The Genetic Basis of Natural Variation in Oenological Traits in Saccharomyces cerevisiae

Salinas, F.; Cubillos, Francisco A.; Soto, Daniela; García, Verónica; Bergström, Anders; Warringer, Jonas; Ganga, María Angélica; Louis, Edward J.; Liti, Gianni; Martı́nez, Claudio

doi:10.1371/journal.pone.0049640

Cited by 70 publications

(81 citation statements)

References 62 publications

(102 reference statements)

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“…We used the DBVPG6765 strain as representative of the WE lineage, YPS128 of the NA lineage, Y12 of the SA lineage, and DBVPG6044 of the WA one. These strains have been extensively characterized at the genomic (Liti et al 2009a) and phenotypic ) levels and successfully used for QTL mapping in two-parent crosses Parts et al 2011;Salinas et al 2012). To further improve the reference genomes, we resequenced the founders at high coverage and generated high-quality assemblies, containing .95% of the sequence for each strain in one large scaffold per chromosome (A. Bergström, J. T. Simpson, F. Salinas, L. Parts, A. Zia, A. N. Nguyen Ba, A. M. Moses, E. J. Louis, V. Mustonen, J. Warringer, R. Durbin, and G. Liti, unpublished results).…”

Section: Genetic Background Of Founder Strainsmentioning

confidence: 99%

High-Resolution Mapping of Complex Traits with a Four-Parent Advanced Intercross Yeast Population

et al. 2013

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A large fraction of human complex trait heritability is due to a high number of variants with small marginal effects and their interactions with genotype and environment. Such alleles are more easily studied in model organisms, where environment, genetic makeup, and allele frequencies can be controlled. Here, we examine the effect of natural genetic variation on heritable traits in a very large pool of baker's yeast from a multiparent 12th generation intercross. We selected four representative founder strains to produce the Saccharomyces Genome Resequencing Project (SGRP)-4X mapping population and sequenced 192 segregants to generate an accurate genetic map. Using these individuals, we mapped 25 loci linked to growth traits under heat stress, arsenite, and paraquat, the majority of which were best explained by a diverging phenotype caused by a single allele in one condition. By sequencing pooled DNA from millions of segregants grown under heat stress, we further identified 34 and 39 regions selected in haploid and diploid pools, respectively, with most of the selection against a single allele. While the most parsimonious model for the majority of loci mapped using either approach was the effect of an allele private to one founder, we could validate examples of pleiotropic effects and complex allelic series at a locus. SGRP-4X is a deeply characterized resource that provides a framework for powerful and high-resolution genetic analysis of yeast phenotypes and serves as a test bed for testing avenues to attack human complex traits.T HE strong tendency for progeny to closely resemble their parents has turned out to be difficult to understand in detail. Nearly all traits, including lifetime risk for many common diseases, have a complex genetic basis that is determined by multiple quantitative trait loci (QTL) (Donnelly 2008;Manolio et al. 2009). The first step toward accurate models of trait variability, and a prerequisite for predicting and modulating them, is characterization of the underlying genetic factors in the context of rest of the genome and their external environment. Research in model systems has led the way in this effort and produced powerful experimental and computational approaches for genetic mapping (Nordborg and Weigel 2008;Flint and Mackay 2009;Mackay et al. 2009).A traditional, well-controlled approach for finding the QTL underlying natural phenotypic variation is to analyze a large number of progenies from two-parent crosses (Brem et al. 2002;Simon et al. 2008). Studies using this design have improved our understanding of complex traits and provided concrete evidence of natural segregating variants ), but have been limited in their scope with regard to the extent of genetic variation between the two parents. Mapping populations of popular model organisms ranging from fruit flies (King et al. 2012) (Churchill et al. 2004;Durrant et al. 2011) to plants (Kover et al. 2009;Gan et al. 2011;Huang et al. 2011) has recently expanded the genetic and phenotypic diversity available to study by ...

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Section: Genetic Background Of Founder Strainsmentioning

confidence: 99%

High-Resolution Mapping of Complex Traits with a Four-Parent Advanced Intercross Yeast Population

et al. 2013

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“…For polygenic traits, it is called heterosis. Heterosis is commonly associated to macroscopic traits, but it also applies to less integrated traits such as metabolite abundances (3,4), fluxes and enzyme activities (5-7), mRNA, and protein amounts (8).…”

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A Systems Approach to Elucidate Heterosis of Protein Abundances in Yeast

Blein-Nicolas

Albertin

Silva

et al. 2015

Molecular & Cellular Proteomics

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Heterosis is a universal phenomenon that has major implications in evolution and is of tremendous agro-economic value. To study the molecular manifestations of heterosis and to find factors that maximize its strength, we implemented a large-scale proteomic experiment in yeast. We analyzed the inheritance of 1,396 proteins in 55 inter-and intraspecific hybrids obtained from Saccharomyces cerevisiae and S. uvarum that were grown in grape juice at two temperatures. We showed that the proportion of heterotic proteins was highly variable depending on the parental strain and on the temperature considered. For intraspecific hybrids, this proportion was higher at nonoptimal temperature. Unexpectedly, heterosis for protein abundance was strongly biased toward positive values in interspecific hybrids but not in intraspecific hybrids. Computer modeling showed that this observation could be accounted for by assuming concave relationships between protein abundances and their controlling factors, in line with the metabolic model of heterosis. These results point to nonlinear processes that could play a central role in heterosis. Molecular & Cellular

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“…cerevisiae has also been a focus for studies of natural genetic variation and polygenic traits (Liti and Louis 2012), as strains found in nature display a broad range of phenotypic variance (Ehrenreich et al 2009;Liti and Louis 2012). Studies of yeast strain natural variance have identified the causative alleles for a number of polygenic traits including sporulation efficiency (Deutschbauer and Davis 2005;Ben-Ari et al 2006;Gerke et al 2006), high temperature growth (Steinmetz et al 2002), translation efficiency (Torabi and Kruglyak 2011), and wine alcoholic fermentation (Salinas et al 2012). A major advantage of yeast in studies of natural variation caused by multiple mutations is the ability to perform allele replacements, allowing direct tests for causative mutations.…”

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Analysis of Polygenic Mutants Suggests a Role for Mediator in Regulating Transcriptional Activation Distance in Saccharomyces cerevisiae

et al. 2015

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Studies of natural populations of many organisms have shown that traits are often complex, caused by contributions of mutations in multiple genes. In contrast, genetic studies in the laboratory primarily focus on studying the phenotypes caused by mutations in a single gene. However, the single mutation approach may be limited with respect to the breadth and degree of new phenotypes that can be found. We have taken the approach of isolating complex, or polygenic mutants in the lab to study the regulation of transcriptional activation distance in yeast. While most aspects of eukaryotic transcription are conserved from yeast to human, transcriptional activation distance is not. In Saccharomyces cerevisiae, the upstream activating sequence (UAS) is generally found within 450 base pairs of the transcription start site (TSS) and when the UAS is moved too far away, activation no longer occurs. In contrast, metazoan enhancers can activate from as far as several hundred kilobases from the TSS. Previously, we identified single mutations that allow transcription activation to occur at a greater-than-normal distance from the GAL1 UAS. As the single mutant phenotypes were weak, we have now isolated polygenic mutants that possess strong long-distance phenotypes. By identification of the causative mutations we have accounted for most of the heritability of the phenotype in each strain and have provided evidence that the Mediator coactivator complex plays both positive and negative roles in the regulation of transcription activation distance. KEYWORDS transcription; Mediator; polygenic; Saccharomyces cerevisiae T HE correct communication between a transcriptional activator and its target gene is of crucial importance to ensure properly regulated transcription. While most fundamental aspects of transcription initiation are conserved throughout eukaryotes, the distance over which transcriptional activation can occur varies greatly between yeast and metazoans. In the compact Saccharomyces cerevisiae genome, where intergenic distances are small and upstream activation sequences (UASs) are generally found within 450 base pairs (bp) of the transcription start site (Goffeau et al. 1996;Kristiansson et al. 2009), it is important that activation occurs over only a short distance to activate the correct target gene. In contrast, in the much larger metazoan genomes, enhancers that activate transcription are often located several kilobases away, with some enhancers as far as a megabase from a target gene (Bulger and Groudine 2011;Buecker and Wysocka 2012;Erokhin et al. 2015). While many studies have focused on understanding how enhancers function over a long distance to choose the correct target (Krivega and Dean 2012), there is less understanding of the regulation of transcriptional activation distance in yeast and how it differs from that in metazoans.Early studies of yeast UAS elements suggested that transcriptional activation distance is limited (Guarente and Hoar 1984;Struhl 1984). More recent work systematically measured the...

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The Genetic Basis of Natural Variation in Oenological Traits in Saccharomyces cerevisiae

Cited by 70 publications

References 62 publications

High-Resolution Mapping of Complex Traits with a Four-Parent Advanced Intercross Yeast Population

High-Resolution Mapping of Complex Traits with a Four-Parent Advanced Intercross Yeast Population

A Systems Approach to Elucidate Heterosis of Protein Abundances in Yeast

Analysis of Polygenic Mutants Suggests a Role for Mediator in Regulating Transcriptional Activation Distance in Saccharomyces cerevisiae

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