Current lab members:

• Gianni LITI, Research Director, DR1 CNRS
• Agnes Llored (Lab Manager)
• Federica Carlea (PhD student)
• Sakshi Khaiwal (PhD student)
• Simon Laugier (PhD student)
• Danielle Adekunle (Post-doc)
• Matteo De Chiara (Post-doc)
• Benjamin Barré (Post-doc)
• Xanita Saayman (Post-doc)
• Lorenzo Tattini (Post-doc)
• Nicolo Tellini (Post-doc)
• Chiara Vischioni (Post-doc)

Lab Alumni:

Most human traits, including cancer susceptibility and ageing, are regulated by multiple interacting quantitative trait loci (QTLs). Dissecting the genetic mechanisms underlying this phenotypic variation is a major challenge. In order to advance our understanding of complex traits there is a need for a suitable genetic system that can be used in high-throughput studies. In our lab, we use the budding yeast, S. cerevisiae, to dissect the genetic architecture of multiple traits. The objectives are relevant for human health in two ways: the first consists of modelling complex traits in a simple genetic system; the second aims to dissect traits directly relevant to the complex biology of cancer and ageing. In all aspects of our research, we exploit natural variation in the budding yeast as a tool for understanding how a phenotype is genetically regulated. Given that many pathways (e.g. longevity) are conserved from yeast to humans, there is an opportunity to test previously uncharacterised genes in other model systems. Once the architecture of complex traits is fully dissected, the next step is to extrapolate this knowledge to make predictions (based on population genomics data) of the standing variation in natural populations. Finally, the long-term challenge is to understand what evolutionary forces maintain the variability in natural populations.

Current Projects

Top Publications

• Ancient and recent origins of shared polymorphisms in yeast
  13 mars 2024 par Nicolò Tellini
  Shared genetic polymorphisms between populations and species can be ascribed to ancestral variation or to more recent gene flow. Here, we mapped shared polymorphisms in Saccharomyces cerevisiae and its sister species Saccharomyces paradoxus, which diverged 4-6 million years ago. We used a dense map of single-nucleotide diagnostic markers (mean distance 15.6 base pairs) in 1,673 sequenced S. cerevisiae isolates to catalogue 3,852 sequence blocks (≥5 consecutive markers) introgressed from S….
• Genome instability footprint under rapamycin and hydroxyurea treatments
  6 novembre 2023 par Jing Li
  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…
• Telomeres are shorter in wild Saccharomyces cerevisiae isolates than in domesticated ones
  23 décembre 2022 par Melania D'Angiolo
  Telomeres are ribonucleoproteins that cap chromosome-ends and their DNA length is controlled by counteracting elongation and shortening processes. The budding yeast Saccharomyces cerevisiae has been a leading model to study telomere DNA length control and dynamics. Its telomeric DNA is maintained at a length that slightly varies between laboratory strains, but little is known about its variation at the species level. The recent publication of the genomes of over 1,000 S. cerevisiae strains…
• Editorial overview: evolutionary genetics: how a tiny model system enables big discoveries
  21 octobre 2022 par Christian R Landry
  No abstract
• Evolution of yeast hybrids by aborted meiosis
  9 septembre 2022 par Simone Mozzachiodi
  Sterile hybrids are broadly considered evolutionary dead-ends because of their faulty sexual reproduction. While sterility in obligate sexual organisms is a clear constraint in perpetuating the species, some facultative sexual microbes such as yeasts can propagate asexually and maintain genome plasticity. Moreover, incomplete meiotic pathways in yeasts represent alternative routes to the standard meiosis that generates genetic combinations in the population and fuel adaptation. Here, we review…
• Unlocking the functional potential of polyploid yeasts
  11 mai 2022 par Simone Mozzachiodi
  Breeding and domestication have generated widely exploited crops, animals and microbes. However, many Saccharomyces cerevisiae industrial strains have complex polyploid genomes and are sterile, preventing genetic improvement strategies based on breeding. Here, we present a strain improvement approach based on the budding yeasts' property to promote genetic recombination when meiosis is interrupted and cells return-to-mitotic-growth (RTG). We demonstrate that two unrelated sterile industrial…
• Domestication reprogrammed the budding yeast life cycle
  25 février 2022 par Matteo De Chiara
  Domestication of plants and animals is the foundation for feeding the world human population but can profoundly alter the biology of the domesticated species. Here we investigated the effect of domestication on one of our prime model organisms, the yeast Saccharomyces cerevisiae, at a species-wide level. We tracked the capacity for sexual and asexual reproduction and the chronological life span across a global collection of 1,011 genome-sequenced yeast isolates and found a remarkable dichotomy…
• Aborting meiosis allows recombination in sterile diploid yeast hybrids
  13 novembre 2021 par Simone Mozzachiodi
  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…
• A yeast living ancestor reveals the origin of genomic introgressions
  12 novembre 2020 par Melania D'Angiolo
  Genome introgressions drive evolution across the animal¹, plant² and fungal³ kingdoms. Introgressions initiate from archaic admixtures followed by repeated backcrossing to one parental species. However, how introgressions arise in reproductively isolated species, such as yeast⁴, has remained unclear. Here we identify a clonal descendant of the ancestral yeast hybrid that founded the extant Saccharomyces cerevisiae Alpechin lineage⁵, which carries abundant Saccharomyces paradoxus introgressions….
• Discordant evolution of mitochondrial and nuclear yeast genomes at population level
  13 mai 2020 par Matteo De Chiara
  CONCLUSIONS: Overall, our results illustrate how differences in the biology of two genomes coexisting in the same cells can lead to discordant evolutionary histories.
• Intragenic repeat expansion in the cell wall protein gene <em>HPF1</em> controls yeast chronological aging
  12 avril 2020 par Benjamin P Barré
  Aging varies among individuals due to both genetics and environment, but the underlying molecular mechanisms remain largely unknown. Using a highly recombined Saccharomyces cerevisiae population, we found 30 distinct quantitative trait loci (QTLs) that control chronological life span (CLS) in calorie-rich and calorie-restricted environments and under rapamycin exposure. Calorie restriction and rapamycin extended life span in virtually all genotypes but through different genetic variants. We…
• Accurate Tracking of the Mutational Landscape of Diploid Hybrid Genomes
  10 août 2019 par Lorenzo Tattini
  Mutations, recombinations, and genome duplications may promote genetic diversity and trigger evolutionary processes. However, quantifying these events in diploid hybrid genomes is challenging. Here, we present an integrated experimental and computational workflow to accurately track the mutational landscape of yeast diploid hybrids (MuLoYDH) in terms of single-nucleotide variants, small insertions/deletions, copy-number variants, aneuploidies, and loss-of-heterozygosity. Pairs of haploid…
• simuG: a general-purpose genome simulator
  23 mai 2019 par Jia-Xing Yue
  SUMMARY: Simulated genomes with pre-defined and random genomic variants can be very useful for benchmarking genomic and bioinformatics analyses. Here we introduce simuG, a lightweight tool for simulating the full-spectrum of genomic variants (single nucleotide polymorphisms, Insertions/Deletions, copy number variants, inversions and translocations) for any organisms (including human). The simplicity and versatility of simuG make it a unique general-purpose genome simulator for a wide-range of…
• Shared Molecular Targets Confer Resistance over Short and Long Evolutionary Timescales
  19 janvier 2019 par Jing Li
  Pre-existing and de novo genetic variants can both drive adaptation to environmental changes, but their relative contributions and interplay remain poorly understood. Here we investigated the evolutionary dynamics in drug-treated yeast populations with different levels of pre-existing variation by experimental evolution coupled with time-resolved sequencing and phenotyping. We found a doubling of pre-existing variation alone boosts the adaptation by 64.1% and 51.5% in hydroxyurea and rapamycin,…
• Long-read sequencing data analysis for yeasts
  5 mai 2018 par Jia-Xing Yue
  Long-read sequencing technologies have become increasingly popular due to their strengths in resolving complex genomic regions. As a leading model organism with small genome size and great biotechnological importance, the budding yeast Saccharomyces cerevisiae has many isolates currently being sequenced with long reads. However, analyzing long-read sequencing data to produce high-quality genome assembly and annotation remains challenging. Here, we present a modular computational framework named…
• Clonal Heterogeneity Influences the Fate of New Adaptive Mutations
  19 octobre 2017 par Ignacio Vázquez-García
  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…
• Isolation and Laboratory Domestication of Natural Yeast Strains
  3 août 2017 par Gianni Liti
  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…
• Mapping Quantitative Trait Loci in Yeast
  3 août 2017 par Gianni Liti
  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…
• Budding Yeast Strains and Genotype-Phenotype Mapping
  3 août 2017 par Gianni Liti
  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…
• Contrasting evolutionary genome dynamics between domesticated and wild yeasts
  19 avril 2017 par Jia-Xing Yue
  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…

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