| 1. |
- Ablikim, M., et al.
(author)
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Measurement of branching fractions for psi(3686) -> gamma eta ', gamma eta, and gamma pi(0)
- 2017
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In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 96:5
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Journal article (peer-reviewed)abstract
- Using a data sample of 448 x 10(6) psi(3686) events collected with the BESIII detector operating at the BEPCII storage ring, the decays psi(3686) -> gamma eta and psi(3686) -> gamma pi(0) are observed with a statistical significance of 7.3 sigma and 6.7 sigma, respectively. The branching fractions are measured to be B(psi(3686) -> gamma eta) = (0.85 +/- 0.18 +/- 0.05) x 10(-6) and B(psi(3686) ->gamma pi(0)) = (0.95 +/- 0.16 +/- 0.05) x 10(-6). In addition, we measure the branching fraction of psi(3686) -> gamma eta' to be B(psi(3686) -> gamma eta') = (125.1 +/- 2.2 +/- 6.2)x10(-6), which represents an improvement of precision over previous results.
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| 2. |
- Yue, J. X., et al.
(author)
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Contrasting evolutionary genome dynamics between domesticated and wild yeasts
- 2017
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:6
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Journal article (peer-reviewed)abstract
- 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 yeast Saccharomyces cerevisiae and its wild relative Saccharomyces 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. paradoxus shows faster accumulation of balanced rearrangements (inversions, reciprocal translocations and transpositions), whereas S. cerevisiae accumulates unbalanced rearrangements (novel insertions, deletions and duplications) more rapidly. In subtelomeres, both species show extensive interchromosomal reshuffling, with a higher tempo in S. cerevisiae. Such striking contrasts between wild and domesticated yeasts are likely to reflect the influence of human activities on structural genome evolution.
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| 3. |
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| 4. |
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| 5. |
- D'Angiolo, M., et al.
(author)
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A yeast living ancestor reveals the origin of genomic introgressions
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587, s. 420-425
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Journal article (peer-reviewed)abstract
- A yeast clonal descendant of an ancient hybridization event is identified and sheds light on the early evolution of the Saccharomyces cerevisiae Alpechin lineage and its abundant Saccharomyces paradoxus introgressions. Genome introgressions drive evolution across the animal(1), plant(2) and fungal(3) kingdoms. Introgressions initiate from archaic admixtures followed by repeated backcrossing to one parental species. However, how introgressions arise in reproductively isolated species, such as yeast(4), has remained unclear. Here we identify a clonal descendant of the ancestral yeast hybrid that founded the extant Saccharomyces cerevisiae Alpechin lineage(5), which carries abundant Saccharomyces paradoxus introgressions. We show that this clonal descendant, hereafter defined as a 'living ancestor', retained the ancestral genome structure of the first-generation hybrid with contiguous S. cerevisiae and S. paradoxus subgenomes. The ancestral first-generation hybrid underwent catastrophic genomic instability through more than a hundred mitotic recombination events, mainly manifesting as homozygous genome blocks generated by loss of heterozygosity. These homozygous sequence blocks rescue hybrid fertility by restoring meiotic recombination and are the direct origins of the introgressions present in the Alpechin lineage. We suggest a plausible route for introgression evolution through the reconstruction of extinct stages and propose that genome instability allows hybrids to overcome reproductive isolation and enables introgressions to emerge.
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| 6. |
- Hallin, J., et al.
(author)
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Powerful decomposition of complex traits in a diploid model
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Explaining trait differences between individuals is a core and challenging aim of life sciences. Here, we introduce a powerful framework for complete decomposition of trait variation into its underlying genetic causes in diploid model organisms. We sequence and systematically pair the recombinant gametes of two intercrossed natural genomes into an array of diploid hybrids with fully assembled and phased genomes, termed Phased Outbred Lines (POLs). We demonstrate the capacity of this approach by partitioning fitness traits of 6,642 Saccharomyces cerevisiae POLs across many environments, achieving near complete trait heritability and precisely estimating additive (73%), dominance (10%), second (7%) and third (1.7%) order epistasis components. We map quantitative trait loci (QTLs) and find nonadditive QTLs to outnumber (3:1) additive loci, dominant contributions to heterosis to outnumber overdominant, and extensive pleiotropy. The POL framework offers the most complete decomposition of diploid traits to date and can be adapted to most model organisms.
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| 7. |
- Li, J., et al.
(author)
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Genome instability footprint under rapamycin and hydroxyurea treatments
- 2023
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In: PLoS Genetics. - 1553-7404. ; 19:11
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Journal article (peer-reviewed)abstract
- The mutational processes dictating the accumulation of mutations in genomes are shaped by genetic background, environment and their interactions. Accurate quantification of mutation rates and spectra under drugs has important implications in disease treatment. Here, we used whole-genome sequencing and time-resolved growth phenotyping of yeast mutation accumulation lines to give a detailed view of the mutagenic effects of rapamycin and hydroxyurea on the genome and cell growth. Mutation rates depended on the genetic backgrounds but were only marginally affected by rapamycin. As a remarkable exception, rapamycin treatment was associated with frequent chromosome XII amplifications, which compensated for rapamycin induced rDNA repeat contraction on this chromosome and served to maintain rDNA content homeostasis and fitness. In hydroxyurea, a wide range of mutation rates were elevated regardless of the genetic backgrounds, with a particularly high occurrence of aneuploidy that associated with dramatic fitness loss. Hydroxyurea also induced a high T-to-G and low C-to-A transversion rate that reversed the common G/C-to-A/T bias in yeast and gave rise to a broad range of structural variants, including mtDNA deletions. The hydroxyurea mutation footprint was consistent with the activation of error-prone DNA polymerase activities and non-homologues end joining repair pathways. Taken together, our study provides an in-depth view of mutation rates and signatures in rapamycin and hydroxyurea and their impact on cell fitness, which brings insights for assessing their chronic effects on genome integrity. As the ultimate source of genetic variation, mutation plays critical roles in evolution. An accurate depiction of its intrinsic rate and signature can help us understand the genetic basis of biodiversity and diseases. However, the ubiquitous existence of natural selection often leads to bias for the observable mutations in natural populations. To minimize such confounding effect introduced by selection, we applied evolution experiment by random single-cell bottlenecks, which allows almost all kinds of mutations to accumulate in an unbiased way. With this setup, we examined the mutation rates and signatures of yeast cells in two commonly used chemotherapy drugs that impairs essential cellular functions such as DNA and protein synthesis. We found elevated mutation rates for a wide range of genetic variants, accompanied by dramatic fitness loss in hydroxyurea. The mutational signatures suggest the involvement of low fidelity DNA replication and repair processes. The mutagenic effects of rapamycin are marginal but with frequent chromosome XII amplifications that compensate for rapamycin-induced rDNA contraction on this chromosome. Our findings provide an example of how such experiments on model organisms can help us better understand the chronic mutagenic effects of drugs and their underlying biological mechanisms.
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| 8. |
- Liti, G, et al.
(author)
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Budding Yeast Strainsand Genotype-Phenotype mapping
- 2015
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In: CSHLprotocol series “Budding Yeast: ALaboratory Manual”. - : Cold Spring Harbor Laboratory.
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Book chapter (peer-reviewed)abstract
- A small number of well-studied laboratory strains of Saccharomyces cerevisiae, mostly derived from S288C, are used in yeast research. Although powerful, studies for understanding S288C do not always capture the phenotypic essence or the genetic complexity of S. cerevisiae biology. This is particularly problematic for multilocus phenotypes identified in laboratory strains because these loci have never been jointly exposed to natural selection and the corresponding phenotypes do not represent optimization for any particular purpose or environment. Isolation and sequencing of new natural yeast strains also reveal that the total sequence diversity of the S. cerevisiae global population is poorly sampled in common laboratory strains. Here we discuss methodologies required for using the natural genetic variation in yeast to complete a genotype–phenotype map.
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| 9. |
- Liti, G., et al.
(author)
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Isolation and laboratory domestication of natural yeast strain
- 2017
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In: Cold Spring Harbor Protocols. - : Cold Spring Harbor Laboratory. - 1940-3402 .- 1559-6095. ; :8, s. 626-630
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Journal article (peer-reviewed)abstract
- The process from yeast isolation to their use in laboratory experiments is lengthy. Historically, Saccharomyces strains were easily obtained by sampling alcoholic fermentation processes or other substrates associated with human activity in which Saccharomyces was heavily enriched. In contrast, wild Saccharomyces yeasts are found in complex microbial communities and small population sizes, making isolation challenging. We have overcome this problem by enriching yeast on media favoring the growth of Saccharomyces over other microorganisms. The isolation process is usually followed by molecular characterization that allows the strain identification. Finally, yeast isolated from domestic or wild environments need to be genetically manipulated before they can be used in laboratory experiments. © 2017 Cold Spring Harbor Laboratory Press.
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| 10. |
- Liti, G., et al.
(author)
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Mapping quantitative trait loci in yeast
- 2017
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In: Cold Spring Harbor Protocols. - : Cold Spring Harbor Laboratory. - 1940-3402 .- 1559-6095. ; 2017:8, s. 631-635
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Journal article (peer-reviewed)abstract
- Natural Saccharomyces strains isolated from the wild differ quantitatively in molecular and organismal phenotypes. Quantitative trait loci (QTL) mapping is a powerful approach for identifying sequence variants that alter gene function. In yeast, QTL mapping has been used in designed crosses to map functional polymorphisms. This approach, outlined here, is often the first step in understanding the molecular basis of quantitative traits. New large-scale sequencing surveys have the potential to directly associate genotypes with organismal phenotypes, providing a broader catalog of causative genetic variants. Additional analysis of intermediate phenotypes (e.g., RNA, protein, or metabolite levels) can produce a multilayered and integrated view of individual variation, producing a high-resolution view of the genotype–phenotype map. © 2017 Cold Spring Harbor Laboratory Press.
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| 11. |
- Mozzachiodi, S., et al.
(author)
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Aborting meiosis allows recombination in sterile diploid yeast hybrids
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Hybrids are often considered evolutionary dead ends because they do not generate viable offspring. Here, the authors show that sterile yeast hybrids generate genetic diversity through meiotic-like recombination by aborting meiosis and return to asexual growth. Hybrids between diverged lineages contain novel genetic combinations but an impaired meiosis often makes them evolutionary dead ends. Here, we explore to what extent an aborted meiosis followed by a return-to-growth (RTG) promotes recombination across a panel of 20 Saccharomyces cerevisiae and S. paradoxus diploid hybrids with different genomic structures and levels of sterility. Genome analyses of 275 clones reveal that RTG promotes recombination and generates extensive regions of loss-of-heterozygosity in sterile hybrids with either a defective meiosis or a heavily rearranged karyotype, whereas RTG recombination is reduced by high sequence divergence between parental subgenomes. The RTG recombination preferentially arises in regions with low local heterozygosity and near meiotic recombination hotspots. The loss-of-heterozygosity has a profound impact on sexual and asexual fitness, and enables genetic mapping of phenotypic differences in sterile lineages where linkage analysis would fail. We propose that RTG gives sterile yeast hybrids access to a natural route for genome recombination and adaptation.
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| 12. |
- Van Wonterghem, L., et al.
(author)
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Genome-Wide Association Study Reveals Host Factors Affecting Conjugation in Escherichia coli
- 2022
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In: Microorganisms. - : MDPI AG. - 2076-2607. ; 10:3
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Journal article (peer-reviewed)abstract
- The emergence and dissemination of antibiotic resistance threaten the treatment of common bacterial infections. Resistance genes are often encoded on conjugative elements, which can be horizontally transferred to diverse bacteria. In order to delay conjugative transfer of resistance genes, more information is needed on the genetic determinants promoting conjugation. Here, we focus on which bacterial host factors in the donor assist transfer of conjugative plasmids. We introduced the broad-host-range plasmid pKJK10 into a diverse collection of 113 Escherichia coli strains and measured by flow cytometry how effectively each strain transfers its plasmid to a fixed E. coli recipient. Differences in conjugation efficiency of up to 2.7 and 3.8 orders of magnitude were observed after mating for 24 h and 48 h, respectively. These differences were linked to the underlying donor strain genetic variants in genome-wide association studies, thereby identifying candidate genes involved in conjugation. We confirmed the role of fliF, fliK, kefB and ucpA in the donor ability of conjugative elements by validating defects in the conjugation efficiency of the corresponding lab strain single-gene deletion mutants. Based on the known cellular functions of these genes, we suggest that the motility and the energy supply, the intracellular pH or salinity of the donor affect the efficiency of plasmid transfer. Overall, this work advances the search for targets for the development of conjugation inhibitors, which can be administered alongside antibiotics to more effectively treat bacterial infections.
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| 13. |
- Vazquez-Garcia, I., et al.
(author)
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Clonal Heterogeneity Influences the Fate of New Adaptive Mutations
- 2017
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 21:3, s. 732-744
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Journal article (peer-reviewed)abstract
- The joint contribution of pre-existing and de novo genetic variation to clonal adaptation is poorly understood but essential to designing successful antimicrobial or cancer therapies. To address this, we evolve genetically diverse populations of budding yeast, S. cerevisiae, consisting of diploid cells with unique haplotype combinations. We study the asexual evolution of these populations under selective inhibition with chemotherapeutic drugs by time-resolved whole-genome sequencing and phenotyping. All populations undergo clonal expansions driven by de novo mutations but remain genetically and phenotypically diverse. The clones exhibit widespread genomic instability, rendering recessive de novo mutations homozygous and refining pre-existing variation. Finally, we decompose the fitness contributions of pre-existing and de novo mutations by creating a large recombinant library of adaptive mutations in an ensemble of genetic backgrounds. Both pre-existing and de novo mutations substantially contribute to fitness, and the relative fitness of preexisting variants sets a selective threshold for new adaptive mutations.
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| 14. |
- Warringer, Jonas, 1973, et al.
(author)
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Yeast reciprocal hemizygosity to confirm the causality of a quantitative trait loci-associated gene
- 2017
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In: Cold Spring Harbor Protocols. - : Cold Spring Harbor Laboratory. - 1940-3402 .- 1559-6095. ; :8, s. 636-640
-
Journal article (peer-reviewed)abstract
- Pinpointing causal alleles within a quantitative trait loci region is a key challenge when dissecting the genetic basis of natural variation. In yeast, homing in on culprit genes is often achieved using engineered reciprocal hemizygotes as outlined here. Based on prior information on gene–trait associations, candidate genes are identified. In haploid versions of both founder strains, a candidate gene is then deleted. Gene knockouts are independently mated to a wild-type version of the other strain, such that two diploid hybrid strains are obtained. These strains are identical with regard to the nuclear genome, except for that they are hemizygotic at the locus of interest and contain different alleles of the candidate gene. If correctly measured, a trait difference between these reciprocal hemizygotes can confidently be ascribed to allelic variation at the target locus. © 2017 Cold Spring Harbor Laboratory Press.
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| 15. |
- Zörgö, Enikö, 1968, et al.
(author)
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Ancient Evolutionary Trade-Offs between Yeast Ploidy States
- 2013
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In: Plos Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 9:3
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Journal article (peer-reviewed)abstract
- The number of chromosome sets contained within the nucleus of eukaryotic organisms is a fundamental yet evolutionarily poorly characterized genetic variable of life. Here, we mapped the impact of ploidy on the mitotic fitness of baker's yeast and its never domesticated relative Saccharomyces paradoxus across wide swaths of their natural genotypic and phenotypic space. Surprisingly, environment-specific influences of ploidy on reproduction were found to be the rule rather than the exception. These ploidy–environment interactions were well conserved across the 2 billion generations separating the two species, suggesting that they are the products of strong selection. Previous hypotheses of generalizable advantages of haploidy or diploidy in ecological contexts imposing nutrient restriction, toxin exposure, and elevated mutational loads were rejected in favor of more fine-grained models of the interplay between ecology and ploidy. On a molecular level, cell size and mating type locus composition had equal, but limited, explanatory power, each explaining 12.5%–17% of ploidy–environment interactions. The mechanism of the cell size–based superior reproductive efficiency of haploids during Li+ exposure was traced to the Li+ exporter ENA. Removal of the Ena transporters, forcing dependence on the Nha1 extrusion system, completely altered the effects of ploidy on Li+ tolerance and evoked a strong diploid superiority, demonstrating how genetic variation at a single locus can completely reverse the relative merits of haploidy and diploidy. Taken together, our findings unmasked a dynamic interplay between ploidy and ecology that was of unpredicted evolutionary importance and had multiple molecular roots.
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