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Biology subjects

Chollet, S.

Publications and source records attributed to Chollet, S..

6 recordsLinked to original sources

Climate drives plasticity and genetic adaptation in apple trees

BackgroundPerennial crops respond to climate change through phenotypic plasticity and local adaptation, yet how these responses are orchestrated at the molecular level and reshaped by domestication remains poorly understood. ResultsWe grew 1,249 seedlings from five populations of M. domestica, M. orientalis, and M. sylvestris under four simulated European climates, quantified 12 phenotypic traits, performed RNA sequencing on 96 individuals, and integrated these data with previously published genome-wide polymorphism data from M. sylvestris to disentangle conserved climate responses from local adaptation. Climate was the dominant driver of phenotypic and transcriptional variation, revealing 344 conserved climate-responsive genes enriched for stress responses, nutrient metabolism, and cell wall biosynthesis. These genes are under strong purifying selection and carry fewer deleterious mutations. In contrast, genome-environment association analyses identified 217 loci associated with temperature and precipitation gradients, only a subset of which showed climate-responsive expression and elevated genomic differentiation. Population-level expression divergence closely mirrored neutral genetic differentiation, indicating that most transcriptomic divergence reflects demographic history rather than adaptive regulatory evolution. Domestication reshaped molecular diversity and mutation load without disrupting the conserved climate-response program. ConclusionsClimate responses in apple are primarily mediated by an evolutionarily conserved transcriptional program maintained by strong purifying selection, whereas local adaptation relies on largely distinct, population-specific loci. These findings reveal that conserved plasticity constitutes the dominant molecular response to climatic variation, whereas local adaptation contributes a secondary, population-specific layer of evolutionary change.

evolutionary biology↗

Uridine-sensitized screening identifies genes and metabolic regulators of nucleotide synthesis

Nucleotides are essential for nucleic acid synthesis, signaling, and metabolism, and can be synthesized de novo or through salvage. Rapidly proliferating cells require large amounts of nucleotides, making nucleotide metabolism a widely exploited target for cancer therapy. However, resistance frequently emerges, highlighting the need for a deeper understanding of nucleotide regulation. Here, we harness uridine salvage and CRISPR-Cas9 screening to reveal regulators of de novo pyrimidine synthesis. We identify several factors and report that pyrimidine synthesis can continue in the absence of coenzyme Q (CoQ), the canonical electron acceptor in de novo synthesis. We further investigate NUDT5 and report its conserved interaction with PPAT, the rate-limiting enzyme in purine synthesis. We show that in the absence of NUDT5, hyperactive purine synthesis siphons the phosphoribosyl pyrophosphate (PRPP) pool at the expense of pyrimidine synthesis, promoting resistance to chemotherapy. Intriguingly, the interaction between NUDT5 and PPAT appears to be disrupted by PRPP, highlighting intricate allosteric regulation. Our findings reveal a fundamental mechanism for maintaining nucleotide balance and position NUDT5 as a potential biomarker for predicting resistance to chemotherapy.

biochemistry↗

An updated inventory of genes essential for oxidative phosphorylation identifies a mitochondrial origin in familial Meniere disease

Mitochondrial disorders (MDs) are among the most common inborn errors of metabolism and primarily arise from defects in oxidative phosphorylation (OXPHOS). Their complex mode of inheritance and diverse clinical presentations render the diagnosis of MDs challenging and, to date, most lack a cure. Here, we build on previous efforts to discover genes necessary for OXPHOS and report a highly complementary galactose-sensitized CRISPR-Cas9 "growth" screen, presenting an updated inventory now with 481 OXPHOS genes, including 157 linked to MDs. We further focus on FAM136A, a gene associated with Menieres disease, and show that it supports inter-membrane space protein homeostasis and OXPHOS in cell lines, mice, and patients. Our study identifies a mitochondrial basis in a familial form of Menieres disease (fMD), provides a comprehensive resource of OXPHOS-related genes, and sheds light on the pathways involved in mitochondrial disorders, with the potential to guide future diagnostics and treatments for MDs. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/635272v1_ufig1.gif" ALT="Figure 1"> View larger version (79K): org.highwire.dtl.DTLVardef@1841a8forg.highwire.dtl.DTLVardef@1ebbaa8org.highwire.dtl.DTLVardef@12b70aeorg.highwire.dtl.DTLVardef@f2da2a_HPS_FORMAT_FIGEXP M_FIG C_FIG Bullet pointsO_LIGenome-wide CRISPR-Cas9 growth screening complements death screening C_LIO_LI481 genes essential for OXPHOS, including 157 mitochondrial disease genes C_LIO_LIFAM136A supports mitochondrial intermembrane space protein homeostasis C_LIO_LIDepletion of FAM136A in Menieres disease models causes OXPHOS defects C_LI

cell biology↗

Cytosolic N6AMT1-dependent translation supports mitochondrial RNA processing

Mitochondrial biogenesis relies on both the nuclear and mitochondrial genomes, and imbalance in their expression can lead to inborn error of metabolism, inflammation, and aging. Here, we investigate N6AMT1, a nucleo-cytosolic methyltransferase that exhibits genetic co-dependency with mitochondria. We determine transcriptional and translational profiles of N6AMT1 and report that it is required for the cytosolic translation of TRMT10C (MRPP1) and PRORP (MRPP3), two subunits of the mitochondrial RNAse P enzyme. In the absence of N6AMT1, or when its catalytic activity is abolished, RNA processing within mitochondria is impaired, leading to the accumulation of unprocessed and double-stranded RNA, thus preventing mitochondrial protein synthesis and oxidative phosphorylation. Our work sheds light on the function of N6AMT1 in protein synthesis and highlights a cytosolic program required for proper mitochondrial biogenesis.

molecular biology↗

From taxonomic to functional dark diversity: exploring the causes of potential biodiversity and its implications for conservation

O_LIDark diversity is an emerging and promising concept proposed to estimate the recruitment potential of natural communities and guide conservation and restoration policies. It represents all the species that could be present in a community due to favourable environmental conditions, but are currently lacking. To date, experimental approaches only measured taxonomic dark diversity, mainly based on species coexistence, which relies partly on neutral processes. Thus, these approaches may fail to identify the biodiversity which is lacking for deterministic reasons, and can hence hardly bring out suitable restoration methods. C_LIO_LIHere, we propose a novel method to estimate dark diversity, which is based on more deterministic coexistence: the coexistence of species functional features. We adapted the Beals co-occurrence index using functional groups, and we estimated functional dark diversity based on coexistence of functional groups. We then made use of functional dark diversity to address a persistent issue of restoration ecology: how does passive rewilding impact the ecological integrity of recovered communities? We compared spontaneous, secondary woodlands with ancient forests, in terms of taxonomic and functional dark diversity of vascular plants and spiders. C_LIO_LIOur results indicated that functional dark diversity does not equate to taxonomic dark diversity. Considering plants, recent woodlands surprisingly harboured less functional dark diversity than ancient forests, while they had a very similar amount of taxonomic dark diversity. Concerning spiders, recent woodlands harboured a similar amount of functional dark diversity as ancient forests, but more taxonomic dark diversity. Also, the composition of functional dark diversity differed between forest types, shedding light on their past assembly processes and unveiling their potential for conservation and effective restoration. C_LIO_LISynthesis and applications. Functional dark diversity brings novel perspectives for ecological diagnostic and restoration. Combined to taxonomic dark diversity, it enables to identify easily the deterministic constrains which limit the re-assembly of ecological communities after land-use changes and to predict the realistic, possible establishments of functional features. Here, we showed that spontaneous woodlands can have very similar, sometimes even higher, ecological integrity than that of ancient forests, and hence may be valuable habitats to be conserved from an ecological perspective. C_LI

ecology↗

Large herbivores strongly slow down litter decomposition in temperate forests

AO_SCPCAPBSTRACTC_SCPCAPIn temperate forest ecosystems, the role of deer in litter decomposition, a key nutrient cycling process, remains debated. Deer may modify the decomposition process by affecting plant cover and thus modifying litter abundance. They can also alter litter quality through differential browsing and affect decomposer ability by changing soil abiotic properties and the nature of decomposer communities. We used two litterbag experiments in a quasi-experimental situation resulting from the introduction of Sitka black-tailed deer Odocoileus odocoileus sitkensis on forested islands of Haida Gwaii (Canada). We investigated the effects of deer on decomposition through their impacts on litter quality and on decomposer ability. After one year, the effect of deer on litter quality resulted in a lower rate of mass loss in litter from litterbags. This mass loss mainly reflected a 21 and 38 % lower rate of carbon (C) and nitrogen (N) loss, respectively. Presence of deer resulted in lower decomposer ability for the rate of carbon loss, but not for nitrogen loss. The level of C loss after one year was 5% higher for litter decomposing on an island without deer. But the change in the rate of carbon loss explained by the effect of deer on decomposer ability was outweighed by the effect deer had on litter quality. Additional effects of deer on the decomposition process through feces deposition were significant but minor. These results question the role the large increase in deer populations observed in temperate forests at continental scales may play in broad scale patterns of C and N cycling.

ecology↗