains and losses. To facilitate experimental investigations, we generated genetically marked, stable haploid strains for all three of these Saccharomyces species. These nearly complete genome sequences and the collection of genetically marked strains provide a valuable toolset for comparative studies of gene function, metabolism, and evolution, and render Saccharomyces sensu stricto the most experimentally tractable model genus. These resources are freely available and accessible through www.SaccharomycesSensuStricto.org.

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Among yeasts that underwent whole-genome duplication (WGD), Kluyveromyces polysporus represents the lineage most distant from Saccharomyces cerevisiae. By sequencing the K. polysporus genome and comparing it with the S. cerevisiae genome using a likelihood model of gene loss, we show that these species diverged very soon after the WGD, when their common ancestor contained >9,000 genes. The two genomes subsequently converged onto similar current sizes (5,600 protein-coding genes each) and independently retained sets of duplicated genes that are strikingly similar. Almost half of their surviving single-copy genes are not orthologs but paralogs formed by WGD, as would be expected if most gene pairs were resolved independently. In addition, by comparing the pattern of gene loss among K. polysporus, S. cerevisiae, and three other yeasts that diverged after the WGD, we show that the patterns of gene loss changed over time. Initially, both members of a duplicate pair were equally likely to be lost, but loss of the same gene copy in independent lineages was increasingly favored at later time points. This trend parallels an increasing restriction of reciprocal gene loss to more slowly evolving gene pairs over time and suggests that, as duplicate genes diverged, one gene copy became favored over the other. The apparent low initial sequence divergence of the gene pairs leads us to propose that the yeast WGD was probably an autopolyploidization.genomics ͉ polyploidy ͉ reciprocal gene loss ͉ Vanderwaltozyma polyspora A n ancestor of Saccharomyces cerevisiae underwent wholegenome duplication (WGD) after it had diverged from non-WGD yeast lineages such as Kluyveromyces lactis, Kluyveromyces waltii, and Ashbya gossypii (1-4). The WGD had a major impact on the evolution of S. cerevisiae and its relatives, most notably by facilitating their adaptation to anaerobic growth (5) and contributing to their rapid speciation (6). In S. cerevisiae, Ϸ20% of genes are members of duplicated pairs that were formed in the WGD (7). The other loci became single-copy again during the sorting-out process (genome reduction) that occurred after the WGD. Similar large-scale loss of copies of duplicated genes from paleopolyploid genomes has occurred during the evolution of plants such as grasses and crucifers (8-11).Because the S. cerevisiae genome sequence is a single observation of the evolutionary result of the WGD that occurred in a yeast ancestor, it has not been clear whether the set of genes that survived the sorting-out process in S. cerevisiae was an inevitable outcome of the WGD, or whether stochastic processes played a major role. Two questions need to be answered. First, are the loci that remain duplicated in S. cerevisiae a special subset of the pre-WGD genome, that were somehow more amenable to retention in duplicate after WGD? Second, for loci that are now single-copy in S. cerevisiae, was retention of one particular gene copy preferred over the other? These questions are best addressed by studying the genomes of other yeast species tha...

Summary Deciphering the molecular basis of pluripotency is fundamental to our understanding of development and embryonic stem cell function. Here we report that TAF3, a TBP-associated core promoter factor, is highly enriched in ES cells. TAF3 is required for endoderm lineage differentiation and prevents premature specification of neuroectoderm and mesoderm. In addition to its role in the core promoter recognition complex TFIID, genome-wide binding studies reveal that TAF3 localizes to chromosomal regions bound by CTCF and cohesin. Enrichment for TAF3/CTCF/cohesin bound regions distinguishes TAF3-activated from TAF3-repressed genes. Notably, CTCF directly interacts with and recruits TAF3 to promoter distal sites and TAF3-dependent DNA looping is observed between the promoter distal sites and core promoters occupied by TAF3/CTCF/cohesin. Thus, our findings support a new role of TAF3 in mediating long-range chromatin regulatory interactions to safeguard the finely-balanced transcriptional programs that give rise to pluripotency.