GMGM - Génétique moléculaire, génomique, microbiologie - Université de Strasbourg https://gmgm.unistra.fr fr GMGM - Génétique moléculaire, génomique, microbiologie - Université de Strasbourg Tue, 27 Feb 2024 08:54:50 +0100 Tue, 27 Feb 2024 08:54:50 +0100 TYPO3 EXT:news news-16045 Fri, 23 Feb 2024 11:00:00 +0100 Invited GMGM seminar: Tobias BOLLENBACH (University of Cologne, Institute for Biological Physics) /en/news/piece-of-news/invited-gmgm-seminar-tobias-bollenbach-university-of-cologne-institute-for-biological-physics Systematic disruption of antibiotic resistance evolution Agenda du GMGM news-16111 Fri, 16 Feb 2024 12:06:18 +0100 New publication of the team /en/news/piece-of-news/nouvelle-publication-de-lequipe Diallel panel reveals a significant impact of low-frequency genetic variants on gene expression variation in yeast.
Andreas Tsouris, Gauthier Brach, Anne Friedrich, Jing Hou, Joseph Schacherer.
Mol Syst Biol. 2024. doi:10.1038/s44320-024-00021-0

Unraveling the genetic sources of gene expression variation is essential to better understand the origins of phenotypic diversity in natural populations. Genome-wide association studies identified thousands of variants involved in gene expression variation, however, variants detected only explain part of the heritability. In fact, variants such as low-frequency and structural variants (SVs) are poorly captured in association studies. To assess the impact of these variants on gene expression variation, we explored a half-diallel panel composed of 323 hybrids originated from pairwise crosses of 26 natural Saccharomyces cerevisiae isolates. Using short- and long-read sequencing strategies, we established an exhaustive catalog of single nucleotide polymorphisms (SNPs) and SVs for this panel. Combining this dataset with the transcriptomes of all hybrids, we comprehensively mapped SNPs and SVs associated with gene expression variation. While SVs impact gene expression variation, SNPs exhibit a higher effect size with an overrepresentation of low-frequency variants compared to common ones. These results reinforce the importance of dissecting the heritability of complex traits with a comprehensive catalog of genetic variants at the population level.

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Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-15600 Thu, 01 Feb 2024 11:00:00 +0100 Invited GMGM seminar: Ilana KOLODKIN-GAL (Reichman University, Ben-Gurion University) /en/news/piece-of-news/invited-gmgm-seminar-ilana-kolodkin-gal-reichman-university-ben-gurion-university Communal behaviors of microbial communities: from antibiotic production to carbon dioxide sequestration Agenda du GMGM news-16032 Tue, 30 Jan 2024 20:46:48 +0100 New publication in NAR /en/news/piece-of-news/nouvelle-publcation-dans-nar Translation variation across genetic backgrounds reveals a post-transcriptional buffering signature in yeast.
Elie M Teyssonniere, Yuichi Shichino, Mari Mito, Anne Friedrich, Shintaro Iwasaki, Joseph Schacherer.
Nucleic Acids Research. 2024. doi:10.1093/nar/gkae030
 

Gene expression is known to vary among individuals, and this variability can impact the phenotypic diversity observed in natural populations. While the transcriptome and proteome have been extensively studied, little is known about the translation process itself. Here, we therefore performed ribosome and transcriptomic profiling on a genetically and ecologically diverse set of natural isolates of the Saccharomyces cerevisiae yeast. Interestingly, we found that the Euclidean distances between each profile and the expression fold changes in each pairwise isolate comparison were higher at the transcriptomic level. This observation clearly indicates that the transcriptional variation observed in the different isolates is buffered through a phenomenon known as post-transcriptional buffering at the translation level. Furthermore, this phenomenon seemed to have a specific signature by preferentially affecting essential genes as well as genes involved in complex-forming proteins, and low transcribed genes. We also explored the translation of the S. cerevisiae pangenome and found that the accessory genes related to introgression events displayed similar transcription and translation levels as the core genome. By contrast, genes acquired through horizontal gene transfer events tended to be less efficiently translated. Together, our results highlight both the extent and signature of the post-transcriptional buffering.

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Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-15835 Fri, 19 Jan 2024 15:55:17 +0100 New publication in PLos Genetics /en/news/piece-of-news/nouvelle-publication-dans-plos-genetics-1 Species-wide survey of the expressivity and complexity spectrum of traits in yeast.
Andreas Tsouris, Téo Fournier, Anne Friedrich, Jing Hou, Maitreya J. Dunham, Joseph Schacherer.

Assessing the complexity and expressivity of traits at the species level is an essential first step to better dissect the genotype-phenotype relationship. As trait complexity behaves dynamically, the classic dichotomy between monogenic and complex traits is too simplistic. However, no systematic assessment of this complexity spectrum has been carried out on a population scale to date. In this context, we generated a large diallel hybrid panel composed of 190 unique hybrids coming from 20 natural isolates representative of the S. cerevisiae genetic diversity. For each of these hybrids, a large progeny of 160 individuals was obtained, leading to a total of 30,400 offspring individuals. Their mitotic growth was evaluated on 38 conditions inducing various cellular stresses. We developed a classification algorithm to analyze the phenotypic distributions of offspring and assess the trait complexity. We clearly found that traits are mainly complex at the population level. On average, we found that 91.2% of cross/trait combinations exhibit high complexity, while monogenic and oligogenic cases accounted for only 4.1% and 4.7%, respectively. However, the complexity spectrum is very dynamic, trait specific and tightly related to genetic backgrounds. Overall, our study provided greater insight into trait complexity as well as the underlying genetic basis of its spectrum in a natural population.

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Actualités du GMGM Actualités de l'Équipe Schacherer
news-15743 Thu, 18 Jan 2024 10:14:38 +0100 Strasbourg : à la recherche de la « super-bactérie » (DNA ; 17/01/24) /en/news/piece-of-news/lequipe-aime-dans-les-dna-17-01-24 À l’université de Strasbourg, des chercheurs traquent les micro-organismes qui pourraient un jour gommer certains des micropolluants qui s’accumulent dans notre environnement. Ils ont déjà réussi à isoler une bactérie capable de digérer la molécule d’un médicament très utilisé. Actualités du GMGM Actualités de l'Équipe Vuilleumier news-15617 Mon, 15 Jan 2024 10:14:40 +0100 New publication in Cell Genomics /en/news/piece-of-news/nouvelle-publication-dans-cell-genomics Non-additive genetic components contribute significantly to population-wide gene expression variation.
Andreas Tsouris, Gauthier Brach, Joseph Schacherer, Jing Hou.

Gene expression variation, an essential step between genotype and phenotype, is collectively controlled by local (cis) and distant (trans) regulatory changes. Nevertheless, how these regulatory elements differentially influence gene expression variation remains unclear. Here, we bridge this gap by analyzing the transcriptomes of a large diallel panel consisting of 323 unique hybrids originating from genetically divergent Saccharomyces cerevisiae isolates. Our analysis across 5,087 transcript abundance traits showed that non-additive components account for 36% of the gene expression variance on average. By comparing allele-specific read counts in parent-hybrid trios, we found that trans-regulatory changes underlie the majority of gene expression variation in the population. Remarkably, most cis-regulatory variations are also exaggerated or attenuated by additional trans effects. Overall, we showed that the transcriptome is globally buffered at the genetic level mainly due to trans-regulatory variation in the population.

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Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-15575 Fri, 22 Dec 2023 11:24:15 +0100 Polluants éternels: en quête d'une bactérie mangeuse de PFAs (ARTE Info, 16 Décembre 2023) /en/news/piece-of-news/polluants-eternels-en-quete-dune-bacterie-mangeuse-de-pfas-arte-16-decembre-2023 Actualités du GMGM Actualités de l'Équipe Vuilleumier news-15411 Wed, 22 Nov 2023 08:36:22 +0100 Montrer les invisibles du sol : dialogue entre étudiants en design et microbiologistes de l’équipe AIME du GMGM /en/news/piece-of-news/montrer-les-invisibles-du-sol-dialogue-entre-etudiants-en-design-et-microbiologistes-de-lequipe-aime-du-gmgm Montrer les invisibles du sol :
dialogue entre étudiants en design et microbiologistes de l’équipe AIME du GMGM

14 octobre 2023 : ‘École Vivrière’ au CSC de la Roberstau à Strasbourg (https://www.lyceelecorbusier.eu/dsaa/?p=3730)

 

 

Les étudiant.e.s d’arts appliqués du Lycée le Corbusier à Illkirch ont eu l’occasion, dans le cadre de leur résidence de design, de dialoguer avec Dr. Emilie Muller et Dr. Françoise Bringel sur les invisibles du sol. Ces microorganismes ont fasciné par leur rôle dans l’environnement mais aussi par leur diversité de formes, de textures et de couleurs quand ils sont rendus visibles après culture (15 jours à 17°C) sur boite de Pétri, à partir d’empreintes de feuilles, ou d’étalement d’eaux de pluie, de rivière ou de mare, ou encore de suspension de sols et de compost (voir photos ci-contre). Le tout prélevé sur le site ou directement aux alentours, rendant tangibles les microbiomes du quotidien, d’ordinaire imperceptibles.

 

 

 

 

Afin de continuer à croiser les regards sur ce qu’est un sol, la soirée a été consacrée à un dialogue entre des professionnels et des curieux du sol : designers, artistes, botanistes, géologues, agents des espaces verts, maraîchers, microbiologistes, sociologues, notaires, enseignants et habitants. Dans une ambiance joueuse autant que sérieuse, le maître de cérémonie de ce premier conseil des sols a fait en sorte de nouer un dialogue sur cet objet dont la définition même est dépendante de l’interlocuteur !

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Actualités du GMGM Actualités de l'Équipe Vuilleumier
news-15356 Tue, 14 Nov 2023 13:09:10 +0100 New publication of Emilie MULLER (team AIME) in Nature Ecology & Evolution /en/news/piece-of-news/new-publication-of-emilie-muller-in-nature-ecology-evolution Microbiomes are essential for safeguarding health in humans and the environment, and are central to sustainability. A key microbiome-based technology is biological wastewater treatment, the most widely used biotechnological process on Earth. The process itself is subject to constant changes and does not fulfill the premise of sustainability. There is therefore an urgent need to predict the behaviour of its complex microbiomes to better control the process and to improve on its engineering. The Luxembourg Centre for Systems Biomedicine & the Department of Life Sciences and Medicine at the University of Luxembourg alongside with international collaborators has now developed a unique and novel modelling approach that can predict the dynamics and functions of such microbiomes several years into the future. This framework can also be applied to other key ecosystems, be it the human gut microbiome or pristine environments facing disturbance.


Research at University of Luxembourg, Norwegian University of Life Sciences, Medical University of Vienna, Centre National de La Recherche Scientifique (CNRS) & University of Strasbourg.
Funding by Luxembourg National Research Fund - FNR, European Research Council, European Commission, Austrian Science Fund FWF, Novo Nordisk Foundation & IBBL at  Luxembourg Institute of Health.

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Actualités du GMGM Actualités de l'Équipe Vuilleumier
news-14802 Fri, 27 Oct 2023 11:00:00 +0200 Invited GMGM seminar: Wolfram S. KUNZ (University Bonn) /en/news/piece-of-news/invited-gmgm-seminar-wolfram-s-kunz-university-bonn Removal of oxidative lesions in mtDNA Agenda du GMGM news-14855 Mon, 23 Oct 2023 16:14:07 +0200 Fête de la Science Lingolsheim 6 au 8 octobre 2023 /en/news/piece-of-news/fete-de-la-science-lingolsheim-6-au-8-octobre-2023 GMGM a organisé et présenté la fête de la Science à Lingolsheim du 6 au 8 octobre 2023. Les membres de l'équipe Friant et Becker ont été impliqués dans divers ateliers :
- environnement: le monde des abeilles et de l'apithérapie
- écologie: la levure pour visualiser l'effet de cocktails de pesticides
- biodiversité: les champignons filamenteux, les observer et les comprendre
- Sciences participatives: Avec le jeu Mendeleieva, découvrez les éléments chimiques de votre vie de tous les jours et des femmes scientifiques étudiant ces éléments.

D'autres ateliers étaient proposés :
- santé: l'effet d'une carence alimentaire (régime) sur la physiologie d'une cellule
- le monde de l'ARN: construisez de l'ARN avec des bases aimantées
- neurosciences: NeuroBioCell, comprendre et observer le fonctionnement des cellules neuronales
- chimie: façonner les molécules pour en faire des micro-machines
- climat: la fresque du climat avec des étudiant-e-s de l'IUT de Schiltigheim
- Physique: l'Année de la Physique avec une exposition de femmes physiciennes
- Comité du Bas-Rhin de La Ligue contre le cancer (Ligue 67): la recherche contre le cancer, L’Agenda scolaire (ma santé, j’en prends soin), comment se protéger du cancer
- Sport dans le cadre des JO2024: Histoire du sport en Alsace

Et des conférences :

Conférence exceptionnelle de Jean-Pierre Sauvage, prix Nobel de chimie 2016

Mercredi 11 octobre à 20h00 : Gymnase Im Sand - Lingolsheim: réservation obligatoire

 

Rencontre-débat avec des sportifs médaillés et un préparateur physique professionnel

Mercredi 4 octobre à 20h00 : Maison des Arts de Lingolsheim "Science et condition physique : les sportifs de haut niveau", avec des sportifs médaillés et un préparateur physique professionnel (rugby, snowboard, tir paralympique) : avec Sylvain Dufour snowboard (Vainqueur de la Coupe du Monde 2014, Médaille d’argent aux Championnats du Monde 2009, 3 participations aux Jeux Olympiques, 4ième au JO d’hiver de 2018); Raphaël Voltz, tir à la carabine (Double vice-champion paralympique aux JO Pékin 2008, médaille d'argent JO Londres 2012, Double champion du monde) ; Romain Ritter, Préparateur physique Strasbourg Alsace Rugby. Animée par le Pr Michel Hasselmann.

 

Comprenez l'apport de la science dans le sport - conférences à la Maison des Arts de Lingolsheim à 20h00 :

  • 3 octobre : "Sport et santé": Cancer et activité physique : Dr Evelyne Lonsdorfer
  • 6 octobre: "Ocytocine : amour, sport et autres addictions sympathiques ...": Pr Marcel Hibert
  • 9 octobre: "Médecine, dopage et sport": Dr John Lenertz
  • 13 octobre: "Sports et Sciences": Créativité, partage et Joie de Vivre: Dr Pierre Antony

 

Rencontre-débat avec des scolaires sur l'histoire du sport en Alsace

Mardi 10 octobre à 14h30 : Avec Denis Jallat > Responsable du Comité de rédaction « histoire » de la revue Sciences sociales et sport. Sébastien Stumpp > Membre du Comité d’histoire des ministères chargés de la Jeunesse et des Sports (CHMJS) Cathy Blanc-Reibel > Ingénieure  CNRS

Pour public scolaire: primaires (CM1/CM2) et collèges - Gymnase Im Sand - Lingolsheim: réservation obligatoire

 

Table-Ronde: Sports, racisme et neuroscience - les comportements racistes dans le sport

Samedi 7 octobre à 14h00 : Gymnase Im Sand – Lingolsheim : avec Odile Rohmer Professeure en psychologie sociale - Jérôme Beauchez Professeur de sociologie et d'anthropologie à l'Université de Strasbourg - Daouada Ba > Président de la commission sport de la LICRA

 

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Actualités du GMGM Focus du GMGM Actualités de l'Équipe Becker Actualités de l'Équipe Friant
news-14807 Mon, 16 Oct 2023 15:09:10 +0200 Bacteria, mitochondria, ribosomes & evolution at the Fête de la Science 2023 /en/news/piece-of-news/bacteria-mitochondria-ribosomes-evolution-at-the-fete-de-la-science-2023 Friday, October 13, 2023 was the school day in the Village des Sciences, at the Palais Universitaire. The MITO team was there to familiarise the "youngest generation of scientists" with bases of cellular and molecular biology. Kids and adults from over 20 Alsatian schools discovered the amazing world of bacteria, mitochondria and ribosomes & their evolutionary journey. They could see (and smell!) real bacteria grown in the lab, play with structures of ribosomes to see how they changed over a billion years of evolution, and study electron microscopy photos to learn to recognise healthy and dysfunctional mitochondria.

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Actualités du GMGM Actualités de l'Équipe Tarassov-Smirnov Focus de l'équipe Tarassov-Smirnov
news-14766 Wed, 04 Oct 2023 14:00:17 +0200 GTPase Era at the heart of ribosome assembly /en/news/piece-of-news/gtpase-era-at-the-heart-of-ribosome-assembly Our comprehensive review on the fascinating ribosome assembly GTPase Era/ERAL1 is out! Gruffaz C & Smirnov A (2023) GTPase Era at the heart of ribosome assembly. Front Mol Biosci 10:1263433

Ribosome biogenesis is a key process in all organisms. It relies on coordinated work of multiple proteins and RNAs, including an array of assembly factors. Among them, the GTPase Era stands out as an especially deeply conserved protein, critically required for the assembly of bacterial-type ribosomes from Escherichia coli to humans. In this review, we bring together and critically analyze a wealth of phylogenetic, biochemical, structural, genetic and physiological data about this extensively studied but still insufficiently understood factor. We do so using a comparative and, wherever possible, synthetic approach, by confronting observations from diverse groups of bacteria and eukaryotic organelles (mitochondria and chloroplasts). The emerging consensus posits that Era intervenes relatively early in the small subunit biogenesis and is essential for the proper shaping of the platform which, in its turn, is a prerequisite for efficient translation. The timing of Era action on the ribosome is defined by its interactions with guanosine nucleotides [GTP, GDP, (p)ppGpp], ribosomal RNA, and likely other factors that trigger or delay its GTPase activity. As a critical nexus of the small subunit biogenesis, Era is subject to sophisticated regulatory mechanisms at the transcriptional, post-transcriptional, and post-translational levels. Failure of these mechanisms or a deficiency in Era function entail dramatic generalized consequences for the protein synthesis and far-reaching, pleiotropic effects on the organism physiology, such as the Perrault syndrome in humans.

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Actualités de l'Équipe Tarassov-Smirnov Publications de l'Équipe Tarassov-Smirnov
news-14747 Wed, 04 Oct 2023 11:00:00 +0200 Invited GMGM seminar: Howard RIEZMAN (University of Geneva) /en/news/piece-of-news/external-seminar-howard-riezman-seminar-room-of-ipcb Chemical biology tools to study lipid metabolism and function Agenda du GMGM news-14728 Thu, 21 Sep 2023 17:04:54 +0200 Our detailed CoLoC-seq protocol is published in Bio-protocol /en/news/piece-of-news/our-detailed-coloc-seq-protocol-is-published-in-bio-protocol Anyone who wants to have a clear & reliable idea about RNA localisation inside/outside membrane-bounded organelles, extracellular vesicles, or viral particles can now use this detailed protocol. It includes all reagents & equipment necessary to perform CoLoC-seq experiments, a step-by-step protocol, and useful tips for data analysis & interpretation! Smirnova AJeandard DSmirnov A (2023) Controlled Level of Contamination Coupled to Deep Sequencing (CoLoC-seq) probes the global localisation topology of organelle transcriptomesBio-protocol 13: e4820

Information on RNA localisation is essential for understanding physiological and pathological processes, such as gene expression, cell reprogramming, host–pathogen interactions, and signalling pathways involving RNA transactions at the level of membrane-less or membrane-bounded organelles and extracellular vesicles. In many cases, it is important to assess the topology of RNA localisation, i.e., to distinguish the transcripts encapsulated within an organelle of interest from those merely attached to its surface. This allows establishing which RNAs can, in principle, engage in local molecular interactions and which are prevented from interacting by membranes or other physical barriers. The most widely used techniques interrogating RNA localisation topology are based on the treatment of isolated organelles with RNases with subsequent identification of the surviving transcripts by northern blotting, qRT-PCR, or RNA-seq. However, this approach produces incoherent results and many false positives. Here, we describe Controlled Level of Contamination coupled to deep sequencing (CoLoC-seq), a more refined subcellular transcriptomics approach that overcomes these pitfalls. CoLoC-seq starts by the purification of organelles of interest. They are then either left intact or lysed and subjected to a gradient of RNase concentrations to produce unique RNA degradation dynamics profiles, which can be monitored by northern blotting or RNA-seq. Through straightforward mathematical modelling, CoLoC-seq distinguishes true membrane-enveloped transcripts from degradable and non-degradable contaminants of any abundance. The method has been implemented in the mitochondria of HEK293 cells, where it outperformed alternative subcellular transcriptomics approaches. It is applicable to other membrane-bounded organelles, e.g., plastids, single-membrane organelles of the vesicular system, extracellular vesicles, or viral particles.

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Actualités de l'Équipe Tarassov-Smirnov Publications de l'Équipe Tarassov-Smirnov
news-14686 Fri, 15 Sep 2023 09:31:51 +0200 New publication by MITO-team /en/news/piece-of-news/new-publication-by-mito-team Targeting of CRISPR-Cas12a crRNAs into human mitochondria BIOCHIMIE

Mitochondrial gene editing holds great promise as a therapeutic approach for mitochondrial diseases caused by mutations in the mitochondrial DNA (mtDNA). Current strategies focus on reducing mutant mtDNA heteroplasmy levels through targeted cleavage or base editing. However, the delivery of editing components into mitochondria remains a challenge. Here we investigate the import of CRISPR-Cas12a system guide RNAs (crRNAs) into human mitochondria and study the structural requirements for this process by northern blot analysis of RNA isolated from nucleases-treated mitoplasts. To investigate whether the fusion of crRNA with known RNA import determinants (MLS) improve its mitochondrial targeting, we added MLS hairpin structures at 3’-end of crRNA and demonstrated that this did not impact crRNA ability to program specific cleavage of DNA in lysate of human cells expressing AsCas12a nuclease. Surprisingly, mitochondrial localization of the fused crRNA molecules was not improved compared to non-modified version, indicating that structured scaffold domain of crRNA can probably function as MLS, assuring crRNA mitochondrial import. Then, we designed a series of crRNAs targeting different regions of mtDNA and demonstrated their ability to program specific cleavage of mtDNA fragments in cell lysate and their partial localization in mitochondrial matrix in human cells transfected with these RNA molecules. We hypothesize that mitochondrial import of crRNAs may depend on their secondary structure/sequence. We presume that imported crRNA allow reconstituting the active crRNA/Cas12a system in human mitochondria, which can contribute to the development of effective strategies for mitochondrial gene editing and potential future treatment of mitochondrial diseases.

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Actualités du GMGM Publications du GMGM Actualités de l'Équipe Tarassov-Smirnov
news-14627 Mon, 04 Sep 2023 21:36:14 +0200 New publication in Nature Genetics /en/news/piece-of-news/nouvelle-publication-dans-nature-genetics Telomere-to-telomere assemblies of 142 strains characterize the genome structural landscape in Saccharomyces cerevisiae.
Samuel O’Donnell, Jia-Xing Yue, Omar Abou Saada, Nicolas Agier, Claudia Caradec, Thomas Cokelaer, Matteo De Chiara, Stéphane Delmas, Fabien Dutreux, Téo Fournier, Anne Friedrich, Etienne Kornobis, Jing Li, Zepu Miao, Lorenzo Tattini, Joseph Schacherer, Gianni Liti, Gilles Fischer.

Pangenomes provide access to an accurate representation of the genetic diversity of species, both in terms of sequence polymorphisms and structural variants (SVs). Here we generated the Saccharomyces cerevisiae Reference Assembly Panel (ScRAP) comprising reference-quality genomes for 142 strains representing the species’ phylogenetic and ecological diversity. The ScRAP includes phased haplotype assemblies for several heterozygous diploid and polyploid isolates. We identified circa (ca.) 4,800 nonredundant SVs that provide a broad view of the genomic diversity, including the dynamics of telomere length and transposable elements. We uncovered frequent cases of complex aneuploidies where large chromosomes underwent large deletions and translocations. We found that SVs can impact gene expression near the breakpoints and substantially contribute to gene repertoire evolution. We also discovered that horizontally acquired regions insert at chromosome ends and can generate new telomeres. Overall, the ScRAP demonstrates the benefit of a pangenome in understanding genome evolution at population scale.

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Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-14625 Mon, 04 Sep 2023 21:27:14 +0200 New publication in collabration /en/news/piece-of-news/nouvelle-publication-en-collabration Copy number variation alters local and global mutational tolerance.
Grace Avecilla, Pieter Spealman, Julia Matthews, Elodie Caudal, Joseph Schacherer, David Gresham.

Copy number variants (CNVs), duplications and deletions of genomic sequences, contribute to evolutionary adaptation but can also confer deleterious effects and cause disease. Whereas the effects of amplifying individual genes or whole chromosomes (i.e., aneuploidy) have been studied extensively, much less is known about the genetic and functional effects of CNVs of differing sizes and structures. Here, we investigated Saccharomyces cerevisiae (yeast) strains that acquired adaptive CNVs of variable structures and copy numbers following experimental evolution in glutamine-limited chemostats. Although beneficial in the selective environment, CNVs result in decreased fitness compared with the euploid ancestor in rich media. We used transposon mutagenesis to investigate mutational tolerance and genome-wide genetic interactions in CNV strains. We find that CNVs increase mutational target size, confer increased mutational tolerance in amplified essential genes, and result in novel genetic interactions with unlinked genes. We validated a novel genetic interaction between different CNVs and BMH1 that was common to multiple strains. We also analyzed global gene expression and found that transcriptional dosage compensation does not affect most genes amplified by CNVs, although gene-specific transcriptional dosage compensation does occur for ∼12% of amplified genes. Furthermore, we find that CNV strains do not show previously described transcriptional signatures of aneuploidy. Our study reveals the extent to which local and global mutational tolerance is modified by CNVs with implications for genome evolution and CNV-associated diseases, such as cancer.

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Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-14618 Mon, 04 Sep 2023 11:40:13 +0200 The MITO team welcomes a new PhD student, Théo Markezic /en/news/piece-of-news/the-mito-team-welcomes-a-new-phd-student-theo-markezic Théo Markezic, funded by IMCBio, starts his PhD studies in the "RNA-binding hubs" group. Théo will work on pervasive and antisense transcription in phylogenetically distant bacteria, E. coli and S. aureus, using experimental evolution approaches. His work will take place in GMGM and IBMC under the supervision of Alexandre Smirnov and Isabelle Caldelari. Théo is funded by IMCBio, via the Inter-Labex PhD programme (MitoCross - NetRNA).

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Actualités de l'Équipe Tarassov-Smirnov
news-13759 Thu, 06 Jul 2023 07:47:41 +0200 Regards sur les ribozymes /en/news/piece-of-news/regards-sur-les-ribozymes Benoït Masquida, directeur de recherche CNRS au laboratoire de Génétique moléculaire, génomique et microbiologie (GMGM) nous explique les multiples facettes des ribozymes, ARN capables d'activité catalytique. Actualités du GMGM Actualités de l'Équipe Becker Focus de l'équipe Becker news-13674 Mon, 19 Jun 2023 13:37:10 +0200 New publication in G3 /en/news/piece-of-news/nouvelle-publication-dans-g3-1 Impact of the acquired subgenome on the transcriptional landscape in Brettanomyces bruxellensis allopolyploids.
Arthur Jallet, Anne Friedrich, Joseph Schacherer.
G3 Genes|Genomes|Genetics. 2023. doi:10.1093/g3journal/jkad115

Gene expression variation can provide an overview of the changes in regulatory networks that underlie phenotypic diversity. Certain evolutionary trajectories such as polyploidization events can have an impact on the transcriptional landscape. Interestingly, the evolution of the yeast species Brettanomyces bruxellensis has been punctuated by diverse allopolyploidization events leading to the coexistence of a primary diploid genome associated with various haploid acquired genomes. To assess the impact of these events on gene expression, we generated and compared the transcriptomes of a set of 87 B. bruxellensis isolates, selected as being representative of the genomic diversity of this species. Our analysis revealed that acquired subgenomes strongly impact the transcriptional patterns and allow discrimination of allopolyploid populations. In addition, clear transcriptional signatures related to specific populations have been revealed. The transcriptional variations observed are related to some specific biological processes such as transmembrane transport and amino acids metabolism. Moreover, we also found that the acquired subgenome causes the overexpression of some genes involved in the production of flavor-impacting secondary metabolites, especially in isolates of the beer population.

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Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-13361 Mon, 17 Apr 2023 09:49:04 +0200 Thesis/postdoctoral fellowship: Dissecting the role of redox signaling in coupling oscillatory metabolism to cell division /en/news/piece-of-news/these-ou-stage-postdoctoral-dissection-du-role-de-la-signalisation-redox-dans-le-couplage-du-metabolisme-oscillatoire-a-la-division-cellulaire A thesis or postdoctoral fellowship funded on an ANR project has just been open in the "Quantitative Biology of Cell Growth". Under specific conditions of growth in a chemostat, yeast cell populations spontaneously synchronize to undergo sustained metabolic oscillations, which appear to be tightly coupled to cell growth and division. This entire oscillatory behavior is referred to as the yeast metabolic cycle (YMC). Intriguingly, our lab and others have recently shown that metabolic oscillations persist in the absence of cell division and even appear to be important in determining cell cycle entry and exit. Furthermore, we have shown that redox signaling is involved in the emergence of stable collective metabolic oscillatory behavior and in the coupling of the oscillatory metabolic state to cell division in the context of YMC. Recent studies reveal the existence of metabolic oscillations, redox signaling, and protein kinase A activity at the single cell level. Consistent with YMC, these oscillations may be coupled to cell division and appear to be important in regulating cell cycle entry and exit, but they may also persist independently of cell division. However, it is unclear whether the metabolic cycles observed at the single cell level correspond to those observed in CMJ-synchronized populations. The mechanistic basis of metabolic cycles in both systems is completely unknown and the exact causal relationships, interference and interaction between metabolic cycles and cell division remain elusive. In this thesis project, we will develop a new methodology that merges population-scale dynamic measurements with single-cell monitoring using microfluidics. By combining our expertise in yeast genetics, novel genetically encoded redox sensors, quantitative live cell imaging, microfluidics and chemostat cultures, we will elucidate population heterogeneity in terms of metabolic cycles and cell division with a spatial and temporal resolution previously unattainable. In addition, we will address the role of redox signaling and protein kinase A activity in coupling cell division with oscillatory metabolism. By combining our approaches with computational analyses, we will take important steps towards deciphering the fundamental principles that govern the emergence of metabolic oscillations, elucidating their potential fitness benefits in fluctuating environments, and understanding their relevance to cell division.

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Actualités de l'Équipe Charvin
news-13359 Mon, 17 Apr 2023 09:18:18 +0200 Thesis/postdoctoral fellowship: Elucidating the scenario of entry into replicative senescence in yeast /en/news/piece-of-news/these-ou-stage-postdoctoral-elucider-le-scenario-dentree-en-senescence-replicative-chez-la-levure A thesis or postdoctoral fellowship funded on an ANR project has just been open in the "Quantitative Biology of Cell Growth".

Budding yeast is a well known model to study aging at the cellular level: a mother cell can perform a limited number of divisions before entering senescence and dying. Despite the identification of many genes that determine replicative longevity, the mechanism that controls the transition to the senescent state remains very poorly understood, in particular, because the high variability between cells prevents deciphering the causal relationships between different markers of aging when working on populations. In this context, we have recently developed a microscopy platform allowing to follow and quantify the dynamics of successive divisions and fluorescent markers in a quantitative way. The goal of the project will be to use this new methodology to classify the order of appearance of senescence markers in a semi-systematic way. Second, we will use specific longevity-extending mutants to determine how they impact the appearance of markers and thus understand the scenario of entry into replicative senescence.

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Actualités de l'Équipe Charvin
news-13357 Mon, 17 Apr 2023 08:24:15 +0200 Théo Aspert was awarded the 2022 SBS thesis prize /en/news/piece-of-news/prix-de-these-2022-de-la-sbs-attribue-a-theo-aspert Théo Aspert was awarded a thesis prize by the Strasbourg Biology Society for his thesis "Deciphering the aging dynamics using microfluidics and deep-learning". Théo defended his thesis in 2022 under the supervision of Gilles Charvin. He presented his works during the cermony which will was held Friday 21st April 2023 from 13:00 to 18:30 in the "Collège Doctoral Européen" amphitheater within the scope of the Journées de L’Ecole Doctorale « Sciences de la Vie et de la Santé » of the Strasbourg University.

DetecDiv, a generalist deep-learning platform for automated cell division tracking and survival analysis

Théo Aspert, Didier Hentsch, Gilles Charvin. eLife, (2022) - DOI: 10.7554/eLife.79519

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Actualités du GMGM Actualités de l'Équipe Charvin
news-13213 Tue, 14 Mar 2023 12:37:19 +0100 Sylvie Friant aux Femin'Days au Lycée Leclerc de Saverne /en/news/piece-of-news/sylvie-friant-aux-femindays-au-lycee-leclerc-de-saverne Actualités du GMGM Actualités de l'Équipe Friant news-13132 Thu, 02 Mar 2023 10:34:51 +0100 Review on the evolutionary aspects of the FinO/ProQ family proteins /en/news/piece-of-news/review-on-the-evolutionary-aspects-of-the-fino-proq-family-proteins Our review paper on the evolutionary significance of RNA-binding proteins of the FinO/ProQ family has been published in Bioscience Reports. FinO/ProQ-family proteins: an evolutionary perspective

Zhen Liao & Alexandre Smirnov

Biosci Rep (2023) 43 (3): BSR20220313

RNA-binding proteins are key actors of post-transcriptional networks. Almost exclusively studied in the light of their interactions with RNA ligands and the associated functional events, they are still poorly understood as evolutionary units. In this review, we discuss the FinO/ProQ family of bacterial RNA chaperones, how they evolve and spread across bacterial populations and what properties and opportunities they provide to their host cells. We reflect on major conserved and divergent themes within the family, trying to understand how the same ancestral RNA-binding fold, augmented with additional structural elements, could yield either highly specialised proteins or, on the contrary, globally acting regulatory hubs with a pervasive impact on gene expression. We also consider dominant convergent evolutionary trends that shaped their RNA chaperone activity and recurrently implicated the FinO/ProQ-like proteins in bacterial DNA metabolism, translation and virulence. Finally, we offer a new perspective in which FinO/ProQ-family regulators emerge as active evolutionary players with both negative and positive roles, significantly impacting the evolutionary modes and trajectories of their bacterial hosts.

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Actualités de l'Équipe Tarassov-Smirnov Publications de l'Équipe Tarassov-Smirnov
news-12988 Wed, 25 Jan 2023 13:58:42 +0100 The MITO team welcomes a new member, Dr Marie SISSLER (CNRS) /en/news/piece-of-news/the-mito-team-welcomes-a-new-member-dr-marie-sissler-cnrs Dr Sissler works on diverse aspects of mitochondrial RNA biology. She is particularly interested in mitochondrial aminoacyl-tRNA synthetases in as diverses biological models as humans and trypanosomatids. Dr Sissler studies the basic principles of their orhanisation and molecular functions as well as their involvement in human pathologies. 

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Actualités de l'Équipe Tarassov-Smirnov
news-12929 Mon, 16 Jan 2023 11:27:48 +0100 New publication in Genome Biology and Evolution /en/news/piece-of-news/nouvelle-publication-dans-genome-biology-and-evolution Contrasting genomic evolution between domesticated and wild Kluyveromyces lactis yeast populations.
Anne Friedrich, Jean-Sébastien Gounot, Andreas Tsouris, Claudine Bleykasten, Kelle Freel, Claudia Caradec, Joseph Schacherer.
Genome Biology and Evolution. 2023. doi:10.1093/gbe/evad004

The process of domestication has variable consequences on genome evolution leading to different phenotypic signatures. Access to the complete genome sequences of a large number of individuals makes it possible to explore the different facets of this domestication process. Here, we sought to explore the genome evolution of Kluyveromyces lactis, a yeast species well-known for its involvement in dairy processes but also present in natural environments. Using a combination of short and long-read sequencing strategies, we investigated the genomic variability of 41 K. lactis isolates and found that the overall genetic diversity of this species is very high (θw = 3.3 × 10−2) compared to other species such as Saccharomyces cerevisiae (θw = 1.6 × 10−2). However, the domesticated dairy population shows a reduced level of diversity (θw = 1 × 10−3), probably due to a domestication bottleneck. In addition, this entire population is characterized by the introgression of the LAC4 and LAC12 genes, responsible for lactose fermentation and coming from the closely related species, Kluyveromyces marxianus, as previously described. Our results also highlighted that the LAC4/LAC12 gene cluster was acquired through multiple and independent introgression events. Finally, we also identified several genes that could play a role in adaptation to dairy environments through copy number variation. These genes are involved in sugar consumption, flocculation and drug resistance, and may play a role in dairy processes. Overall, our study illustrates contrasting genomic evolution and sheds new light on the impact of domestication processes on it.

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Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer
news-12925 Fri, 13 Jan 2023 20:01:45 +0100 New publication in PLoS Genetics /en/news/piece-of-news/nouvelle-publication-dans-plos-genetics Lessons from the meiotic recombination landscape of the ZMM deficient budding yeast Lachancea waltii.
Fabien Dutreux, Abhishek Dutta, Emilien Peltier, Sabrina Bibi-Triki, Anne Friedrich, Bertrand Llorente, Joseph Schacherer.
PLoS Genet. 2023. doi:10.1371/journal.pgen.1010592

Meiotic recombination is a driving force for genome evolution, deeply characterized in a few model species, notably in the budding yeast Saccharomyces cerevisiae. Interestingly, Zip2, Zip3, Zip4, Spo16, Msh4, and Msh5, members of the so-called ZMM pathway that implements the interfering meiotic crossover pathway in S. cerevisiae, have been lost in Lachancea yeast species after the divergence of Lachancea kluyveri from the rest of the clade. In this context, after investigating meiosis in L. kluyveri, we determined the meiotic recombination landscape of Lachancea waltii. Attempts to generate diploid strains with fully hybrid genomes invariably resulted in strains with frequent whole-chromosome aneuploidy and multiple extended regions of loss of heterozygosity (LOH), which mechanistic origin is so far unclear. Despite the lack of multiple ZMM pro-crossover factors in L. waltii, numbers of crossovers and noncrossovers per meiosis were higher than in L. kluyveri but lower than in S. cerevisiae, for comparable genome sizes. Similar to L. kluyveri but opposite to S. cerevisiae, L. waltii exhibits an elevated frequency of zero-crossover bivalents. Lengths of gene conversion tracts for both crossovers and non-crossovers in L. waltii were comparable to those observed in S. cerevisiae and shorter than in L. kluyveri despite the lack of Mlh2, a factor limiting conversion tract size in S. cerevisiae. L. waltii recombination hotspots were not shared with either S. cerevisiae or L. kluyveri, showing that meiotic recombination hotspots can evolve at a rather limited evolutionary scale within budding yeasts. Finally, L. waltii crossover interference was reduced relative to S. cerevisiae, with interference being detected only in the 25 kb distance range. Detection of positive inference only at short distance scales in the absence of multiple ZMM factors required for interference-sensitive crossovers in other systems likely reflects interference between early recombination precursors such as DSBs.

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Actualités du GMGM Publications du GMGM Actualités de l'Équipe Schacherer