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Gautier, V.

Publications and source records attributed to Gautier, V..

13 recordsLinked to original sources

Recombination persists near the mating-type locus in pseudo-homothallic Cladorrhinum fungi (Sordariales)

Recombination suppression has evolved repeatedly across eukaryotes around sex-determining and mating-type loci. Recent theoretical models proposed that such suppression can evolve due to various effects of recessive deleterious mutations, predicting that it should only evolve in lineages experiencing extended diploid phases. Ascomycete fungi provide a powerful system to test this prediction, as pseudo-homothallic ascomycetes maintain prolonged diploid-like phases, while most other ascomycetes have a predominant haploid phase. Megabase-scale non-recombining regions have in fact been reported around the mating-type locus in the four pseudo-homothallic ascomycete lineages studied to date. Here, we studied a previously unexplored lineage of Sordariales, formerly referred to as Podospora australis and suggested to be pseudo-homothallic. Combining genome sequencing, phylogenomic analyses and life-cycle characterization, we identified and described two distinct species and reassigned them to the Cladorrhinum genus. We showed that the two species produce large proportions of self-fertile ascospore-derived mycelia, but the frequencies varied substantially among four strains, and with a selfing progeny, indicating large variation in the extent of the diploid-like phase. By analysing the genomes of five wild strains and of selfing progenies, we did not detect any footprints of large recombination suppression (no heterozygosity, rearrangements or repeated elements). This may be due to the smaller proportion of the life cycle spent in a diploid-like stage compared to other pseudo-homothallic species, or to other features of the life cycle, in agreement with theoretical models. In addition, our results decouple the evolution of pseudo-homothallism from that of recombination suppression, showing that there is no fundamental developmental constraint forcing their joint evolution.

evolutionary biology↗

Genomic and eco-geographic features of locally adapted inversions in wild sunflowers

Chromosomal inversions are increasingly recognized as important drivers of local adaptation and ecological divergence because they suppress recombination and maintain adaptive allele combinations despite ongoing gene flow. However, the eco-evolutionary conditions favouring the establishment of such indirectly adaptive inversions, as well as the genomic features that distinguish them from other inversions remain incompletely understood. In this study, we investigated these questions in a wild sunflower system comprising two species: Helianthus debilis and Helianthus praecox, which exhibit diverse ecotypes and varying degrees of geographic overlap across Texas and Florida in the USA. To resolve the evolutionary relationships between and within these species, and identify potentially adaptive inversions, we generated haplotype-resolved reference assemblies and integrated comparative and population genomic analyses. We identified three major genetic clusters that only partially corresponded to taxonomic classifications. We further detected 156 inversions across the genome, 11 of which showed signatures consistent with a role in local adaptation. Notably, nine of the 11 putatively adaptive inversions were found in sympatric Texas populations. Together with a similar enrichment of inversions in genome assemblies from sympatric versus allopatric populations, our results suggest that inversions are more likely to evolve in heterogeneous environments with ongoing gene flow than in allopatry. Lastly, locally adaptive inversions were generally larger, contained more genes, and showed greater sequence divergence between haplotypes than other types of inversions. Our findings provide empirical support for the role of gene flow in promoting inversion establishment and identify genomic characteristics associated with indirectly adaptive inversions.

evolutionary biology↗

Integrating metagenome-scale metabolic modelling and metabolomics to identify biochemical interactions in Microcystis phycospheres

Favoured by global changes, freshwater cyanobacterial harmful blooms generate major ecological, economical and public health challenges. Microcystis, one of the most widespread cyanobacterial genera, grows within a phycosphere where specialised interactions with its microbiome occur, and are suspected to influence bloom appearance and its potential toxicity. Using a combination of metagenomic, metabolomic and metabolic modelling, we characterised the phycospheres of twelve Microcystis strains isolated from a French pond. The distribution of metabolic reactions within Microcystis was consistent with their genospecies, whereas the metabolic landscape at the community level diverged from cyanobacterial phylogeny indicating functional decoupling between cyanobacteria and their associated microbiomes. Phycosphere-associated bacteria substantially expand the metabolic repertoire of the system, while maintaining functional redundancy within and across communities. On the other hand, metabolomic profiles were largely driven by cyanobacterial metabolic outputs. Metabolic modelling, together with the identification of toxic specialised metabolites produced by specific biosynthetic gene clusters, further highlighted differences in metabolic potential among phycospheres. Together, these findings deepen the understanding of Microcystis phycosphere functioning, demonstrate the value of multi-omics systems biology approaches, and underscore the ecological relevance of interspecies and inter-phycosphere metabolic interactions as a structuring process in bloom-associated microbiomes.

systems biology↗

Stepwise recombination suppression around the mating-type locus associated with a diploid-like life cycle in Schizothecium fungi

Recombination suppression often evolves around sex-determining loci and extends stepwise, resulting in adjacent regions with different levels of divergence between sex chromosomes, called evolutionary strata. In Ascomycota fungi, evolutionary strata have been found around the mating-type (MAT) locus only in pseudo-homothallic species, i.e., with a diploid-like lifecycle and mycelia carrying nuclei of both mating types. In contrast, no recombination suppression has been observed in fungi with a haploid-like lifecycle, such as heterothallic fungi (with mycelial colonies of a single mating type each). Here, we investigated the evolution of recombination suppression in a clade of dung fungi encompassing 16 pseudo-homothallic and three heterothallic sibling species from the Schizothecium genus (Ascomycota, Sordariales). The analysis of genetic divergence based on genome sequencing indicated recombination suppression around the MAT locus in all investigated 13 pseudo-homothallic species. The non-recombining region ranged from 600 kb to 1.6 Mb and harbored multiple evolutionary strata, varying in size and number among species. The separation of alleles associated with alternative mating types in gene genealogies across strains within species, the high linkage disequilibrium and an inversion in one species supported the lack of recombination in the MAT-proximal region in pseudo-homothallic species. The overall lack of trans-specific polymorphism suggested multiple independent events of recombination suppression or the occurrence of rare events of recombination or genic conversion. Progeny analyses showed the occurrence of recombination close to the MAT locus in heterothallic strains. We thus revealed here multiple and likely independent evolutionary strata, associated with an extended diploid-like stage in Schizothecium fungi, which provides a good model for research on sex-related chromosome evolution.

evolutionary biology↗

Huge genetic diversity of Schizothecium tetrasporum (Wint.). N. Lundq.: delimitation of 18 species distributed into three complexes through genome sequencing

Analyses of the genetic diversity of well-studied fungi of the Sordariales order, such as Neurospora spp. and Podospora anserina (syn. Triangularia anserina), have shown that the species classically defined by morphology are often complexes of cryptic species. Here, we report on the species delimitation among 76 strains producing mycelium and sexual reproductive structures identical to those of the pseudo-homothallic Sordariales species Schizothecium tetrasporum (syn. Neoschizothecium tetrasporum). Their whole genomes were sequenced as well as those of six strains closely related to Schizothecium tetrasporum but producing eight-spored asci instead of four-spored ones. The clustering based on the Average Nucleotide Identity (ANI) between the genomes identified eighteen species grouped into three clades, which were further supported by a phylogenetic tree constructed with whole genome Single Nucleotide Polymorphisms (SNPs). Based on their contrasting breeding systems and their large evolutionary distances, we considered the three clades as distinct species complexes. Indeed, two of them, the Schizothecium tetrasporum and Schizothecium pseudotetrasporum complexes, contains pseudo-homothallic species producing four-spored asci, while the third one, which we named Schizothecium octosporum, contains heterothallic species producing eight-spored asci. Surprisingly it was nestled between the two complexes of pseudo-homothallic species. Our data reveals thus a huge genetic diversity of the Schizothecium tetrasporum morpho-species and a convergent evolution of pseudo-homothallism or reversion to heterothallism within the complexes. An epitype for Schizothecium tetrasporum sensus stricto is defined and the seventeen new Schizothecium species are formally described.

microbiology↗

High-quality genome assemblies of four members of the Podospora anserina species complex

The filamentous fungus Podospora anserina is a model organism used extensively in the study of molecular biology, senescence, prion biology, meiotic drive, mating-type chromosome evolution, and plant biomass degradation. It has recently been established that P. anserina is a member of a complex of seven, closely related species. In addition to P. anserina, high-quality genomic resources are available for two of these taxa. Here we provide chromosome-level annotated assemblies of the four remaining species of the complex, as well as a comprehensive dataset of annotated assemblies from a total of 28 Podospora genomes. We find that all seven species have genomes of around 35 Mbp arranged in seven chromosomes that are mostly collinear and less than 2% divergent from each other at genic regions. We further attempt to resolve their phylogenetic relationships, finding significant levels of phylogenetic conflict as expected from a rapid and recent diversification. SignificanceHere we provide a dataset of 28 annotated genomes from the P. anserina species complex, including chromosome-level assemblies of four species that lacked a reference genome. With this dataset in hand, biologists can take advantage of the molecular tools available for P. anserina to study evolutionary dynamics at the interphase between micro- and macroevolution, with particular emphasis on trait evolution, genome architecture, and speciation.

genomics↗

First Eurasian cases of SARS-CoV-2 seropositivity in a free-ranging urban population of wild fallow deer

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects wildlife. Recent studies highlighted that variants of concern (VOC) may expand into novel animal reservoirs with the potential for reverse zoonosis. North American white-tailed deer are the only deer species in which SARS-CoV-2 has been documented, raising the question whether further reservoir species exist as new VOC emerge. Here, we report the first cases of deer SARS-CoV-2 seropositivity in Eurasia, in a city population of fallow deer in Dublin, Ireland. Deer were seronegative in 2020 (circulating variant in humans: Alpha), one animal was seropositive in 2021 (Delta variant), and 57% of animals tested in 2022 were seropositive (Omicron variant). Ex vivo, a clinical isolate of Omicron BA.1 infected fallow deer precision cut lung slice type-2 pneumocytes, also a major target of infection in human lungs. Our findings suggest a change in host tropism as new variants emerged in the human reservoir, highlighting the importance of continued wildlife disease monitoring and limiting human-wildlife contacts. Teaser: This study is the first report of SARS-CoV-2 seropositivity in fallow deer, highlighting expansion of viral variants into new host reservoirs.

microbiology↗

A novel antiviral formulation inhibits SARS-CoV-2 infection of human bronchial epithelium

A novel proprietary formulation, ViruSAL, has previously been demonstrated to inhibit diverse enveloped viral infections in vitro and in vivo. We evaluated the ability of ViruSAL to inhibit SARS-CoV-2 infectivity, using physiologically relevant models of the human bronchial epithelium, to model early infection of the upper respiratory tract. ViruSAL potently inhibited SARS-CoV-2 infection of human bronchial epithelial cells cultured as an air-liquid interface (ALI) model, in a concentration- and time-dependent manner. Viral infection was completely inhibited when ViruSAL was added to bronchial airway models prior to infection. Importantly, ViruSAL also inhibited viral infection when added to ALI models post-infection. No evidence of in vitro cellular toxicity was detected in ViruSAL treated cells at concentrations that completely abrogated viral infectivity. Moreover, intranasal instillation of ViruSAL to a rat model did not result in any toxicity or pathological changes. Together these findings highlight the potential for ViruSAL as a novel and potent antiviral for use within clinical and prophylactic settings.

pharmacology and toxicology↗

Stepwise recombination suppression around the mating-type locus in the fungus Schizothecium tetrasporum (Ascomycota, Sordariales)

Recombination is often suppressed at sex-determining loci in plants and animals, and at self-incompatibility or mating-type loci in plants and fungi. In fungal ascomycetes, recombination suppression around the mating-type locus is associated with pseudo-homothallism, i.e., the production of self-fertile dikaryotic sexual spores carrying the two opposite mating types. This has been well studied in two species complexes from different families of Sordariales: Podospora anserina and Neurospora tetrasperma. However, it is unclear whether this intriguing convergent association holds in other species. We show here that Schizothecium tetrasporum, a fungus from a third family in the order Sordariales, also produces mostly self-fertile dikaryotic spores carrying the two opposite mating types. This was due to a high frequency of second meiotic division segregation at the mating-type locus, indicating the occurrence of a single and systematic crossing-over event between the mating-type locus and the centromere, as in P. anserina. The mating-type locus has the typical Sordariales organization, plus a MAT1-1-1 pseudogene in the MAT1-2 haplotype. High-quality genome assemblies of opposite mating types and segregation analyses revealed a suppression of recombination in a region of 1.3 Mb around the mating-type locus. We detected three evolutionary strata, displaying a stepwise extension of recombination suppression, but no rearrangement or transposable element accumulation in the non-recombining region. Our findings indicate a convergent evolution of self-fertile dikaryotic sexual spores across multiple ascomycete fungi. The particular pattern of meiotic segregation at the mating-type locus was associated with recombination suppression around this locus, that had extended stepwise. This association is consistent with a recently proposed mechanism of deleterious allele sheltering through recombination suppression around a permanently heterozygous locus. AUTHOR SUMMARYRecombination allows faster adaptation and the purging of deleterious mutation but is often paradoxically lacking in sex chromosomes. It has been recently recognized that recombination can also be suppressed on fungal mating-type chromosomes, but the evolutionary explanation and the proximal mechanism of this phenomenon remain unclear. By studying here the sexual biology of a poorly studied mold living in rabbit dung, we reveal a striking convergence in three distant fungal lineages of an independently evolved association between the production of self-fertile sexual spores (carrying two nuclei with opposite mating types), a particular segregation of the mating-type locus and the lack of recombination on mating-type chromosomes, having evolved stepwise. Such a convergent association suggests causal relationships and will contribute to unveil the evolutionary causes of recombination suppression. Graphical summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=174 SRC="FIGDIR/small/500756v2_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1cea706org.highwire.dtl.DTLVardef@378c41org.highwire.dtl.DTLVardef@d90297org.highwire.dtl.DTLVardef@1391c74_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

The genomics of linkage drag in sunflower

Crop wild relatives represent valuable sources of alleles for crop improvement, including adaptation to climate change and emerging diseases. However, introgressions from wild relatives might have deleterious effects on desirable traits, including yield, due to linkage drag. Here we comprehensively analyzed the genomic and phenotypic impacts of wild introgressions into cultivated sunflower to estimate the impacts of linkage drag. First, we generated new reference sequences for seven cultivated and one wild sunflower genotype, as well as improved assemblies for two additional cultivars. Next, relying on previously generated sequences from wild donor species, we identified introgressions in the cultivated reference sequences, as well as the sequence and structural variants they contain. We then used a ridge regression model to test the effects of the introgressions on phenotypic traits in the cultivated sunflower association mapping population. We found that introgression has introduced substantial sequence and structural variation into the cultivated sunflower gene pool, including > 3,000 new genes. While introgressions reduced genetic load at protein-coding sequences and positively affected traits associated with abiotic stress resistance, they mostly had negative impacts on yield and quality traits. Introgressions found at high frequency in the cultivated gene pool had larger effects than low frequency introgressions, suggesting that the former likely were targeted by artificial selection. Also, introgressions from more distantly related species were more likely to be maladaptive than those from the wild progenitor of cultivated sunflower. Thus, pre-breeding efforts should focus, as far as possible, on closely related and fully compatible wild relatives.

genomics↗

An ancient truncated duplication of the anti-Mullerian hormone receptor type 2 gene is a potential conserved master sex determinant in the Pangasiidae catfish family

The evolution of sex determination (SD) mechanisms in teleost fishes is amazingly dynamic, as reflected by the variety of different master sex-determining genes identified, even sometimes among closely related species. Pangasiids are a group of economically important catfishes in many South-Asian countries, but little is known about their sex determination system. Here, we generated novel genomic resources for 12 Pangasiid species and provided a first characterization of their SD system. Based on an Oxford Nanopore long-read chromosome-scale high quality genome assembly of the striped catfish Pangasianodon hypophthalmus, we identified a duplication of the anti-Mullerian hormone receptor type II gene (amhr2), which was further characterized as being sex-linked in males and expressed only in testicular samples. These first results point to a male-specific duplication on the Y chromosome (amhr2by) of the autosomal amhr2a. Sequence annotation revealed that the P. hypophthalmus Amhr2by is truncated in its N-terminal domain, lacking the cysteine-rich extracellular part of the receptor that is crucial for ligand binding, suggesting a potential route for its neofunctionalization. Short-read genome sequencing and reference-guided assembly of 11 additional Pangasiid species, along with sex-linkage studies, revealed that this truncated amhr2by duplication is also conserved as a male-specific gene in many Pangasiids. Reconstructions of the amhr2 phylogeny suggested that amhr2by arose from an ancient duplication / insertion event at the root of the Siluroidei radiation that is dated around 100 million years ago. Altogether these results bring multiple lines of evidence supporting that amhr2by is an ancient and conserved master sex-determining gene in Pangasiid catfishes, a finding that highlights the recurrent usage of the transforming growth factor {beta} pathway in teleost sex determination and brings another empirical case towards the understanding of the dynamics or stability of sex determination systems.

genomics↗

Novel Role of UHRF1 in DNA methylation-mediated repression of latent HIV-1

The multiplicity, heterogeneity and dynamic nature of HIV-1 latency mechanisms are reflected in the current lack of functional cure for HIV-1 and in the various reported ex vivo potencies of latency- reversing agents. Here, we investigated the molecular mechanisms underlying the potency of the DNA methylation inhibitor 5-aza-2-deoxycytidine (5-AzadC) in HIV-1 latency reversal. Doing so, we uncovered specific demethylation CpG signatures induced by 5-AzadC in the HIV-1 promoter. By analyzing the binding modalities to these CpG, we revealed the recruitment of the epigenetic integrator UHRF1 to the HIV-1 promoter. We further demonstrated the role of UHRF1 in DNA methylation- mediated silencing of the latent HIV-1 promoter. As a proof-of-concept to this molecular characterization, we showed that pharmacological downregulation of UHRF1 in ex vivo HIV+ patient cell cultures resulted in potent reactivation of latent HIV-1. Together, we identify UHRF1 as a novel actor in HIV-1 gene silencing and highlight that it constitutes a new molecular target for HIV-1 curative strategies.

microbiology↗

Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage

HIV-1 latency generates reservoirs that prevent viral eradication by the current therapies. To find strategies toward an HIV cure, detailed understandings of the molecular mechanisms underlying establishment and persistence of the reservoirs are needed. The cellular transcription factor KAP1 is known as a potent repressor of gene transcription. Here we report that KAP1 represses HIV-1 gene expression in myeloid cells including microglial cells, the major reservoir of the central nervous system. Mechanistically, KAP1 interacts and colocalizes with the viral transactivator Tat to promote its degradation via the proteasome pathway and repress HIV-1 gene expression. In myeloid models of latent HIV-1 infection, the depletion of KAP1 increased viral gene elongation and reactivated HIV-1 expression. Bound to the latent HIV-1 promoter, KAP1 associates and cooperates with CTIP2, a key epigenetic silencer of HIV-1 expression in microglial cells. In addition, Tat and CTIP2 compete for KAP1 binding suggesting a dynamic modulation of the KAP1 cellular partners upon HIV-1 infection. Altogether, our results suggest that KAP1 contributes to the establishment and the persistence of HIV-1 latency in myeloid cells.

molecular biology↗