Biology subjects

David, P.

Publications and source records attributed to David, P..

26 records · Page 2Linked to original sources

bioRxiv2020

MINPP1 prevents intracellular accumulation of the cation chelator inositol hexakisphosphate and is mutated in Pontocerebellar Hypoplasia

Inositol polyphosphates are vital metabolic and secondary messengers, involved in diverse cellular functions. Therefore, tight regulation of inositol polyphosphate metabolism is essential for proper cell physiology. Here, we describe an early-onset neurodegenerative syndrome caused by loss-of-function mutations in the multiple inositol polyphosphate phosphatase 1 gene (MINPP1). Patients were found to have a distinct type of Pontocerebellar Hypoplasia with typical basal ganglia involvement on neuroimaging. We found that patient-derived and genome edited MINPP1-/- induced pluripotent stem cells (iPSCs) are not able to differentiate efficiently into neurons. MINPP1 deficiency results in an intracellular imbalance of the inositol polyphosphate metabolism. This metabolic defect is characterized by an accumulation of highly phosphorylated inositols, mostly inositol hexakiphosphate (IP6), detected in HEK293, fibroblasts, iPSCs and differentiating neurons lacking MINPP1. In mutant cells, higher IP6 level is expected to be associated with an increased chelation of intracellular cations, such as iron or calcium, resulting in decreased levels of available ions. These data suggest the involvement of IP6-mediated chelation on Pontocerebellar Hypoplasia disease pathology and thereby highlight the critical role of MINPP1 in the regulation of human brain development and homeostasis.

genetics↗

bioRxiv2019

How community adaptation affects biodiversity-ecosystem-functioning relationships

Evidence is growing that evolutionary dynamics can impact biodiversity-ecosystem functioning (BEF) relationships. However the nature of such impacts remains poorly understood. Here we use a modelling approach to compare random communities, with no trait evolutionary fine-tuning, and co-adapted communities, where traits have co-evolved, in terms of emerging biodiversity-productivity, biodiversitystability, and biodiversity-invasion relationships. Community adaptation impacted most BEF relationships, sometimes inverting the slope of the relationship compared to random communities. Biodiversity-productivity relationships were generally less positive among co-adapted communities, with reduced contribution of sampling effects. The effect of community-adaptation, though modest regarding invasion resistance, was striking regarding invasion tolerance: co-adapted communities could remain very tolerant to invasions even at high diversity. BEF relationships are thus contingent on the history of ecosystems and their degree of community adaptation. Short-term experiments and observations following recent changes may not be safely extrapolated into the future, once eco-evolutionary feedbacks have taken place.

evolutionary biology↗

bioRxiv2019

Chromatin structure changes in Daphnia populations upon exposure to environmental cues - or - The discovery of Wolterecks \"Matrix\"

Phenotypic plasticity is an important feature of biological systems that is likely to play a major role in the future adaptation of organisms to the ongoing global changes. It may allow an organism to produce alternative phenotypes in responses to environmental cues. Modifications in the phenotype can be reversible but are sometimes enduring and can even span over generations. The notion of phenotypic plasticity was conceptualized in the early 20th century by Richard Woltereck. He introduced the idea that the combined relations of a phenotypic character and all environmental gradients that influence on it can be defined as \"norm of reaction\". Norms of reaction are specific to species and to lineages within species, and they are heritable. He postulated that reaction norms can progressively be shifted over generations depending on the environmental conditions. One of his biological models was the water-flee daphnia. Woltereck proposed that enduring phenotypic modifications and gene mutations could have similar adaptive effects, and he postulated that their molecular bases would be different. Mutations occurred in genes, while enduring modifications were based on something he called the Matrix. He suggested that this matrix (i) was associated with the chromosomes, (ii) that it was heritable, (iii) it changed during development of the organisms, and (iv) that changes of the matrix could be simple chemical substitutions of an unknown, but probably polymeric molecule. We reasoned that the chromatin has all postulated features of this matrix and revisited Wolterecks classical experiments with daphnia. We developed a robust and rapid ATAC-seq technique that allows for analyzing chromatin of individual daphnia and show here (i) that this technique can be used with minimal expertise in molecular biology, and (ii) we used it to identify open chromatin structure in daphnia exposed to different environmental cues. Our result indicates that chromatin structure changes consistently in daphnia upon this exposure confirming Wolterecks classical postulate.

evolutionary biology↗

bioRxiv2019

Looking for mimicry in a snake assemblage using deep learning

Batesian mimicry, with its highly colorful species and astonishing mimic-model resemblance, is a canonical example of evolution by natural selection. However, Batesian mimicry could also occur in inconspicuous species and rely on subtle resemblance. Although potentially widespread, such instances have been rarely investigated, such that the real frequency of Batesian mimicry has remained largely unknown. To fill this gap, we developed a new approach using deep learning to quantify the resemblance between putative mimics and models from photographs. We applied this method to quantify the frequency of Batesian mimicry in Western Palearctic snakes. Potential mimics were revealed by an excess of resemblance with sympatric venomous snakes compared to random expectations. We found that 8% of the non-venomous species were potential mimics, among which all were imperfect mimics. This study is the first to quantify the frequency of Batesian mimicry in a whole community of vertebrates, and shows that even concealed species can be reliably identified as potential models. Our approach should prove useful to detect mimicry in other communities, and more generally it highlights the benefits of deep learning for quantitative studies of phenotypic resemblance.

evolutionary biology↗

bioRxiv2019

Systematics and geographical distribution of Galba species, a group of cryptic and worldwide freshwater snails

Cryptic species can present a significant challenge to the application of systematic and biogeographic principles, especially if they are invasive or transmit parasites or pathogens. Detecting cryptic species requires a pluralistic approach in which molecular markers facilitate the detection of coherent taxonomic units that can then be analyzed using various traits (e.g., internal morphology) and crosses. In asexual or self-fertilizing species, the latter criteria are of limited use. We studied a group of cryptic freshwater snails (genus Galba) from the family Lymnaeidae that have invaded almost all continents, reproducing mainly by self-fertilization and transmitting liver flukes to humans and livestock. We aim to clarify the systematics, distribution and phylogenetic relationships of these species with an integrative approach that includes morphology (shell and reproductive anatomy), molecular markers, wide-scale sampling across America, and data retrieved from GenBank (to include Old World samples). Our phylogenetic analysis suggests that the genus Galba originated ca. 22 Myr ago and today comprises six clusters of species. Four of these clusters (G. truncatula, G. cubensis/viator, G. humilis and G. schirazensis) are morphologically cryptic and constitute species or species complexes with wide variation in their genetic diversity, geographic distribution and invasiveness. The other two clusters constitute a single species or a species complex (Galba cousini/meridensis) that demonstrate more geographically restricted distributions and exhibit an alternative morphology more phylogenetically derived than the cryptic one. Further genetic studies are required to clarify the status of both G. cousini/meridensis and G. cubensis/viator. We emphasize that no Galba species should be identified without molecular markers and that additional sampling is required, especially in North America, Eurasia and Africa to clarify remaining questions in systematics and biogeography. We also discuss several hypotheses that can explain crypsis in Galba, such as convergence and morphological stasis, and hypothesize a role for stabilizing selection in amphibious (rather than strictly freshwater) habitats.

evolutionary biology↗

bioRxiv2018

Assessing metacommunity processes through signatures in spatiotemporal turnover of community composition

Although metacommunity ecology has been a major field of research in the last decades, with both conceptual and empirical outputs, the analysis of the temporal dynamics of metacommunities has only emerged recently and consists mostly of repeated static analyses. Here, we propose a novel analytical framework to assess metacommunity processes using path analyses of spatial and temporal diversity turnovers. We detail the principles and practical aspects of this framework and apply it to simulated datasets to illustrate its ability to decipher the respective contributions of entangled drivers of metacommunity dynamics. We then apply it to four empirical datasets. Empirical results support the view that metacommunity dynamics may be generally shaped by multiple ecological processes acting in concert, with environmental filtering being variable across both space and time. These results reinforce our call to go beyond static analyses of metacommunities that are blind to the temporal part of environmental variability.

ecology↗

bioRxiv2018

A systems-level analysis highlights microglial activation as a modifying factor in common forms of human epilepsy

The common human epilepsies are associated with distinct patterns of reduced cortical thickness, detectable on neuroimaging, with important clinical consequences. To explore underlying mechanisms, we layered MRI-based cortical structural maps from a large-scale epilepsy neuroimaging study onto highly spatially-resolved human brain gene expression data, identifying >2,500 genes overexpressed in regions of reduced cortical thickness, compared to relatively-protected regions. The resulting set of differentially-expressed genes shows enrichment for microglial markers, and in particular, activated microglial states. Parallel analyses of cell-specific eQTLs show enrichment in human genetic signatures of epilepsy severity, but not epilepsy causation. Post mortem brain tissue from humans with epilepsy shows excess activated microglia. In an experimental model, depletion of activated microglia prevents cortical thinning, but not the development of chronic seizures. These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

neuroscience↗

bioRxiv2018

Sexual selection and inbreeding: two efficient ways to limit the accumulation of deleterious mutations

Theory and empirical data showed that two processes can boost selection against deleterious mutations, thus facilitating the purging of the mutation load: inbreeding, by exposing recessive deleterious alleles to selection in homozygous form, and sexual selection, by enhancing the relative reproductive success of males with small mutation loads. These processes tend to be mutually exclusive because sexual selection is reduced under mating systems that promote inbreeding, such as self-fertilization in hermaphrodites. We estimated the relative efficiency of inbreeding and sexual selection at purging the genetic load, using 50 generations of experimental evolution, in a hermaphroditic snail (Physa acuta). To this end, we generated lines that were exposed to various intensities of inbreeding, sexual selection (on the male function) and nonsexual selection (on the female function). We measured how these regimes affected the mutation load, quantified through the survival of outcrossed and selfed juveniles. We found that juvenile survival strongly decreased in outbred lines with reduced male selection, but not when female selection was relaxed, showing that male-specific sexual selection does purge deleterious mutations. However, in lines exposed to inbreeding, where sexual selection was also relaxed, survival did not decrease, and even increased for self-fertilized juveniles, showing that purging through inbreeding can compensate for the absence of sexual selection. Our results point to the further question of whether a mixed strategy combining the advantages of both mechanisms of genetic purging could be evolutionary stable.

evolutionary biology↗