Papers by Sandrine Hughes

Journal of Molecular Evolution, 2005
Based on morphological analyses, extant members of the order Crocodylia are divided into three fa... more Based on morphological analyses, extant members of the order Crocodylia are divided into three families, Alligatoridae, Crocodylidae, and Gavialidae. Gavialidae includes one species, the gharial, Gavialis gangeticus. In this study we have examined crocodilian relationships in phylogenetic analyses of seven mitochondrial genomes that have been sequenced in their entirety. The analyses did not support the morphologically acknowledged separate position of the gharial in the crocodilian tree. Instead the gharial joined the false gharial (Tomistoma schlegelii) on a common branch that was shown to constitute a sister group to traditional Crocodylidae (less Tomistoma). Thus, the analyses suggest the recognition of only two Crocodylia families, Alligatoridae and Crocodylidae, with the latter encompassing traditional Crocodylidae plus Gavialis/Tomistoma. A molecular dating of the divergence between Alligatoridae and Crocodylidae suggests that this basal split among recent crocodilians took place 140 million years before present, at the Jurassic/Cretaceous boundary. The results suggest that at least five crocodilian lineages survived the mass extinction at the KT boundary.
Journal of Molecular Evolution, 1997
The vertebrate genome underwent two major compositional transitions, between therapsids and mamma... more The vertebrate genome underwent two major compositional transitions, between therapsids and mammals and between dinosaurs and birds. These transitions concerned a sizable part (roughly one-third) of the genome, the gene-richest part of it, and consisted in an increase in GC levels (GC is the molar fraction of guanine + cytosine in DNA) which affected both coding sequences (especially third codon positions) and noncoding sequences. These major transitions were studied here by comparing GC 3 levels (GC 3 is the GC of third codon positions) of orthologous genes from Xenopus, chicken, calf, and man.

Transposable elements (TEs) are repeated DNA sequences potentially able to move throughout the ge... more Transposable elements (TEs) are repeated DNA sequences potentially able to move throughout the genome. In addition to their inherent mutagenic effects, TEs can disrupt nearby genes by donating their intrinsic regulatory sequences, for instance, promoting the ectopic expression of a cellular gene. TE transcription is therefore not only necessary for TE transposition per se but can also be associated with TE-gene fusion transcripts, and in some cases, be the product of pervasive transcription. Hence, correctly determining the transcription state of a TE copy is essential to apprehend the impact of the TE in the host genome. Methods to identify and quantify TE transcription have mostly relied on short RNAseq reads to estimate TE expression at the family level while using specific algorithms to discriminate copy-specific transcription. However, assigning short reads to their correct genomic location, and genomic feature is not trivial. Here we retrieved full-length cDNA (TeloPrime, Lexo...

During development, motor axons are guided towards their muscle target by various extrinsic cues ... more During development, motor axons are guided towards their muscle target by various extrinsic cues including extracellular matrix (ECM) proteins those identities remain poorly documented. Using single-cell RNA-sequencing of differentiating slow muscle progenitors (SMP) in zebrafish, we charaterized the SMP as a major source of ECM proteins that were computationally predicted to form a basement membrane-like structure tailored for motor axon guidance. Multiplein vivoandin vitroapproaches further revealed that motor axon shape and growth relies on the timely expression of the attractive cue Collagen XV-B (ColXV-B) that locally provides motor axons with a permissive soft microenvironment and separately organizes the repulsive cue Tenascin C into a unique functional dual topology. Bioprinted micropatterns mimicking their unique topology provide compelling evidence that it represents a sufficient condition to elicit directional motor axon growth. Our study provides the first evidence that ...

Insects living in nutritionally poor environments often establish long-term relationships with in... more Insects living in nutritionally poor environments often establish long-term relationships with intracellular bacteria that supplement their diets and improve their adaptive and invasive powers. Even though these symbiotic associations have been extensively studied on physiological, ecological and evolutionary levels, few studies have focused on the molecular dialogue between host and endosymbionts to identify genes and pathways involved in endosymbiosis control and dynamics. We simultaneously analyzed host and endosymbiont gene expression during the life cycle of the cereal weevilSitophilus oryzae, from larval stages to adults, with a particular emphasis on emerging adults where the endosymbiontSodalis pierantoniusexperiences a contrasted growth-climax-elimination dynamics. We unraveled a constant arms race in which different biological functions are intertwined and coregulated across both partners. These include immunity, metabolism, metal control, apoptosis, and bacterial stress r...

Biological pathways rely on the formation of intricate protein interaction networks called intera... more Biological pathways rely on the formation of intricate protein interaction networks called interactomes. Getting a comprehensive map of interactomes implies developing tools that allow capturing transient and low affinity protein-protein interactions (PPIs) in live conditions. Here we present an experimental strategy, Cell-PCA (Cell Protein Complementation Assay), which is based on BiFC (Bimolecular Fluorescence Complementation) and high throughput sequencing for ORFeome-wide analyses of different interactomes in the same live cell context. The specificity and sensitivity of Cell-PCA was established by using a wild type and a single amino-acid mutated HOXA9 protein, and the approach was subsequently applied for seven additional human HOX proteins. These proof-of-concept experiments revealed novel molecular properties of HOX interactomes and led to the identification of a novel cofactor of HOXB13 for promoting its proliferative activity in a cancer cell context. Taken together, our w...
Journal of Investigative Dermatology
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific r... more HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
HAL (Le Centre pour la Communication Scientifique Directe), Apr 29, 2022

BackgroundMany insects house symbiotic intracellular bacteria (endosymbionts) that provide them w... more BackgroundMany insects house symbiotic intracellular bacteria (endosymbionts) that provide them with essential nutrients, thus promoting usage of nutrient-poor habitats. Endosymbiont seclusion within host specialized cells, called bacteriocytes, often organized in a dedicated organ, the bacteriome, is crucial in protecting them from host immune defenses while avoiding chronic host immune activation. Previous evidence obtained in the cereal weevil Sitophilus oryzae has shown that bacteriome immunity is activated against invading pathogens, suggesting endosymbionts might be targeted and impacted by immune effectors during an immune challenge. To pinpoint any molecular determinants associated with such challenges, we conducted a dual transcriptomic analysis of S. oryzae’s bacteriome subjected to immunogenic peptidoglycan fragments.ResultsWe show that upon immune challenge the bacteriome actively participates in the innate immune response via an induction of antimicrobial peptides (AMPs...

ABSTRACTRegenerating animals have the ability to reproduce organs that were originally generated ... more ABSTRACTRegenerating animals have the ability to reproduce organs that were originally generated in the embryo and subsequently lost due to injury. Understanding whether the process of regeneration mirrors development is an open question in most regenerative species. Here we take a transcriptomics approach to examine to what extent leg regeneration shows the same temporal patterns of gene expression as leg development in the embryo, in the crustacean Parhyale hawaiensis. We find that leg development in the embryo shows stereotypic temporal patterns of gene expression. In contrast, global patterns of gene expression during leg regeneration show a high degree of variation, related to the physiology of individual animals. A major driver of this variation is the molting cycle. After dissecting the transcriptional signals of individual physiology from regeneration, we obtain temporal signals that mark distinct phases of leg regeneration. Comparing the transcriptional dynamics of developm...

Symbiotic bacteria interact with their host through symbiotic cues. Here, we took advantage of th... more Symbiotic bacteria interact with their host through symbiotic cues. Here, we took advantage of the mutualism between Drosophila andLactiplantibacillus plantarum(Lp) to investigate a novel mechanism of host-symbiont interaction. Using chemically-defined diets, we found that association with Lp improves the growth of larvae fed amino acid-imbalanced diets, even though Lp cannot produce the limiting amino acid. We show that in this context Lp supports its host’s growth through a molecular dialog that requires functional operons encoding ribosomal and transfer RNAs (r/tRNAs) in Lp and the GCN2 kinase in Drosophila’s enterocytes. Our data indicate Lp’s r/tRNAs are packaged in extracellular vesicles and activate GCN2 in a subset of larval enterocytes, a mechanism necessary to remodel the intestinal transcriptome and ultimately to support anabolic growth. Based on our findings, we propose a novel beneficial molecular dialog between host and microbes, which relies on a non-canonical role of...

Proceedings of the National Academy of Sciences, 2020
SignificanceVirtually all animals are associated with symbiotic bacteria. How these associations ... more SignificanceVirtually all animals are associated with symbiotic bacteria. How these associations are modulated across an animal’s life cycle is a key question in understanding animal–bacteria interactions, particularly in organisms that undergo metamorphosis during development. Here, we used the cereal weevil to show how symbiosis is reorganized during metamorphosis, a developmental process entailing drastic tissue rearrangements. In this insect, symbionts are housed within specialized host cells, the bacteriocytes, that form the bacteriome tissue. We show that the bacteriome is completely remodeled during metamorphosis through host–symbiont communication, involving adhesion and motility host proteins and a temporary symbiont infectious behavior. This interkingdom dialogue results in the adaptation of the bacteriome to adulthood, highlighting the intertwining of symbiosis with host development.
Animal-microbe facultative symbioses play a fundamental role in ecosystem and organismal health (... more Animal-microbe facultative symbioses play a fundamental role in ecosystem and organismal health (1–3). Yet, due to the flexible nature of their association, the selection pressures acting on animals and their facultative symbionts remain elusive (4, 5). Here, by applying experimental evolution to a well-established model of facultative symbiosis: Drosophila melanogaster associated with Lactobacillus plantarum, one of its growth promoting symbiont (6, 7), we show that the diet, instead of the host, is a predominant driving force in the evolution of this symbiosis and identify the mechanism resulting from the bacterial adaptation to the diet, which confers host growth benefits. Our study reveals that adaptation to the diet can be the foremost step in the determination of the evolutionary course of a facultative symbiosis.

Cell host & microbe, Jan 11, 2018
Animal-microbe facultative symbioses play a fundamental role in ecosystem and organismal health. ... more Animal-microbe facultative symbioses play a fundamental role in ecosystem and organismal health. Yet, due to the flexible nature of their association, the selection pressures that act on animals and their facultative symbionts remain elusive. Here we apply experimental evolution to Drosophila melanogaster associated with its growth-promoting symbiont Lactobacillus plantarum, representing a well-established model of facultative symbiosis. We find that the diet of the host, rather than the host itself, is a predominant driving force in the evolution of this symbiosis. Furthermore, we identify a mechanism resulting from the bacterium's adaptation to the diet, which confers growth benefits to the colonized host. Our study reveals that bacterial adaptation to the host's diet may be the foremost step in determining the evolutionary course of a facultative animal-microbe symbiosis.

eLife, Oct 30, 2017
Larval recruitment, the transition of pelagic larvae into reef-associated juveniles, is a critica... more Larval recruitment, the transition of pelagic larvae into reef-associated juveniles, is a critical step for the resilience of marine fish populations but its molecular control is unknown. Here, we investigate whether thyroid-hormones (TH) and their receptors (TR) coordinate the larval recruitment of the coral-reef-fish . We demonstrate an increase of TH-levels and -expressions in pelagic-larvae, followed by a decrease in recruiting juveniles. We generalize these observations in four other coral reef-fish species. Treatments with TH or TR-antagonist, as well as relocation to the open-ocean, disturb larvae transformation and grazing activity. Likewise, chlorpyrifos, a pesticide often encountered in coral-reefs, impairs TH-levels, transformation, and grazing activity, hence diminishing this herbivore's ability to control the spread of reef-algae. Larval recruitment therefore corresponds to a TH-controlled metamorphosis, sensitive to endocrine disruption. This provides a framework t...

SummaryThe microbial environment influence animal physiology. However, the underlying molecular m... more SummaryThe microbial environment influence animal physiology. However, the underlying molecular mechanisms of such functional interactions are largely undefined. Previously, we showed that upon chronic undernutrition, strains of Lactobacillus plantarum, a dominant commensal partner of Drosophila, promote host juvenile growth and maturation partly via enhanced expression of intestinal peptidases. By screening a transposon insertion library of Lactobacillus plantarum in gnotobiotic Drosophila larvae, we identify a bacterial cell wall modifying machinery encoded by the pbpX2-dltXABCD operon that is critical to enhance host digestive capabilities and promote growth and maturation. Deletion of this operon leads to bacterial cell wall alteration with a complete loss of teichoic acids D-alanylation. We thus conclude that teichoic acids modifications participate in commensal-host interactions and specifically, D-alanine esterification of teichoic acids contributes to optimal L. plantarum me...

Genome Biology and Evolution, 2017
Parasites are sometimes able to manipulate the behavior of their hosts. However, the molecular cu... more Parasites are sometimes able to manipulate the behavior of their hosts. However, the molecular cues underlying this phenomenon are poorly documented. We previously reported that the parasitoid wasp Leptopilina boulardi which develops from Drosophila larvae is often infected by an inherited DNA virus. In addition to being maternally transmitted, the virus benefits from horizontal transmission in superparasitized larvae (Drosophila that have been parasitized several times). Interestingly, the virus forces infected females to lay eggs in already parasitized larvae, thus increasing the chance of being horizontally transmitted. In a first step towards the identification of virus genes responsible for the behavioral manipulation, we present here the genome sequence of the virus, called LbFV. The sequencing revealed that its genome contains an homologous repeat sequence (hrs) found in eight regions in the genome. The presence of this hrs may explain the genomic plasticity that we observed ...

Journal of Biological Chemistry, 2016
Thyroid hormones modulate not only multiple functions in vertebrates (energy metabolism, central ... more Thyroid hormones modulate not only multiple functions in vertebrates (energy metabolism, central nervous system function, seasonal changes in physiology, and behavior) but also in some non-vertebrates where they control critical post-embryonic developmental transitions such as metamorphosis. Despite their obvious biological importance, the thyroid hormone precursor protein, thyroglobulin (Tg), has been experimentally investigated only in mammals. This may bias our view of how thyroid hormones are produced in other organisms. In this study we searched genomic databases and found Tg orthologs in all vertebrates including the sea lamprey (Petromyzon marinus). We cloned a full-size Tg coding sequence from western clawed frog (Xenopus tropicalis) and zebrafish (Danio rerio). Comparisons between the representative mammal, amphibian, teleost fish, and basal vertebrate indicate that all of the different domains of Tg, as well as Tg regional structure, are conserved throughout the vertebrates. Indeed, in Xenopus, zebrafish, and lamprey Tgs, key residues, including the hormonogenic tyrosines and the disulfide bond-forming cysteines critical for Tg function, are well conserved despite overall divergence of amino acid sequences. We uncovered upstream sequences that include start codons of zebrafish and Xenopus Tgs and experimentally proved that these are full-length secreted proteins, which are specifically recognized by antibodies against rat Tg. By contrast, we have not been able to find any orthologs of Tg among non-vertebrate species. Thus, Tg appears to be a novel protein elaborated as a single event at the base of vertebrates and virtually unchanged thereafter.

The ability of many bacteria to adapt to diverse environmental conditions is well known. Recent r... more The ability of many bacteria to adapt to diverse environmental conditions is well known. Recent research has linked the process of bacterial adaptation to a niche to changes in the genome content and size, showing that many bacterial genomes reflect the constraints imposed by their habitat. However, some highly versatile bacteria are found in diverse niches that almost share nothing in common. Lactobacillus plantarum is a lactic acid bacterium that is found in a large variety of niches. With the aim of unravelling the link between genome evolution and ecological versatility of L. plantarum, we analysed the genomes of 54 L. plantarum strains isolated from different environments. Phylogenomic analyses coupled with the study of genetic functional divergence and gene-trait matching analysis revealed a mixed distribution of the strains, which was uncoupled from their environmental origin. Our findings demonstrate the high complexity of L. plantarum evolution, revealing the absence of spe...
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Papers by Sandrine Hughes