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Guichoux, E.

Publications and source records attributed to Guichoux, E..

11 recordsLinked to original sources

Lack of Evidence for Local Adaptation in Risk Tolerance: A Genetic Study in Northern Senegal.

Risk tolerance is influenced by both environmental and genetic factors and may be shaped by local selective pressures in hazardous environments. In Northern Senegal, fishermen from the village of Guet Ndar are chronically exposed to high occupational mortality risk, making this population a potential model for local adaptation to risky environments. In a previous study, we showed that men from this fishing community were less risk-tolerant than men from a nearby farming village, although this difference could not be explained by variation at the DRD4 locus. Here, we investigated whether genetic variants previously associated with general risk tolerance in large genome-wide association studies (GWAS) exhibit signals of local adaptation in these Senegalese populations. We genotyped 44 candidate SNPs in 373 individuals sampled from the risky fishing area and the non-risky farming area. Population genetic analyses revealed extremely low and non-significant differentiation between the two populations (mean FST = 0.0003, p = 0.33), indicating that the two groups are genetically indistinguishable at these loci. Furthermore, none of the candidate SNPs showed a significant association with experimentally measured risk tolerance after correction for multiple testing. These results provide no evidence that local adaptation for risky behavior has occurred, several explanations may account for this negative result.

evolutionary biology↗

Microbiota-gut-brain axis modulation drives glioblastoma progression and therapy resistance

Glioblastoma is a highly aggressive brain tumour with poor prognosis, whose aetiology, progression, and therapeutic resistance remain incompletely understood. While the microbiota-gut-brain axis has emerged as a key regulator of neurological disorders, its role in glioblastoma biology and treatment response is still largely unexplored. Using a clinically relevant immunocompetent murine model combining glioblastoma stem cell implantation, dextran sodium sulfate-induced gut inflammation, and a full Stupp-like therapeutic protocol, we investigated bidirectional gut-brain communication in glioblastoma. Tumour growth and recurrence were monitored by bioluminescence imaging, tumour transcriptomic profiles were analysed by RNA sequencing, and brain and colon tissues were subjected to histological and molecular analyses. Gut microbiota composition was assessed by 16S rRNA sequencing, while systemic metabolites and cytokines were quantified in plasma. Cross-compartment association bioinformatic analyses were performed to correlate multi-organ readouts. Gut inflammation enhanced glioblastoma growth and promoted tumour recurrence following therapy. Tumour progression was associated with increased infiltration of immunosuppressive macrophages, whereas recurrence correlated with elevated oxidative DNA damage. Remarkably, glioblastoma exerted systemic immunomodulatory effects, attenuating intestinal and systemic inflammatory responses, and induced profound remodelling of gut microbiota composition and predicted metabolic function, including enrichment of Akkermansia and depletion of Lactobacillus. Systemic metabolic profiling was investigated as a route of communication within the gut-brain axis and revealed adaptations in DSS-treated mice associated with tumour burden and therapeutic response. Multi-compartment correlation and multivariable association analyses identified specific bacterial genera and circulating metabolites associated with tumour volume, intestinal inflammation, and genomic instability. These findings uncover a dynamic, bidirectional microbiota-gut-brain axis in glioblastoma and identify intestinal inflammation as a critical determinant of tumour progression and therapeutic outcome. Targeting gut disturbances and microbiota-associated metabolic pathways may represent novel strategies to modulate glioblastoma aggressiveness and treatment response.

cancer biology↗

Whole-genome screening for near-diagnostic genetic markers for white oak species identification in Europe

ContextIdentifying species in the European white oak complex has been a long standing concern in taxonomy, evolution, forest research and management. Quercus petraea, Q. robur, Q. pubescens and Q. pyrenaica are part of this species complex in western temperate Europe and hybridize in mixed stands, challenging species identification. AimsOur aim was to identify diagnostic single nucleotide polymorphisms (SNPs) for each of the four species that are suitable for routine use and rapid diagnosis in research and applied forestry. MethodsWe first scanned existing whole-genome and target-capture data sets in a reduced number of samples (training set) to identify candidate diagnostic SNPs, ie genomic positions being characterized by a reference allele in one species and by the alternative allele in all other species. Allele frequencies of the candidates SNPs were then explored in a larger, range-wide sample of populations in each species (validation step). ResultsWe found a subset of 38 SNPs (ten for Q. petraea, seven for Q. pubescens, nine for Q. pyrenaica and twelve for Q. robur) that showed near-diagnostic features across their species distribution ranges with Q. pyrenaica and Q. pubescens exhibiting the highest and lowest diagnosticity, respectively. ConclusionsWe provide a new, efficient and reliable molecular tool for the identification of the species Q. petraea, Q. robur, Q. pubescens and Q. pyrenaica, which can be used as a routine tool in forest research and management. This study highlights the resolution offered by whole-genome sequencing data to design diagnostic marker sets for taxonomic assignment, even for species complexes with relatively low differentiation.

plant biology↗

Sequencing, de novo assembly of Ludwigia plastomes, and comparative analysis within the Onagraceae family

The Onagraceae family, which belongs to the order Myrtales, consists of approximately 657 species and 17 genera, including the genus Ludwigia L., which is comprised of 82 species. There are few genomic resources for Onagraceae, which limits phylogenetic and population genetics, as well as genomic studies. In this study, new complete plastid genomes of Ludwigia grandiflora subps. hexapetala (Lgh) and Ludwigia peploides subsp montevidensis (Lpm) were generated using a combination of different sequencing technologies. These plastomes were then compared to the published Ludwigia octovalvis (Lo) plastid genome, which was re-annotated by the authors. We initially sequenced and assembled the chloroplast (cp) genomes of Lpm and Lgh using a hybrid strategy. We observed the existence of two Lgh haplotypes and two potential Lpm haplotypes. Lgh, Lpm, and Lo plastomes were similar in terms of genome size, gene number, structure, and inverted repeat (IR) boundaries, comparable to other species in the Myrtales order. A total of 45 to 65 SSRs (simple sequence repeats), were detected, depending on the species, with the majority consisting solely of A and T, which is common among angiosperms. Four chloroplast genes (matK, accD, ycf2 and ccsA) were found under positive selection pressure, which is commonly associated with plant development, and especially in aquatic plants such as Lgh, and Lpm. Our hybrid sequencing approach revealed the presence of two Lgh plastome haplotypes which will help to advance phylogenetic and evolutionary studies, not only specifically for Ludwigia, but also the Onagraceae family and Myrtales order. To enhance the robustness of our findings, a larger dataset of chloroplast genomes would be beneficial.

genomics↗

Plant mutations: slaying beautiful hypotheses by surprising evidence

Somatic mutations potentially play a role in plant evolution, but common expectations pertaining to plant somatic mutations remain insufficiently tested. Unlike in most animals, the plant germline is assumed to be set aside late in development, leading to the expectation that plants accumulate somatic mutations along growth. Therefore, several predictions were made on the fate of somatic mutations: mutations have generally low frequency in plant tissues; mutations at high frequency have a higher chance of intergenerational transmission; branching topology of the tree dictates mutation distribution; and, exposure to UV radiation increases mutagenesis. To provide new insights into mutation accumulation and transmission in plants, we produced two high-quality reference genomes and a unique dataset of 60 high-coverage whole-genome sequences of two tropical tree species, Dicorynia guianensis (Fabaceae) and Sextonia rubra (Lauraceae). We identified 15,066 de novo somatic mutations in D. guianensis and 3,208 in S. rubra, surprisingly almost all found at low frequency. We demonstrate that: 1) low-frequency mutations can be transmitted to the next generation; 2) mutation phylogenies deviate from the branching topology of the tree; and 3) mutation rates and mutation spectra are not demonstrably affected by differences in UV exposure. Altogether, our results suggest far more complex links between plant growth, ageing, UV exposure, and mutation rates than commonly thought. Significance StatementThe origin and fate of new mutations have received less attention in plants than in animals. Similarly to animals, plant mutations are expected to accumulate with growth and time, and under exposure to UV light. However, contrary to animals, plant reproductive organs form late in an individuals development, allowing the transmission to the progeny of mutations accumulated along growth. Here, we resequenced DNA from different branches differentially exposed to sunlight of two tropical tree species. We showed that new mutations are generally rare in plant tissues and do not mimic branching patterns but can nevertheless be transmitted to the progeny. Our findings provide a new perspective on heritable plant mutation and its pivotal role as the engine of evolution.

genomics↗

Comparative genomics of Mycoplasma feriruminatoris, a fast-growing pathogen of wild Caprinae

Mycoplasma feriruminatoris is a fast-growing Mycoplasma species isolated from wild Caprinae and first described in 2013. M. feriruminatoris isolates have been associated with arthritis, keratoconjunctivitis, pneumonia and septicemia, but were also recovered from apparently healthy animals. To better understand what defines this species, we performed a genomic survey on 14 strains collected from free-ranging or zoo-housed animals between 1987 and 2017. The average chromosome size of the M. feriruminatoris strains was 1,040 {+/-} 0,024 kbp, with 24% G+C and 852 {+/-} 31 CDS. The core genome and pan-genome of the M. feriruminatoris species contained 628 and 1,312 protein families, respectively. The M. feriruminatoris strains displayed a relatively closed pan-genome, with many features and putative virulence factors shared with species from the M. mycoides cluster, including the MIB-MIP Ig cleavage system, a repertoire of DUF285 surface proteins and a complete biosynthetic pathway for galactan. M. feriruminatoris genomes were found to be mostly syntenic, although repertoires of mobile genetic elements, including Mycoplasma Integrative and Conjugative Elements, insertion sequences, and a single plasmid varied. Phylogenetic- and gene content analyzes confirmed that M. feriruminatoris was closer to the M. mycoides cluster than to the ruminant species M. yeatsii and M. putrefaciens. Ancestral genome reconstruction showed that the emergence of the M. feriruminatoris species was associated with the gain of 17 gene families, some of which encode defense enzymes and surface proteins, and the loss of 25 others, some of which are involved in sugar transport and metabolism. This comparative study suggests that the M. mycoides cluster could be extended to include M. feriruminatoris. We also find evidence that the specific organization and structure of the DnaA boxes around the oriC of M. feriruminatoris may contribute to drive the remarkable fast growth of this minimal bacterium.

microbiology↗

NGS data reveals the phyllosphere microbiome of wheat plants infected by the fungal pathogen Zymoseptoria tritici

The fungal pathogen Zymoseptoria tritici is the causal agent of Septoria tritici blotch (STB), a major wheat disease in Western Europe. Microorganisms inhabiting wheat leaves might act as beneficial, biocontrol or facilitating agents that could limit or stimulate the development of Z. tritici. Improving our understanding of microbial communities in the wheat phyllosphere would lead to new insights into STB management. This resource announcement provides fungal and bacterial metabarcoding datasets obtained by sampling wheat leaves differing in the presence of symptoms caused by Z. tritici. Tissues were sampled from three wheat commercial varieties on three sampling dates during a cropping season. Weeds around wheat fields were sampled as well. In total, more than 450 leaf samples were collected. The pathogen Z. tritici was quantified using qPCR. We provide the raw metabarcoding datasets, the Amplicon Sequence Variant (ASV) tables obtained after bioinformatic processing, the metadata associated to each sample (sampling date, wheat variety and tissue health condition), a preliminary descriptive analysis of the data, and the code used for bioinformatic and descriptive statistical analysis.

microbiology↗

Genetic signatures of divergent selection in European beech (Fagus sylvatica L.) are associated with the variation in temperature and precipitation across its distribution range

High genetic variation and extensive gene flow may help forest trees with adapting to ongoing climate change, yet the genetic bases underlying their adaptive potential remain largely unknown. We investigated range-wide patterns of potentially adaptive genetic variation in 64 populations of European beech (Fagus sylvatica L.) using 270 SNPs from 139 candidate genes involved either in phenology or in stress responses. We inferred neutral genetic structure and processes (drift and gene flow) and performed differentiation outlier analyses and gene-environment association (GEA) analyses to detect signatures of divergent selection. Beech range-wide genetic structure was consistent with the species previously identified postglacial expansion scenario and recolonization routes. Populations showed high diversity and low differentiation along the major expansion routes. A total of 52 loci were found to be putatively under selection and 15 of them turned up in multiple GEA analyses. Temperature and precipitation related variables were equally represented in significant genotype-climate associations. Signatures of divergent selection were detected in the same proportion for stress response and phenology-related genes. The range-wide adaptive genetic structure of beech appears highly integrated, suggesting a balanced contribution of phenology and stress-related genes to local adaptation, and of temperature and precipitation regimes to genetic clines. Our results imply a best-case scenario for the maintenance of high genetic diversity during range shifts in beech (and putatively other forest trees) with a combination of gene flow maintaining within-population neutral diversity and selection maintaining between-population adaptive differentiation.

evolutionary biology↗

Fast sequence-based microsatellite genotyping development workflow for any non-model species

Application of high-throughput sequencing technologies to microsatellite genotyping (SSRseq) has been shown to remove many of the limitations of electrophoresis-based methods and to refine inference of population genetic diversity and structure. We present here a streamlined SSRseq development workflow that includes microsatellite development, multiplexed marker amplification and sequencing, and automated bioinformatics data analysis. We illustrate its application to five groups of species across phyla (fungi, plant, insect and fish) with different levels of genomic resource availability. We found that relying on previously developed microsatellite assay is not optimal and leads to a resulting low number of reliable locus being genotyped. In contrast, de novo ad hoc primer designs gives highly multiplexed microsatellite assays that can be sequenced to produce high quality genotypes for 20 to 40 loci. We highlight critical upfront development factors to consider for effective SSRseq setup in a wide range of situations. Sequence analysis accounting for all linked polymorphisms along the sequence, quickly generates a powerful multi-allelic haplotype-based genotypic dataset, calling to new theoretical and analytical frameworks to extract more information from multi-nucleotide polymorphism marker systems.

genetics↗

Conserved DNA polymorphisms distinguish species in the eastern North American white oak syngameon: Insights from an 80-SNP oak DNA genotyping toolkit

The eastern North American white oaks, a complex of approximately 16 potentially interbreeding species, have become a classic model for studying the genetic nature of species in a syngameon. Genetic work over the past two decades has demonstrated the reality of oak species, but gene flow between sympatric oaks raises the question of whether there are conserved regions of the genome that define oak species. Does gene flow homogenize the entire genome? Do the regions of the genome that distinguish a species in one part of its range differ from the regions that distinguish it in other parts of its range, where it grows in sympatry with different species? Or are there regions of the genome that are relatively conserved across species ranges? In this study, we revisit seven species of the eastern North American white oak syngameon using a set of 80 SNPs selected in a previous study because they show differences among, and consistency within, the species. We test the hypothesis that there exist segments of the genome that do not become homogenized by repeated introgression, but retain distinct alleles characteristic of each species. We undertake a rangewide sampling to investigate whether SNPs that appeared to be fixed based on a relatively small sample in our previous work are fixed or nearly fixed across the range of the species. Each of the seven species remains genetically distinct across its range, given our diagnostic set of markers, with relatively few individuals exhibiting admixture of multiple species. SNPs map back to all 12 Quercus linkage groups (chromosomes) and are separated from each other by an average of 7.47 million base pairs ({+/-} 8.74 million bp, s.d.), but are significantly clustered relative to a random null distribution, suggesting that our SNP toolkit reflects genome-wide patterns of divergence while potentially being concentrated in regions of the genome that reflect a higher-than-average history of among-species divergence. This application of a DNA toolkit designed for the simple problem of identifying species in the field has an important implication: the eastern North American white oak syngameon is composed of entities that most taxonomists would consider \"good species,\" and species in the syngameon retain their genetic cohesion because characteristic portions of the genome do not become homogenized despite a history of introgression.

evolutionary biology↗

High-quality SNPs from genic regions highlight introgression patterns among European white oaks (Quercus petraea and Q. robur).

The Src homology-2 domain containing phosphatase SHP2 is a critical regulator of signal transduction, being implicated in cell growth and differentiation. Activating mutations cause developmental disorders and act as oncogenic drivers in hematologic cancers. SHP2 is activated by phosphopeptide binding to the N-SH2 domain, triggering the release of N-SH2 from the catalytic PTP domain. Based on early crystallographic data, it has been widely accepted that opening of the binding cleft of N-SH2 serves as the key "allosteric switch" driving SHP2 activation. To test the putative coupling between binding cleft opening and SHP2 activation as assumed by the "allosteric switch" model, we critically reviewed structural data of SHP2 and we used extensive molecular dynamics (MD) simulation and free energy calculations of isolated N-SH2 in solution, SHP2 in solution, and SHP2 in a crystal environment. Our results demonstrate that the binding cleft in N-SH2 is constitutively flexible and open in solution, and that a closed cleft found in certain structures is a consequence of crystal contacts. The degree of opening of the binding cleft has only a negligible effect on the free energy of SHP2 activation. Instead, SHP2 activation is greatly favored by the opening of the central {beta}- sheet of N-SH2. We conclude that opening of the N-SH2 binding cleft is not the key allosteric switch triggering SHP2 activation. Significance StatementSHP2 is a multi-domain protein, playing an important role in up-regulating cellular processes such as cell survival, proliferation, and programmed cell death. SHP2 mutations cause developmental disorders and were found in many cancer types, including neuroblastoma, breast cancer, and leukemia. In healthy cells, SHP2 mainly takes an autoinhibited, inactive form, and SHP2 is activated upon binding of phosphopeptides to the N-SH2 domain. For the past two decades, the widening of the binding cleft upon peptide binding has been considered as the key event driving SHP2 activation. Here, by analyzing crystallographic data and molecular simulations, we demonstrate that the binding cleft in N-SH2 is, instead, already open and accessible in solution, and its degree of opening does not influence SHP2 activation.

evolutionary biology↗