Biology subjects

Chantepie, S.

Publications and source records attributed to Chantepie, S..

4 recordsLinked to original sources

bioRxiv2024

Evolution of genetic (co)variances during the worldwide invasion of Drosophila suzukii

The extent to which phenotypic evolution can be constrained by genetic correlations is an important question in evolutionary biology. To address this question, biological invasions are opportune models where derived, invasive populations can be compared to their extant ancestors, allowing to track the evolution of genetic correlations from the ancestor, throughout the invasion process. In this paper, we focused on the worldwide invasion of Drosophila suzukii (Matsumara, 1931), and investigated the evolution of the genetic covariance matrix G of wing shape between ancestral native, and derived invasive populations. Leveraging demographic history resolved by population genetics approaches, we tested whether G remained stable during the invasion. Using a multivariate QST-FST approach, we further tested whether or not the observed phenotypic divergence in wing shape aligned with a neutral scenario of evolution. Our results show moderate yet significant quantitative genetic differentiation of wing shape among D. suzukii populations and a relative stability in the structure of G, presenting a roughly spherical shape but slightly different volumes. These characteristics likely reflect the demographic history of populations and suggest a low level of genetic constraint on wing shape evolution. The divergence between populations was greater than expected under a purely neutral model of evolution, compatible with an effect of divergent selection among them. Overall, our study suggests that selection and drift, but not ancestral genetic constraints, affected the early stages of wing shape evolution during D. suzukii invasion.

evolutionary biology↗

bioRxiv2022

Reproducing extracellular matrix adverse remodelling of non-ST myocardialinfarction in a large animal model

The rising incidence of non-ST-segment elevation myocardial infarction (NSTEMI) and associated long-term high mortality constitutes an urgent clinical issue. Unfortunately, the study of possible interventions to treat this pathology lacks a reproducible pre-clinical model. Indeed, currently adopted small and large animal models of MI mimic only full-thickness, ST-segment-elevation (STEMI) infarcts, and hence cater only for investigation into therapeutics and interventions directed at this subset of MI. Thus, we developed an ovine model of NSTEMI by ligating the myocardial muscle at precise intervals parallel to the left anterior descending coronary artery. After validating the presented model both by histology and functional analysis with clinical data, further omics analyses highlighted the distinctive features of post-NSTEMI tissue remodelling. Here, by looking at the transcriptome and proteome-derived pathways emerging at acute (7 days) and late (28 days) post-surgery timepoints, we discovered specific alterations in cardiac post-ischaemic extracellular matrix (ECM). Together with the rise of well-known markers of inflammation and fibrosis, NSTEMI ischaemic regions showed distinctive patterns in the expression of complex N-glycans and glycosaminoglycans in cellular membranes and ECM. Identifying such changes in molecular moieties accessible to infusible and intra-myocardial injectable drugs sheds light on the development of targeted pharmacological solutions to contrast adverse fibrotic remodelling.

bioengineering↗

bioRxiv2020

How does the strength of selection influence genetic correlations ?

Genetic correlations between traits can strongly impact evolutionary responses to selection, and may thus impose constraints on adaptation. Theoretical and empirical work has made it clear that, without strong linkage, genetic correlations at evolutionary equilibrium result from an interplay of correlated pleiotropic effects of mutations, and correlational selection favoring combinations of trait values. However, it is not entirely clear how the strength of stabilizing selection influences this compromise between mutation and selection effects on genetic correlations. Here, we show that the answer to this question crucially depends on the intensity of genetic drift. In large, effectively infinite populations, genetic correlations are unaffected by the strength of selection, regardless of whether the genetic architecture involves common small-effect mutations (Gaussian regime), or rare large-effect mutations (House-of-Cards regime). In contrast in finite populations, the strength of selection does affect genetic correlations, by shifting the balance from drift-dominated to selection-dominated evolutionary dynamics. The transition between these domains depends on mutation parameters to some extent, but with a similar dependence of genetic correlation on the strength of selection. Our results are particularly relevant for understanding how senescence shapes patterns of genetic correlations across ages, and genetic constraints on adaptation during colonization of novel habitats.

evolutionary biology↗

bioRxiv2018

New tools for carbohydrate sulphation analysis: Heparan Sulphate 2-O-sulphotranserase (HS2ST) is a target for small molecule protein kinase inhibitors

Sulphation of carbohydrate residues occurs on a variety of glycans destined for secretion, and this modification is essential for efficient matrix-based signal transduction. Heparan sulphate (HS) glycosaminoglycans control physiological functions ranging from blood coagulation to cell proliferation. HS biosynthesis involves membrane-bound Golgi sulphotransferases, including heparan sulphate 2-O-sulphotransferase (HS2ST), which transfers sulphate from the co-factor PAPS (3-phosphoadenosine 5-phosphosulphate) to the 2-O position of -L-iduronate in the maturing oligosaccharide chain. The current lack of simple non-radioactive enzyme assays that can be used to quantify the levels of carbohydrate sulphation hampers kinetic analysis of this process and the discovery of HS2ST inhibitors. In this paper, we describe a new procedure for thermal shift analysis of purified HS2ST. Using this approach, we quantify HS2ST-catalyzed oligosaccharide sulphation using a novel synthetic fluorescent substrate and screen the Published Kinase Inhibitor Set (PKIS), to evaluate compounds that inhibit catalysis. We report the susceptibility of HS2ST to a variety of cell permeable compounds in vitro, including polyanionic polar molecules, the protein kinase inhibitor rottlerin and oxindole-based RAF kinase inhibitors. In a related study, published back-to-back with this article, we demonstrate that Tyrosyl Protein Sulpho Tranferases (TPSTs) are also inhibited by a variety of protein kinase inhibitors. We propose that appropriately validated small molecule compounds could become new tools for rapid inhibition of glycan (and protein) sulphation in cells, and that protein kinase inhibitors might be repurposed or redesigned for the specific inhibition of HS2ST.\n\nSUMMARY STATEMENTWe report that HS2ST, which is a PAPS-dependent glycan sulphotransferase, can be assayed using a variety of novel biochemical procedures, including a non-radioactive enzyme-based assay that detects glycan substrate sulphation in real time. HS2ST activity can be inhibited by different classes of compounds, including known protein kinase inhibitors, suggesting new approaches to evaluate the roles of HS2ST-dependent sulphation with small molecules in cells.

biochemistry↗