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In order to help promote instructional change at French-speaking universities in Europe, we initiated a series of 1-day events centered on learning innovations. Since 2015, these events have been taking place every 6 months at the Université Paris Descartes, with the moral support of three learned scientific societies, the French Academy of Sciences, and sponsoring by leaders in textbook editing and classroom technologies. Each event gathers ~ 40 participants (faculty members, postdocs, and educational specialists) from four countries (Belgium, France, Luxemburg, Switzerland) and invitees, who share their active learning practices, flipped classroom variations representing the most popular strategy. Their experience revealed that faculty who invest themselves in revamping teaching are still isolated at their institutions, although institutional and national support have now been gaining momentum. In particular, the role of educational specialists (known as "ingénieurs pédagogiques" in France) is key to help faculty move away from lecturing. Overall, our event series illustrates that a hands-off approach is effective to foster a cross-border community of committed academics in a context where the process of changing the way we teach at universities is still in its infancy.

The influence of duplicated sequences on chromosomal stability is poorly understood. To characterize chromosomal rearrangements involving duplicated sequences, we compared the organization of tandem repeats of the DUP240 gene family in 15 Saccharomyces cerevisiae strains of various origins. The DUP240 gene family consists of 10 members of unknown function in the reference strain $288C. Five DUP240 paralogs on chromosome I and two on chromosome VII are arranged as tandem repeats that are highly polymorphic in copy number and sequence. We characterized DNA sequences that are likely involved in homologous or nonhomologous recombination events and are responsible for intra-and interchromosomal rearrangements that cause the creation and disappearance of DUP240 paralogs. The tandemly repeated DUP240 genes seem to be privileged sites of gene birth and death.

Author(s): Bernard Dujon (corresponding author) [1]; David Sherman [5, 6]; Gilles Fischer [1]; Pascal Durrens [6, 7]; Serge Casaregola [8]; Ingrid Lafontaine [1]; Jacky de Montigny [9]; Christian Marck [10]; [...]

Abstract Background Gross chromosomal rearrangements (GCRs) such as aneuploidy are key factors in genome evolution as well as being common features of human cancer. Their role in tumour initiation and progression has not yet been completely elucidated and the effects of additional chromosomes in cancer cells are still unknown. Most previous studies in which Saccharomyces cerevisiae has been used as a model for cancer cells have been carried out in the haploid context. To obtain new insights on the role of ploidy, the cellular effects of GCRs were compared between the haploid and diploid contexts. Results A total number of 21 haploid and diploid S. cerevisiae strains carrying various types of GCRs (aneuploidies, nonreciprocal translocations, segmental duplications and deletions) were studied with a view to determining the effects of ploidy on the cellular responses. Differences in colony and cell morphology as well as in the growth rates were observed between mutant and parental strains. These results suggest that cells are impaired physiologically in both contexts. We also investigated the variation in genomic expression in all the mutants. We observed that gene expression was significantly altered. The data obtained here clearly show that genes involved in energy metabolism, especially in the tricarboxylic acid cycle, are up-regulated in all these mutants. However, the genes involved in the composition of the ribosome or in RNA processing are down-regulated in diploids but up-regulated in haploids. Over-expression of genes involved in the regulation of the proteasome was found to occur only in haploid mutants. Conclusion The present comparisons between the cellular responses of strains carrying GCRs in different ploidy contexts bring to light two main findings. First, GCRs induce a general stress response in all studied mutants, regardless of their ploidy. Secondly, the ploidy context plays a crucial role in maintaining the stoichiometric balance of the proteins: the translation rates decrease in diploid strains, whereas the excess protein synthesized is degraded in haploids by proteasome activity.

Abstract Background This paper describes an efficient in silico method for detecting tandem gene arrays (TGAs) in fully sequenced and compact genomes such as those of prokaryotes or unicellular eukaryotes. The originality of this method lies in the search of protein sequence similarities in the vicinity of each coding sequence, which allows the prediction of tandem duplicated gene copies independently of their functionality. Results Applied to nine hemiascomycete yeast genomes, this method predicts that 2% of the genes are involved in TGAs and gene relics are present in 11% of TGAs. The frequency of TGAs with degenerated gene copies means that a significant fraction of tandem duplicated genes follows the birth-and-death model of evolution. A comparison of sequence identity distributions between sets of homologous gene pairs shows that the different copies of tandem arrayed paralogs are less divergent than copies of dispersed paralogs in yeast genomes. It suggests that paralogs included in tandem structures are more recent or more subject to the gene conversion mechanism than other paralogs. Conclusion The method reported here is a useful computational tool to provide a database of TGAs composed of functional or nonfunctional gene copies. Such a database has obvious applications in the fields of structural and comparative genomics. Notably, a detailed study of the TGA catalog will make it possible to tackle the fundamental questions of the origin and evolution of tandem gene clusters.

Abstract Background Chromosomal rearrangements such as duplications and deletions are key factors in evolutionary processes because they promote genomic plasticity. Although the genetic variations in the Saccharomyces cerevisiae species have been well documented, there is little known to date about the impact of the genetic background on the appearance of rearrangements. Results Using the same genetic screening, the type of rearrangements and the mutation rates observed in the S288c S. cerevisiae strain were compared to previous findings obtained in the FL100 background. Transposon-associated rearrangements, a major chromosomal rearrangement event selected in FL100, were not detected in S288c. The mechanisms involved in the occurrence of deletions and duplications in the S288c strain were also tackled, using strains deleted for genes implicated in homologous recombination (HR) or non-homologous end joining (NHEJ). Our results indicate that an Yku80p-independent NHEJ pathway is involved in the occurrence of these rearrangements in the S288c background. Conclusion The comparison of two different S. cerevisiae strains, FL100 and S288c, allowed us to conclude that intra-species genomic variations have an important impact on the occurrence of chromosomal rearrangement and that this variability can partly be explained by differences in Ty1 retrotransposon activity.

In order to help promote instructional change at French‐speaking universities in Europe, we initiated a series of 1‐day events centered on learning innovations. Since 2015, these events have been taking place every 6 months at the Université Paris Descartes, with the moral support of three learned scientific societies, the French Academy of Sciences, and sponsoring by leaders in textbook editing and classroom technologies. Each event gathers ~ 40 participants (faculty members, postdocs, and educational specialists) from four countries (Belgium, France, Luxemburg, Switzerland) and invitees, who share their active learning practices, flipped classroom variations representing the most popular strategy. Their experience revealed that faculty who invest themselves in revamping teaching are still isolated at their institutions, although institutional and national support have now been gaining momentum. In particular, the role of educational specialists (known as ingénieurs pédagogiques in France) is key to help faculty move away from lecturing. Overall, our event series illustrates that a hands‐off approach is effective to foster a cross‐border community of committed academics in a context where the process of changing the way we teach at universities is still in its infancy. © 2019 International Union of Biochemistry and Molecular Biology, 47(5):599–606, 2019. [ABSTRACT FROM AUTHOR]

Species within the human pathogenic Cryptococcus species complex are major threats to public health, causing approximately 1 million infections globally annually. Cryptococcus amylolentus is the most closely known related species of the pathogenic Cryptococcus species complex, and it is non-pathogenic. Additionally, while pathogenic Cryptococcus species have bipolar mating systems with a single large mating type (MAT) locus that represents a derived state in Basidiomycetes, C. amylolentus has a tetrapolar mating system with 2 MAT loci (P/R and HD) located on different chromosomes. Thus, studying C. amylolentus will shed light on the transition from tetrapolar to bipolar mating systems in the pathogenic Cryptococcus species, as well as its possible link with the origin and evolution of pathogenesis. In this study, we sequenced, assembled, and annotated the genomes of 2 C. amylolentus isolates, CBS6039 and CBS6273, which are sexual and interfertile. Genome comparison between the 2 C. amylolentus isolates identified the boundaries and the complete gene contents of the P/R and HD MAT loci. Bioinformatic and chromatin immunoprecipitation sequencing (ChIP-seq) analyses revealed that, similar to those of the pathogenic Cryptococcus species, C. amylolentus has regional centromeres (CENs) that are enriched with species-specific transposable and repetitive DNA elements. Additionally, we found that while neither the P/R nor the HD locus is physically closely linked to its centromere in C. amylolentus, and the regions between the MAT loci and their respective centromeres show overall synteny between the 2 genomes, both MAT loci exhibit genetic linkage to their respective centromere during meiosis, suggesting the presence of recombinational suppressors and/or epistatic gene interactions in the MAT-CEN intervening regions. Furthermore, genomic comparisons between C. amylolentus and related pathogenic Cryptococcus species provide evidence that multiple chromosomal rearrangements mediated by intercentromeric recombination have occurred during descent of the 2 lineages from their common ancestor. Taken together, our findings support a model in which the evolution of the bipolar mating system was initiated by an ectopic recombination event mediated by similar repetitive centromeric DNA elements shared between chromosomes. This translocation brought the P/R and HD loci onto the same chromosome, and further chromosomal rearrangements then resulted in the 2 MAT loci becoming physically linked and eventually fusing to form the single contiguous MAT locus that is now extant in the pathogenic Cryptococcus species. [ABSTRACT FROM AUTHOR]

The numerous yeast genome sequences presently available provide a rich source of information for functional as well as evolutionary genomics but unequally cover the large phylogenetic diversity of extant yeasts. We present here the complete sequence of the nuclear genome of the haploid-type strain of Kuraishia capsulata (CBS1993T), a nitrate-assimilating Saccharomycetales of uncertain taxonomy, isolated from tunnels of insect larvae underneath coniferous barks and characterized by its copious production of extracellular polysaccharides. The sequence is composed of seven scaffolds, one per chromosome, totaling 11.4 Mb and containing 6,029 protein-coding genes, ∼13.5% of which being interrupted by introns. This GC-rich yeast genome (45.7%) appears phylogenetically related with the few other nitrate-assimilating yeasts sequenced so far, Ogataea polymorpha, O. parapolymorpha, and Dekkera bruxellensis, with which it shares a very reduced number of tRNA genes, a novel tRNA sparing strategy, and a common nitrate assimilation cluster, three specific features to this group of yeasts. Centromeres were recognized in GC-poor troughs of each scaffold. The strain bears MAT alpha genes at a single MAT locus and presents a significant degree of conservation with Saccharomyces cerevisiae genes, suggesting that it can perform sexual cycles in nature, although genes involved in meiosis were not all recognized. The complete absence of conservation of synteny between K. capsulata and any other yeast genome described so far, including the three other nitrate-assimilating species, validates the interest of this species for long-range evolutionary genomic studies among Saccharomycotina yeasts. [ABSTRACT FROM AUTHOR]

Abstract: We report the early phase of yeast comparative genomics conducted by a group of seven French CNRS laboratories: the Génolevures Consortium. This first multispecies comparison of Hemiascomycetes (now called Saccharomycotina) opened the way to yeast evolutionary genomics. This analysis indicates that yeasts are powerful organisms to decipher the different mechanisms acting to reshape the genome of eukaryotes during long evolution periods. This initial DNA approach reveals how biodiversity could be characterized with robust data. [Copyright &y& Elsevier]

Transposable element (TE) evolution in genomes has mostly been deduced from comparative genome analyses. TEs often account for a large proportion of the eukaryotic nuclear genome (up to 50%, depending on the species). Among the many existing genomic copies, only a small fraction may contribute to the mobility of a TE family. We have identified here, using a genetic screening procedure to trap Ty1 long terminal repeat-retrotransposon insertions in Saccharomyces cerevisiae, which among the populations of resident Ty1 copies are responsible for Ty1 mobility. Although the newly inserted Ty1 copies resulting from a single round of transposition were found to originate from a limited subset of Ty1 resident copies, they showed a high degree of diversity at the nucleotide level, mainly due to the reverse transcription-mediated recombination. In this process, highly expressed and strikingly nonautonomous mutant Ty1 were found to be the most frequently used resident copies, which suggests that nonautonomous elements play a key role in the dynamics of the Ty1 family. [ABSTRACT FROM AUTHOR]

Background: This paper describes an efficient in silico method for detecting tandem gene arrays (TGAs) in fully sequenced and compact genomes such as those of prokaryotes or unicellular eukaryotes. The originality of this method lies in the search of protein sequence similarities in the vicinity of each coding sequence, which allows the prediction of tandem duplicated gene copies independently of their functionality. Results: Applied to nine hemiascomycete yeast genomes, this method predicts that 2% of the genes are involved in TGAs and gene relics are present in 11% of TGAs. The frequency of TGAs with degenerated gene copies means that a significant fraction of tandem duplicated genes follows the birth-and-death model of evolution. A comparison of sequence identity distributions between sets of homologous gene pairs shows that the different copies of tandem arrayed paralogs are less divergent than copies of dispersed paralogs in yeast genomes. It suggests that paralogs included in tandem structures are more recent or more subject to the gene conversion mechanism than other paralogs. Conclusion: The method reported here is a useful computational tool to provide a database of TGAs composed of functional or nonfunctional gene copies. Such a database has obvious applications in the fields of structural and comparative genomics. Notably, a detailed study of the TGA catalog will make it possible to tackle the fundamental questions of the origin and evolution of tandem gene clusters. [ABSTRACT FROM AUTHOR]

Here, we report the complete nucleotide sequence of the 39 107-bp mitochondrial genome of the yeast Pichia sorbitophila. This genome is closely related to those of Candida parapsilosis and Debaryomyces hansenii, as judged from sequence similarities and synteny conservation. It encodes three subunits of cytochrome oxidase ( COX1, COX2 and COX3), three subunits of ATP synthase ( ATP6, ATP8 and ATP9), the seven subunits of NADH dehydrogenase ( NAD1-6 and NAD4L), the apocytochrome b ( COB), the large and small rRNAs and a complete set of tRNAs. Although the mitochondrial genome of P. sorbitophila contains the same core of mitochondrial genes observed in the ascomycetous yeasts, those coding for the RNAse P and the ribosomal protein VAR1p are missing. Moreover, the mtDNA of P. sorbitophila contains several introns in its genes and has the particularity of possessing an intron, which is not linked to any upstream exon. [ABSTRACT FROM AUTHOR]

Background: Chromosomal rearrangements such as duplications and deletions are key factors in evolutionary processes because they promote genomic plasticity. Although the genetic variations in the Saccharomyces cerevisiae species have been well documented, there is little known to date about the impact of the genetic background on the appearance of rearrangements. Results: Using the same genetic screening, the type of rearrangements and the mutation rates observed in the S288c S. cerevisiae strain were compared to previous findings obtained in the FL100 background. Transposon-associated rearrangements, a major chromosomal rearrangement event selected in FL100, were not detected in S288c. The mechanisms involved in the occurrence of deletions and duplications in the S288c strain were also tackled, using strains deleted for genes implicated in homologous recombination (HR) or non-homologous end joining (NHEJ). Our results indicate that an Yku80p-independent NHEJ pathway is involved in the occurrence of these rearrangements in the S288c background. Conclusion: The comparison of two different S. cerevisiae strains, FL100 and S288c, allowed us to conclude that intra-species genomic variations have an important impact on the occurrence of chromosomal rearrangement and that this variability can partly be explained by differences in Ty1 retrotransposon activity. [ABSTRACT FROM AUTHOR]

Background: The S. cerevisiae carbamylphosphate synthetase -- aspartate transcarbamylase multifunctional protein catalyses the first two reactions of the pyrimidine pathway. In this organism, these two reactions are feedback inhibited by the end product UTP. In the present work, the mechanisms of these integrated inhibitions were studied. Results: The results obtained show that the inhibition is competitive in the case of carbamylphosphate synthetase and non-competitive in the case of aspartate transcarbamylase. They also identify the substrate whose binding is altered by this nucleotide and the step of the carbamylphosphate synthetase reaction which is inhibited. Furthermore, the structure of the domains catalyzing these two reactions were modelled in order to localize the mutations which, specifically, alter the aspartate transcarbamylase sensitivity to the feedback inhibitor UTP. Taken together, the results make it possible to propose a model for the integrated regulation of the two activities of the complex. UTP binds to a regulatory site located in the vicinity of the carbamylphosphate synthetase catalytic subsite which catalyzes the third step of this enzyme reaction. Through a local conformational change, this binding decreases, competitively, the affinity of this site for the substrate ATP. At the same time, through a long distance signal transmission process it allosterically decreases the affinity of the aspartate transcarbamylase catalytic site for the substrate aspartate. Conclusion: This investigation provides informations about the mechanisms of allosteric inhibition of the two activities of the CPSase-ATCase complex. Although many allosteric monofunctional enzymes were studied, this is the first report on integrated allosteric regulation in a multifunctional protein. The positions of the point mutations which specifically abolish the sensitivity of aspartate transcarbamylase to UTP define an interface between the carbamylphosphate synthetase and aspartate transcarbamylase domains, through which the allosteric signal for the regulation of aspartate transcarbamylase must be propagated. [ABSTRACT FROM AUTHOR]