Gu, Z. et al. Elevated evolutionary rates in the laboratory strain of Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 102, 1092-1097

Stanford Genome Technology Center, 855 California Avenue, Palo Alto, CA 94304, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/2005; 102(4):1092-7. DOI: 10.1073/pnas.0409159102
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By using the maximum likelihood method, we made a genome-wide comparison of the evolutionary rates in the lineages leading to the laboratory strain (S288c) and a wild strain (YJM789) of Saccharomyces cerevisiae and found that genes in the laboratory strain tend to evolve faster than in the wild strain. The pattern of elevated evolution suggests that relaxation of selection intensity is the dominant underlying reason, which is consistent with recurrent bottlenecks in the S. cerevisiae laboratory strain population. Supporting this conclusion are the following observations: (i) the increases in nonsynonymous evolutionary rate occur for genes in all functional categories; (ii) most of the synonymous evolutionary rate increases in S288c occur in genes with strong codon usage bias; (iii) genes under stronger negative selection have a larger increase in nonsynonymous evolutionary rate; and (iv) more genes with adaptive evolution were detected in the laboratory strain, but they do not account for the majority of the increased evolution. The present discoveries suggest that experimental and possible industrial manipulations of the laboratory strain of yeast could have had a strong effect on the genetic makeup of this model organism. Furthermore, they imply an evolution of laboratory model organisms away from their wild counterparts, questioning the relevancy of the models especially when extensive laboratory cultivation has occurred. In addition, these results shed light on the evolution of livestock and crop species that have been under human domestication for years.

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    • "In addition to the shuffling of allele frequencies , decrease in population size could lead to the accumulation of slightly deleterious mutations (Ohta 1992). Such an accumulation has been detected by an increase in nonsynonymous (amino acid changing) over synonymous (amino acid conservative) substitutions in dog (Bj€ ornerfeldt et al. 2006; Cruz et al. 2008), laboratory yeast (Gu et al. 2005) and yak (Wang et al. 2011) but also potentially in Asian rice (Lu et al. 2006). Beside demography , other genomic features including recombination rates and genetic linkage to selected sites are known to influence neutral polymorphism levels (Cutter & Payseur 2013). "
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    ABSTRACT: The African cultivated rice (Oryza glaberrima) was domesticated in West Africa 3,000 years ago. Although less cultivated than the Asian rice (O. sativa), O. glaberrima landraces often display interesting adaptation to rustic environment (e.g., drought). Here, using RNA-seq technology we were able to compare more than 12,000 transcripts between 9 O. glaberrima, 10 wild O. barthii and one O. meridionalis individuals. With a synonymous nucleotide diversity πs = 0.0006 per site, O. glaberrima appears as the least genetically diverse crop grass ever documented. Using Approximate Bayesian Computation, we estimated that O. glaberrima experienced a severe bottleneck during domestication. This demographic scenario almost fully accounts for the pattern of genetic diversity across O. glaberrima genome as we detected very few outliers regions where positive selection may have further impacted genetic diversity. Moreover, the large excess of derived non-synonymous substitution that we detected suggests that the O. glaberrima population suffered from the “cost of domestication”. In addition, we used this genome-scale dataset to demonstrate that (i) O. barthii genetic diversity is positively correlated with recombination rate and negatively with gene density; (ii) expression level is negatively correlated with evolutionary constraint and (iii) one region on chromosome 5 (position 4-6 Mb) exhibits a clear signature of introgression with a yet unidentified Oryza species. This work represents the first genome-wide survey of the African rice genetic diversity and paves the way for further comparison between the African and the Asian rice, notably regarding the genetics underlying domestication traits.This article is protected by copyright. All rights reserved.
    Molecular Ecology 03/2014; 23(9). DOI:10.1111/mec.12738 · 6.49 Impact Factor
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    • "In conclusion, we demonstrate that variation in an important TF is responsible for major phenotypic changes in yeast. Previous studies have highlighted the elevated levels of nonsynonymous changes in TFs among different yeast strains (Gu et al. 2005). Since many human TFs and other regulatory proteins are also polymorphic, it is likely that some of these potential master variators may also be responsible for phenotypic differences, and thus this may be a general mechanism for mediating extensive regulatory (e.g., expression and binding QTLs) and phenotypic variation in all eukaryotes. "
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    ABSTRACT: Genetic basis of phenotypic differences in individuals is an important area in biology and personalized medicine. Analysis of divergent Saccharomyces cerevisiae strains grown under different conditions revealed extensive variation in response to both drugs (e.g., 4-nitroquinoline 1-oxide [4NQO]) and different carbon sources. Differences in 4NQO resistance were due to amino acid variation in the transcription factor Yrr1. Yrr1(YJM789) conferred 4NQO resistance but caused slower growth on glycerol, and vice versa with Yrr1(S96), indicating that alleles of Yrr1 confer distinct phenotypes. The binding targets of Yrr1 alleles from diverse yeast strains varied considerably among different strains grown under the same conditions as well as for the same strain under different conditions, indicating that distinct molecular programs are conferred by the different Yrr1 alleles. Our results demonstrate that genetic variations in one important control gene (YRR1), lead to distinct regulatory programs and phenotypes in individuals. We term these polymorphic control genes "master variators."
    Genes & development 02/2014; 28(4):409-21. DOI:10.1101/gad.228940.113 · 10.80 Impact Factor
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    • "These strains are often difficult or impossible to sporulate, which suggests that the ability to undergo sexual cycle degenerates in human-made environments (Johnston 1994). An example of a likely joint action of these factors—smaller population size, benign and specific environment, possible adaptation, and asexual reproduction—has been provided by a study in which a laboratory strain of confirmed history of “domestication” was found to undergo an accelerated rate of molecular evolution, demonstrating considerable relaxation of the purifying selection (Gu et al. 2005). "
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    ABSTRACT: Crosses between inbred but unrelated individuals often result in an increased fitness of the progeny. This phenomenon is known as heterosis and was reported both for wild and domesticated populations of plants and animals. Analysis of heterosis is often hindered by the fact that the genetic relatedness between analyzed organisms is known only approximately. We studied a collection of Saccharomyces cerevisiae isolates from wild and human-created habitats whose genomes were sequenced and thus their relatedness is fully known. We reasoned that if these strains accumulated different deleterious mutations at a roughly constant rate, then heterosis should be most visible in F1 heterozygotes from the least related parents. We found that heterosis was substantial and positively correlated with sequence divergence, but only in domesticated strains. More than eighty percent of the heterozygous hybrids were more fit than expected from the mean of their homozygous parents, and about three quarters of those exceeded even the fittest parent. Our results support the notion that domestication brings about relaxation of selection and accumulation of deleterious mutations. However, other factors may have contributed as well. In particular, the observed buildup of genetic load might be facilitated by a decrease and not increase in the rate of inbreeding.
    G3-Genes Genomes Genetics 12/2013; 4(2). DOI:10.1534/g3.113.009381 · 3.20 Impact Factor
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