Biology subjects

Gauthier, K.

Publications and source records attributed to Gauthier, K..

6 recordsLinked to original sources

bioRxiv2024

Population genomics and molecular epidemiology of wheat powdery mildew in Europe

Agricultural diseases are a major threat to sustainable food production. Yet, for many pathogens we know exceptionally little about their epidemiological and population dynamics, and this knowledge gap is slowing the development of efficient control strategies. Here we study the population genomics and molecular epidemiology of wheat powdery mildew, a disease caused by the biotrophic fungus Blumeria graminis forma specialis tritici (Bgt). We sampled Bgt for two consecutive years, 2022 and 2023, from 22 countries in Europe and surrounding regions, and compiled a genomic dataset of 415 Bgt isolates. We found one single epidemic unit in the north of Europe, consisting of a highly homogeneous population. Conversely, the south of Europe hosts smaller local populations which are less interconnected. In addition, we show that the population structure can be largely predicted by the prevalent wind patterns. We identified several loci that were under selection in the recent past, including fungicide targets and avirulence genes. Some of these loci are common between populations, while others are not, suggesting different local selective pressures. We reconstructed the evolutionary history of one of these loci, AvrPm17, coding for an effector recognized by the wheat receptor Pm17. We found evidence for a soft sweep on standing genetic variation. Multiple AvrPm17 haplotypes, which can partially escape recognition by Pm17, spread rapidly throughout the continent upon its introduction in the early 2000s. We also identified a new virulent variant, which emerged more recently and can evade Pm17 resistance altogether. Overall, we highlight the potential of genomic surveillance in resolving the evolutionary and epidemiological dynamics of agricultural pathogens, as well as in guiding control strategies.

evolutionary biology↗

bioRxiv2024

k-mer-based GWAS in a wheat collection reveals novel and diverse sources of powdery mildew resistance

BackgroundWheat landraces and cultivars stored in gene banks worldwide represent a valuable source of genetic diversity for discovering genes critical for agriculture, which is increasingly constrained by climate change and inputs reduction. We assembled and genotyped, using DArTseq technology, a panel of 461 accessions representative of the genetic diversity of Swiss wheat material. The collection was evaluated for powdery mildew resistance under field conditions for two consecutive years and at the seedling stage with 10 different wheat powdery mildew isolates. ResultsTo identify the genetic basis of mildew resistance in wheat, we developed a k-mer-based GWAS approach using multiple fully-assembled genomes including Triticum aestivum as well as four progenitor genomes. Compared to approaches based on single reference genomes, we unambiguously mapped an additional 25% resistance-associated k-mers. Our approach outperformed SNP-based GWAS in terms of number of loci identified and precision of mapping. In total, we detected 34 (Pm) powdery mildew resistance loci, including seven previously-described and more importantly 27 novel loci active at the seedling stage. Furthermore, we identified a region associated with adult plant resistance, which was not detected with SNP-based approaches. ConclusionsThe described non-reference-based approach highlights the potential of integrating multiple wheat reference genomes with k-mer GWAS to harness the untapped genetic diversity present in germplasm collections.

genomics↗

bioRxiv2024

Estrogen receptor-related receptor (Esrra) induces ribosomal protein Rplp1-mediated adaptive hepatic translation during prolonged starvation

Protein translation is an energy-intensive ribosome-driven process that is reduced during nutrient scarcity to conserve cellular resources. During prolonged starvation, cells selectively translate specific proteins to enhance their survival (adaptive translation); however, this process is poorly understood. Accordingly, we analyzed protein translation and mRNA transcription by multiple methods in vitro and in vivo to investigate adaptive hepatic translation during starvation. While acute starvation suppressed protein translation in general, proteomic analysis showed that prolonged starvation selectively induced translation of lysosome and autolysosome proteins. Significantly, the expression of the orphan nuclear receptor, estrogen-related receptor alpha (Esrra) increased during prolonged starvation and served as a master regulator of this adaptive translation by transcriptionally stimulating 60S acidic ribosomal protein P1 (Rplp1) gene expression. Overexpression or siRNA knockdown of Esrra expression in vitro or in vivo led to parallel changes in Rplp1 gene expression, lysosome/autophagy protein translation, and autophagy. Remarkably, we have found that Esrra had dual functions by not only regulating transcription but also controling adaptive translation via the Esrra/Rplp1/lysosome/autophagy pathway during prolonged starvation.

molecular biology↗

bioRxiv2022

Brown adipocytes local response to thyroid hormone is required for adaptive thermogenesis in adult male mice

Thyroid hormone (T3) and its nuclear receptors (TR) are important regulators of energy expenditure and adaptive thermogenesis, notably through their action in the brown adipose tissue (BAT). However, T3 acts in many other peripheral and central tissues which are also involved in energy expenditure. The general picture of how T3 regulates BAT thermogenesis is currently not fully established, notably due to the absence of extensive omics analyses and the lack of specific mice model. Here, we first used transcriptome and cistrome analyses to establish the list of T3/TR direct target genes in brown adipocytes. We then developed a novel model of transgenic mice, in which T3-signaling is specifically suppressed in brown adipocytes at adult stage. We addressed the capacity of these mice to mount a thermogenic response when challenged by either a cold exposure or a high-fat diet, and analyzed the associated changes in BAT transcriptome. We conclude that T3 plays a crucial role in the thermogenic response of the BAT, controlling the expression of genes involved in lipid and glucose metabolism and regulating BAT proliferation. The resulting picture provides an unprecedented view on the pathways by which T3 activates energy expenditure through an efficient adaptive thermogenesis in the BAT. Significance StatementThyroid hormones (TH) increase energy expenditure by regulating the expression of target genes in many metabolic tissues. Among them, brown adipose tissue (BAT) dissipates biochemical energy into heat production to notably prevent hypothermia during cold exposure. Hypothyroid mice display inefficient BAT thermogenesis suggesting that TH are crucial for this process. Here, we eliminated TH signaling specifically in brown adipocytes and expose the mice to different physiological stressors. We showed that TH signaling is crucial for BAT thermogenesis as it controls the expression of genes involved in proliferation and in the metabolism of lipids and glucose, the main energy resources for BAT thermogenesis. This study provides an unprecedented view on the pathways by which T3 activates energy expenditure the BAT.

genomics↗

bioRxiv2022

The multi-level regulation of clownfish metamorphosis by thyroid hormones

Most marine organisms have a biphasic life cycle during which a pelagic larva is transformed into a radically different juvenile. In vertebrates the role of thyroid hormones (TH) in triggering this transition is well known, but how the morphological and physiological changes are integrated in a coherent way with the ecological transition remains poorly explored. To gain insight into this question, we performed an integrative analysis of metamorphosis of a marine teleost, the clownfish Amphiprion ocellaris. We reveal how TH coordinate a change in color vision as well as a major metabolic shift in energy production, hence highlighting its central integrative role in regulating this transformation. By manipulating the activity of LXR, a major regulator of metabolism, we also reveal a tight link between metabolic changes and metamorphosis progression. Strikingly, we observed that these regulations are at play in the wild revealing how hormones coordinate energy needs with available resources during life cycle.

developmental biology↗

bioRxiv2021

Estrogen-related receptor alpha and Rplp1 ribosome protein-dependent translation coordinately regulate starvation response and decrease NASH progression

BackgroundCurrently, little is known about the mechanism(s) regulating global and specific protein translation during non-alcoholic steatohepatitis (NASH). MethodsWe used puromycin-labelling, polysome profiling, ChIPseq and ChIP-qPCR, and gene manipulation in vitro and in dietary mouse models of NASH in this study. ResultsUsing unbiased label-free quantitative proteome, puromycin-labelling and polysome profiling, we observed a global decrease in protein translation during lipotoxicity in human primary hepatocytes, mouse hepatic AML12 cells, and livers from a dietary mouse model of NASH. Interestingly, proteomic analysis showed that Rplp1, which regulates ribosome and translation pathways, was one of the most downregulated proteins. Moreover, decreased Esrra expression and binding to the Rplp1 promoter, diminished Rplp1 gene expression during lipotoxicity. This, in turn, reduced global protein translation and Esrra/Rplp1-dependent translation of lysosome (Lamp2, Ctsd) and autophagy (sqstm1, Map1lc3b) proteins. Of note, Esrra did not increase its binding to these gene promoters or their gene transcription, confirming its regulation of their translation during lipotoxicity. Notably, hepatic Esrra-Rplp1-dependent translation of lysosomal and autophagy proteins also was impaired in NASH patients and liver-specific Esrra knockout mice. Remarkably, alternate day fasting induced Essra-Rplp1-dependent expression of lysosomal proteins, restored autophagy, and reduced lipotoxicity, inflammation, and fibrosis in hepatic cell culture and in vivo models of NASH. ConclusionEsrra regulation of Rplp1-mediated translation of lysosome / autolysosome proteins was downregulated during NASH. Alternate day fasting activated this novel pathway and improved NASH, suggesting that Esrra and Rplp1 may serve as therapeutic targets for NASH. Our findings also provided the first example of a nuclear hormone receptor, Esrra, to not only regulate transcription but also protein translation, via induction of Rplp1.

molecular biology↗