Baker's yeast, Saccharomyces cerevisiae, is one of the best studied model organisms, and has been associated with human activity for thousands of years. Two papers published in the 19 March 2009 issue of Nature provide a picture of its population structure and its relationship with other yeasts. Liti et al. compare genome variation in S. cerevisiae isolates with its closest wild cousin, S. paradoxus, which has never been associated with human activity. They find that variation in S. paradoxus closely follows geographic borders; S. cerevisiae shows less differentiation, consistent with opportunities for cross-breeding, rather than a few distinct domestication events, as the main human influence. Schacherer et al. compare 63 S. cerevisiae isolates from different ecological niches and geographic locations. They find evidence for genetic differentiation of three distinct subgroups based on where the strains were isolated: from vineyards, sake and related fermentations and lab strains. Their data support the hypothesis that these three groups represent separate domestication events, and that S. cerevisiae as a whole is not domesticated. By sequencing over seventy isolates of the domesticated baker's yeast Saccharomyces cerevisiae and its closest relative, S. paradoxus, this study describes variation in gene content, SNPs, indels, copy numbers and transposable elements, providing insights into the evolution of different lineages, phenotypic variation, domestication and population structure of Saccharomyces. Since the completion of the genome sequence of Saccharomyces cerevisiae in 1996 (refs 1, 2), there has been a large increase in complete genome sequences, accompanied by great advances in our understanding of genome evolution. Although little is known about the natural and life histories of yeasts in the wild, there are an increasing number of studies looking at ecological and geographic distributions3,4, population structure5,6,7,8 and sexual versus asexual reproduction9,10. Less well understood at the whole genome level are the evolutionary processes acting within populations and species that lead to adaptation to different environments, phenotypic differences and reproductive isolation. Here we present one- to fourfold or more coverage of the genome sequences of over seventy isolates of the baker’s yeast S. cerevisiae and its closest relative, Saccharomyces paradoxus. We examine variation in gene content, single nucleotide polymorphisms, nucleotide insertions and deletions, copy numbers and transposable elements. We find that phenotypic variation broadly correlates with global genome-wide phylogenetic relationships. S. paradoxus populations are well delineated along geographic boundaries, whereas the variation among worldwide S. cerevisiae isolates shows less differentiation and is comparable to a single S. paradoxus population. Rather than one or two domestication events leading to the extant baker’s yeasts, the population structure of S. cerevisiae consists of a few well-defined, geographically isolated lineages and many different mosaics of these lineages, supporting the idea that human influence provided the opportunity for cross-breeding and production of new combinations of pre-existing variations.

A fundamental goal in biology is to achieve a mechanistic understanding of how and to what extent ecological variation imposes selection for distinct traits and favors the fixation of specific genetic variants. Key to such an understanding is the detailed mapping of the natural genomic and phenomic space and a bridging of the gap that separates these worlds. Here we chart a high-resolution map of natural trait variation in one of the most important genetic model organisms, the budding yeast Saccharomyces cerevisiae, and its closest wild relatives and trace the genetic basis and timing of major phenotype changing events in its recent history. We show that natural trait variation in S. cerevisiae exceeds that of its relatives, despite limited genetic variation, and follows the population history rather than the source environment. In particular, the West African population is phenotypically unique, with an extreme abundance of low-performance alleles, notably a premature translational termination signal in GAL3 that cause inability to utilize galactose. Our observations suggest that many S. cerevisiae traits may be the consequence of genetic drift rather than selection, in line with the assumption that natural yeast lineages are remnants of recent population bottlenecks. Disconcertingly, the universal type strain S288C was found to be highly atypical, highlighting the danger of extrapolating gene-trait connections obtained in mosaic, lab-domesticated lineages to the species as a whole. Overall, this study represents a step towards an in-depth understanding of the causal relationship between co-variation in ecology, selection pressure, natural traits, molecular mechanism, and alleles in a key model organism. An overall aim in modern biology is to achieve an in-depth understanding of an organism's physiology in the context of its ecology and historic selective pressures that have been acting on its genome. The baker's yeast, Saccharomyces cerevisiae, has a peculiar life history completely dominated by clonal reproduction and self-fertilization, prompting the suggestion that natural yeasts are remnants of repeated population bottlenecks in essentially clonal lineages. Such a life history dominated by mitotic proliferation purports a strong evolutionary influence of genetic drift and predicts trait variation to be high and largely defined by the genetic history of each population. Here we chart a highly resolved map of natural trait variation in S. cerevisiae and its closest non-domesticated relative, Saccharomyces paradoxus, and confirm this prediction. We found that trait variation in budding yeast is indeed high and largely defined by population rather than source environment. In particular, the West African population was found to be phenotypically unique with an extreme abundance of low-performance alleles. Our findings support the idea of population bottlenecks in the recent yeast evolutionary history and a large influence of genetic drift.

Structural rearrangements have long been recognized as an important source of genetic variation, with implications in phenotypic diversity and disease, yet their detailed evolutionary dynamics remain elusive. Here we use long-read sequencing to generate end-to-end genome assemblies for 12 strains representing major subpopulations of the partially domesticated yeastSaccharomyces cerevisiaeand its wild relativeSaccharomyces paradoxus. These population-level high-quality genomes with comprehensive annotation enable precise definition of chromosomal boundaries between cores and subtelomeres and a high-resolution view of evolutionary genome dynamics. In chromosomal cores,S. paradoxusshows faster accumulation of balanced rearrangements (inversions, reciprocal translocations and transpositions), whereasS. cerevisiaeaccumulates unbalanced rearrangements (novel insertions, deletions and duplications) more rapidly. In subtelomeres, both species show extensive interchromosomal reshuffling, with a higher tempo inS. cerevisiae. Such striking contrasts between wild and domesticated yeasts are likely to reflect the influence of human activities on structural genome evolution.

A methodology for large‐scale automated phenotypic profiling utilizing quantitative changes in yeast growth has been tested and applied to the analysis of some commonly used laboratory strains. This yeast‐adjusted methodology is based on microcultivation in 350 µl liquid medium, where growth is frequently optically recorded, followed by automated extraction of relevant variables from obtained growth curves. We report that cultivation at this micro‐scale displayed overall growth features and protein expression pattern highly similar to growth in well aerated medium‐scale (10 ml) culture. However, differences were also encountered, mainly relating to the respiratory potential and the production of stress‐induced proteins. Quantitative phenotypic profiles for the laboratory yeast strains W303, FY1679 and CEN‐PK.2 were screened for in environmental arrays, including 98 different conditions composed of low, medium and high concentrations of 33 growth inhibitors. We introduce the concepts phenotypic index_rate and phenotypic index_stationary, which relate to changes in rate of growth and the stationary phase optical density increment, respectively, in a particular environment relative a reference strain. The laboratory strains presented selective phenotypic profiles in both phenotypic indexes and the two features appeared in many cases to be independent characteristics. We propose the utilization of this methodology in large‐scale screening of the complete collection of yeast deletion mutants. Copyright © 2002 John Wiley & Sons, Ltd.

One approach to understanding the genetic basis of traits is to study their pattern of inheritance among offspring of phenotypically different parents. Previously, such analysis has been limited by low mapping resolution, high labor costs, and large sample size requirements for detecting modest effects. Here, we present a novel approach to map trait loci using artificial selection. First, we generated populations of 10–100 million haploid and diploid segregants by crossing two budding yeast strains of different heat tolerance for up to 12 generations. We then subjected these large segregant pools to heat stress for up to 12 d, enriching for beneficial alleles. Finally, we sequenced total DNA from the pools before and during selection to measure the changes in parental allele frequency. We mapped 21 intervals with significant changes in genetic background in response to selection, which is several times more than found with traditional linkage methods. Nine of these regions contained two or fewer genes, yielding much higher resolution than previous genomic linkage studies. Multiple members of the RAS/cAMP signaling pathway were implicated, along with genes previously not annotated with heat stress response function. Surprisingly, at most selected loci, allele frequencies stopped changing before the end of the selection experiment, but alleles did not become fixed. Furthermore, we were able to detect the same set of trait loci in a population of diploid individuals with similar power and resolution, and observed primarily additive effects, similar to what is seen for complex trait genetics in other diploid organisms such as humans.