Partial Amniote Sex Chromosomal Linkage Homologies Shared on Snake W Sex Chromosomes Support the Ancestral Super-Sex Chromosome Evolution in Amniotes

Squamate reptile chromosome 2 (SR2) is thought to be an important remnant of an ancestral amniote super-sex chromosome, but a recent study showed that the Siamese cobra W sex chromosome is also a part of this larger ancestral chromosome. To confirm the existence of an ancestral amniote super-sex chromosome and understand the mechanisms of amniote sex chromosome evolution, chromosome maps of two snake species [Russell’s viper: Daboia russelii (DRU) and the common tiger snake: Notechis scutatus (NSC)] were constructed using bacterial artificial chromosomes (BACs) derived from chicken and zebra finch libraries containing amniote sex chromosomal linkages. Sixteen BACs were mapped on the W sex chromosome of DRU and/or NSC, suggesting that these BACs contained a common genomic region shared with the W sex chromosome of these snakes. Two of the sixteen BACs were co-localized to DRU2 and NSC2, corresponding to SR2. Prediction of genomic content from all BACs mapped on snake W sex chromosomes revealed a large proportion of long interspersed nuclear element (LINE) and short interspersed nuclear element (SINE) retrotransposons. These results led us to predict that amplification of LINE and SINE may have occurred on snake W chromosomes during evolution. Genome compartmentalization, such as transposon amplification, might be the key factor influencing chromosome structure and differentiation. Multiple sequence alignments of all BACs mapped on snake W sex chromosomes did not reveal common sequences. Our findings indicate that the SR2 and snake W sex chromosomes may have been part of a larger ancestral amniote super-sex chromosome, and support the view of sex chromosome evolution as a colorful myriad of situations and trajectories in which many diverse processes are in action

Endothelin-Dependent Vasoconstriction in Human Uterine Artery: Application to Preeclampsia

BACKGROUND: Reduced uteroplacental perfusion, the initiating event in preeclampsia, is associated with enhanced endothelin-1 (ET-1) production which feeds the vasoconstriction of uterine artery. Whether the treatments of preeclampsia were effective on ET-1 induced contraction and could reverse placental ischemia is the question addressed in this study. We investigated the effect of antihypertensive drugs used in preeclampsia and of ET receptor antagonists on the contractile response to ET-1 on human uterine arteries. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed, ex vivo, on human uterine artery samples obtained after hysterectomy. We studied variations in isometric tension of arterial rings in response to the vasoconstrictor ET-1 and evaluated the effects of various vasodilators and ET-receptor antagonists on this response. Among antihypertensive drugs, only dihydropyridines were effective in blocking and reversing the ET-1 contractile response. Their efficiency, independent of the concentration of ET-1, was only partial. Hydralazine, alpha-methyldopa and labetalol had no effect on ET-1 induced contraction which is mediated by both ET(A) and ET(B) receptors in uterine artery. ET receptors antagonists, BQ-123 and BQ-788, slightly reduced the amplitude of the response to ET-1. Combination of both antagonists was more efficient, but it was not possible to reverse the maximal ET-1-induced contraction with antagonists used alone or in combination. CONCLUSION: Pharmacological drugs currently used in the context of preeclampsia, do not reverse ET-1 induced contraction. Only dihydropyridines, which partially relax uterine artery previously contracted with ET-1, might offer interesting perspectives to improve placental perfusion

Improved reference genome uncovers novel sex-linked regions in the Guppy (Poecilia reticulata)

This is the author accepted manuscript. The final version is available on open access from Oxford University Press via the DOI in this recordData availability: Population genomics data are available on ENA: Study: PRJEB10680 PCR-free data are available on ENA: Study PRJEB36450 Genome assembly is available on ENA ID: PRJEB36704; ERP119926 All scripts and pipelines are available on github: https://github.com/bfrasercommits/guppy_genomeTheory predicts that the sexes can achieve greater fitness if loci with sexually antagonistic polymorphisms become linked to the sex determining loci, and this can favour the spread of reduced recombination around sex determining regions. Given that sex-linked regions are frequently repetitive and highly heterozygous, few complete Y chromosome assemblies are available to test these ideas. The guppy system (Poecilia reticulata) has long been invoked as an example of sex chromosome formation resulting from sexual conflict. Early genetics studies revealed that male colour patterning genes are mostly but not entirely Y-linked, and that X-linkage may be most common in low predation populations. More recent population genomic studies of guppies have reached varying conclusions about the size and placement of the Y-linked region. However, this previous work used a reference genome assembled from short-read sequences from a female guppy. Here, we present a new guppy reference genome assembly from a male, using long-read PacBio single-molecule real-time sequencing (SMRT) and chromosome contact information. Our new assembly sequences across repeat- and GC-rich regions and thus closes gaps and corrects mis-assemblies found in the short-read female-derived guppy genome. Using this improved reference genome, we then employed broad population sampling to detect sex differences across the genome. We identified two small regions that showed consistent male-specific signals. Moreover, our results help reconcile the contradictory conclusions put forth by past population genomic studies of the guppy sex chromosome. Our results are consistent with a small Y-specific region and rare recombination in male guppies.Max Planck SocietyEuropean Research Council (ERC)Natural Environment Research Council (NERC

Transcriptome Analysis during Human Trophectoderm Specification Suggests New Roles of Metabolic and Epigenetic Genes

In humans, successful pregnancy depends on a cascade of dynamic events during early embryonic development. Unfortunately, molecular data on these critical events is scarce. To improve our understanding of the molecular mechanisms that govern the specification/development of the trophoblast cell lineage, the transcriptome of human trophectoderm (TE) cells from day 5 blastocysts was compared to that of single day 3 embryos from our in vitro fertilization program by using Human Genome U133 Plus 2.0 microarrays. Some of the microarray data were validated by quantitative RT-PCR. The TE molecular signature included 2,196 transcripts, among which were genes already known to be TE-specific (GATA2, GATA3 and GCM1) but also genes involved in trophoblast invasion (MUC15), chromatin remodeling (specifically the DNA methyltransferase DNMT3L) and steroid metabolism (HSD3B1, HSD17B1 and FDX1). In day 3 human embryos 1,714 transcripts were specifically up-regulated. Besides stemness genes such as NANOG and DPPA2, this signature included genes belonging to the NLR family (NALP4, 5, 9, 11 and 13), Ret finger protein-like family (RFPL1, 2 and 3), Melanoma Antigen family (MAGEA1, 2, 3, 5, 6 and 12) and previously unreported transcripts, such as MBD3L2 and ZSCAN4. This study provides a comprehensive outlook of the genes that are expressed during the initial embryo-trophectoderm transition in humans. Further understanding of the biological functions of the key genes involved in steroidogenesis and epigenetic regulation of transcription that are up-regulated in TE cells may clarify their contribution to TE specification and might also provide new biomarkers for the selection of viable and competent blastocysts

Impact of transposable elements on the evolution of gene expression : example of sex in teleost fish

Chez les poissons téléostéens, les modes de reproduction sexuée et les réseaux de régulation des gènes liés au sexe sont très variables. La détermination du sexe des espèces gonochoriques, par exemple, peut être aussi bien génétique qu'environnementale et peut impliquer des gènes différents selon les espèces. Les régulations du développement et du maintien du sexe apparaissent également variables dans ce groupe. Pour essayer de comprendre l'origine de cette diversité, je me suis intéressé à l'impact possible des éléments transposables sur la régulation de gènes liés au sexe chez ces poissons. Bien que souvent neutres, et parfois délétères pour leur hôte, les éléments transposables peuvent aussi transporter des séquences régulatrices, comme des sites de fixation de facteurs de transcription, et les disséminer à travers les génomes. Pour tester cette hypothèse, j'ai utilisé des données de séquençage d'ARN issues de gonades mâles et femelles d'Oryzias latipes, le médaka japonais. Dans un premier temps, j'ai analysé l'expression des gènes et des éléments transposables et mis en évidence des régions du génome enrichies en gènes et éléments transposables différentiellement exprimés entre les gonades mâles et femelles. De plus, les gènes et les éléments transposables proches le long des chromosomes ont tendance à présenter des biais d'expression similaires. Deux hypothèses, non mutuellement exclusives, peuvent rendre compte de cette observation : d'une part, les éléments transposables pourraient modifier l'expression des gènes voisins, et d'autre part, l'environnement génomique du site d'insertion pourrait influencer l'expression des éléments transposables. Les travaux réalisés ne permettent pas de trancher définitivement entre ces deux hypothèses, mais plusieurs observations sont en faveur d'un rôle régulateur de certains éléments transposables. Dans un deuxième axe et de manière complémentaire, j'ai mis en évidence des familles d'éléments transposables physiquement enrichies dans l'environnement des gènes sexe-biaisés. Une famille candidate a été étudiée plus en détail, et j'ai pu mettre en évidence dans ces éléments des sites de fixation de facteurs de transcription connus pour être impliqués dans la fonction sexuelle. Ces travaux montrent ainsi le rôle potentiel des éléments transposables dans l'évolution rapide de certains réseaux de régulation de gènes et serviront de socle pour de futures études fonctionnelles.In teleost fish, sexual reproduction and sexual gene regulatory networks are highly variable. In gonochoristic species, sex is determined either environmentally or genetically and can involve different genes depending on the species investigated. Sexual development and maintenance appear also variable in this clade. To understand the origin of this diversity, I studied the posssible impact of transposable elements on the fast evolution of gene regulatory networks related to sex in fish. Transposable elements are endogenous DNA sequences able to move or copy themselves in genomes. Even if they are often deleterious for their host, transposable elements can also carry regulatory sequences, such as transcription factor binding sites, and spread them in genomes. Their diversity in fish genomes form a source of ready-to-use regulatory sequences potentially involved in the fast evolution of some gene regulatory networks.To test this hypothesis, I used RNA sequencing data from male and female gonads of the Japanese Medaka, Oryzias latipes. First I analysed gene and transposable element expression and discovered regions of the genome enriched in sex-biased genes associated to sex-biased transposable elements. Moreover, genes and transposable elements located close on chromosomes tend to present similar expression bias between testis and ovary. Two hypothesis that are not mutually exclusive can explain this observation : either transposable element influence gene expression of neighbooring genes, or the genomic locus where the transposable element inserts influence its expression. We were not able to definitively discriminate between these two hypotheses, but our work identified several clues for a regulatory role of transposable elements. In the second part and in a complementary way I found transposable element families physically enriched near to sex-biased genes. One family was further investigated and shown to carry transcription factor binding sites involved in sexual function.This work brings new insights on the possible role of transposable elements in the fast evolution of gene regulatory networks and paves the way for future functionnal studies

Impact des éléments transposables sur l'évolution de la régulation des gènes : exemple du sexe chez les poissons téléostéens

In teleost fish, sexual reproduction and sexual gene regulatory networks are highly variable. In gonochoristic species, sex is determined either environmentally or genetically and can involve different genes depending on the species investigated. Sexual development and maintenance appear also variable in this clade. To understand the origin of this diversity, I studied the posssible impact of transposable elements on the fast evolution of gene regulatory networks related to sex in fish. Transposable elements are endogenous DNA sequences able to move or copy themselves in genomes. Even if they are often deleterious for their host, transposable elements can also carry regulatory sequences, such as transcription factor binding sites, and spread them in genomes. Their diversity in fish genomes form a source of ready-to-use regulatory sequences potentially involved in the fast evolution of some gene regulatory networks.To test this hypothesis, I used RNA sequencing data from male and female gonads of the Japanese Medaka, Oryzias latipes. First I analysed gene and transposable element expression and discovered regions of the genome enriched in sex-biased genes associated to sex-biased transposable elements. Moreover, genes and transposable elements located close on chromosomes tend to present similar expression bias between testis and ovary. Two hypothesis that are not mutually exclusive can explain this observation : either transposable element influence gene expression of neighbooring genes, or the genomic locus where the transposable element inserts influence its expression. We were not able to definitively discriminate between these two hypotheses, but our work identified several clues for a regulatory role of transposable elements. In the second part and in a complementary way I found transposable element families physically enriched near to sex-biased genes. One family was further investigated and shown to carry transcription factor binding sites involved in sexual function.This work brings new insights on the possible role of transposable elements in the fast evolution of gene regulatory networks and paves the way for future functionnal studies.Chez les poissons téléostéens, les modes de reproduction sexuée et les réseaux de régulation des gènes liés au sexe sont très variables. La détermination du sexe des espèces gonochoriques, par exemple, peut être aussi bien génétique qu'environnementale et peut impliquer des gènes différents selon les espèces. Les régulations du développement et du maintien du sexe apparaissent également variables dans ce groupe. Pour essayer de comprendre l'origine de cette diversité, je me suis intéressé à l'impact possible des éléments transposables sur la régulation de gènes liés au sexe chez ces poissons. Bien que souvent neutres, et parfois délétères pour leur hôte, les éléments transposables peuvent aussi transporter des séquences régulatrices, comme des sites de fixation de facteurs de transcription, et les disséminer à travers les génomes. Pour tester cette hypothèse, j'ai utilisé des données de séquençage d'ARN issues de gonades mâles et femelles d'Oryzias latipes, le médaka japonais. Dans un premier temps, j'ai analysé l'expression des gènes et des éléments transposables et mis en évidence des régions du génome enrichies en gènes et éléments transposables différentiellement exprimés entre les gonades mâles et femelles. De plus, les gènes et les éléments transposables proches le long des chromosomes ont tendance à présenter des biais d'expression similaires. Deux hypothèses, non mutuellement exclusives, peuvent rendre compte de cette observation : d'une part, les éléments transposables pourraient modifier l'expression des gènes voisins, et d'autre part, l'environnement génomique du site d'insertion pourrait influencer l'expression des éléments transposables. Les travaux réalisés ne permettent pas de trancher définitivement entre ces deux hypothèses, mais plusieurs observations sont en faveur d'un rôle régulateur de certains éléments transposables. Dans un deuxième axe et de manière complémentaire, j'ai mis en évidence des familles d'éléments transposables physiquement enrichies dans l'environnement des gènes sexe-biaisés. Une famille candidate a été étudiée plus en détail, et j'ai pu mettre en évidence dans ces éléments des sites de fixation de facteurs de transcription connus pour être impliqués dans la fonction sexuelle. Ces travaux montrent ainsi le rôle potentiel des éléments transposables dans l'évolution rapide de certains réseaux de régulation de gènes et serviront de socle pour de futures études fonctionnelles

Hormones et dopage

LYON1-BU Santé (693882101) / SudocSudocFranceF