Les distorteurs de ségrégation méiotiques sont des éléments génétiques égoïstes qui favorisent leur propre transmission en manipulant la méiose à leur avantage. La diffusion dans les populations d’un distorteur lié au chromosome X (Sex-Ratio) provoque un excès de femelles et cela conduit à un conflit entre le chromosome X et les autres chromosomes. Ces conflits intra-génomiques sont d’importants moteurs de l’évolution des génomes. Mais, peu de choses sont connues sur la nature moléculaire et la fonction des éléments égoïstes Sex-Ratio. Le premier chapitre de cette thèse présente une synthèse actualisée sur les distorteurs de ségrégation méiotiques liés à un chromosome sexuel. Le second chapitre est consacré à l’identification et la caractérisation d’un élément distorteur du système Sex-Ratio « Paris » de Drosophila simulans, dans lequel deux éléments distorteurs liés au chromosome X provoquent ensemble la misségrégation des chromatides sœurs du chromosome Y lors de la méiose II. J’identifie à travers une cartographie génétique par recombinaison un des loci distorteur et je conduis une validation fonctionnelle de son implication dans la distorsion. Il s’agit d’un jeune gène qui évolue rapidement et appartient à une famille de gènes bien connus, impliquée dans la constitution de l’hétérochromatine. Ce gène a émergé par duplication il y a environ 15-22 millions d’années et a connu de façon indépendante de multiples duplications en cis, pseudogenizations, ou bien directement sa perte tout au long de son histoire évolutive. Cela suggère que ce gène pourrait avoir été impliquée dans de multiples conflits génétiques. Le dernier chapitre est consacré à une étude exploratoire de la diversité structurale des chromosomes Y en relation avec la distorsion de ségrégation méiotique du système « Paris ». Les résultats présentés dans ce manuscrit contribuent à augmenter les connaissances sur l’origine moléculaire des conflits génétiques et sur leur impact évolutif. / Segregation distorters are selfish genetic elements that promote their own transmission by subverting the meiotic process to their advantage. The spread of an X-linked distorter (Sex-Ratio) in populations results in an excess of females, which triggers a genetic conflict between the X chromosome and the rest of the genome. Such conflicts are important drivers of genome evolution, but little is known about the molecular nature and the function of the Sex Ratio selfish elements. The first chapter of this manuscript is a review of the current knowledge about X-linked segregation distorters. Then, I present my work on the « Paris » Sex Ratio system of Drosophila simulans, in which two distorter elements on the X chromosome co-operate to prevent Y chromosome sister chromatids segregation during meiosis II. I mapped a gene in one of the distorter loci and achieved the functional validation of its involvement in sex-ratio distortion. It is a young and rapidly evolving gene that belongs to a well-known gene family involved in chromatin state regulation. It emerged through duplication about 15-22 Myrs ago and has experienced multiple independant cis-duplications, loss or pseudogenization throughout its evolutionary history. This suggests that this gene could have been involved in multiple genetic conflicts. Finally, the last chapter is about an opening study of the strucural diversity of Y chromosomes in relation to « Paris » segregation distorter. These findings should help understanding the molecular basis of genetic conflicts and the evolutionary impact of heterochromatin regulation during meiosis.

Selfish genetic elements can distort the sex ratios of their hosts by increasing their own transmission to the next generation in a non-mendelian fashion. These elements can be either nuclear genes on a sex chromosome or cytoplasmically inherited microbes, and achieve an increased transmission by manipulating gametogenesis or host reproduction. Often these selfish elements benefit from a female biased population (for example heritable microbes are passed on maternally in the egg cytoplasm), while non-selfish, autosomal genes are selected to produce a balanced sex ratio. These differing reproductive strategies cause a genetic conflict that results in an “evolutionary arms race” that can promote the evolutionary change of sex determination systems. In this thesis, I investigate an extreme sex ratio distortion in a species of booklouse, Liposcelis sp. This species contains two distinct female types, one of which carries a maternally transmitted selfish genetic element that results in exclusively female offspring being produced. Recently, a candidate for the sex ratio distortion was identified as a horizontally transferred bacterial gene, that we have called Odile, and that is present in the genome of the (distorter) female carrying the distorting element. The gene originates from the endosymbiotic bacterium Wolbachia that is well known for its ability to distort the sex ratio of its hosts. I investigated this horizontal gene transfer event and attempt to characterize Odile. I provide evidence that this Wolbachia gene has been integrated into the genome of the distorter females and is not a bacterial contaminant. I found that the Odile gene has been duplicated and may have been horizontally transferred from Wolbachia independently to at least three other insect genomes. Additionally, I found that Odile is transcribed at low levels in a life-stage specific manner that is suggestive of a role in development. Additionally, I looked into male mate choice in this species as one aspect of the persistence of the distorting element. I found that male Liposcelis sp. do not discriminate between the two female types and do not spend more time mating with one female type over the other. These results contribute to ongoing research into the extreme sex ratio distortion found in this species and the candidate gene that may be the cause. Selfish genetic elements are an important driver of sex determination evolution, and Liposcelis sp. provides a unique and exciting system to investigate the implications of selfish elements in a genome further. / Graduate / 2019-12-17

Selfish genes that bias their own transmission during gametogenesis can spread rapidly in populations, even if they contribute negatively to the fitness of their host. Driving X chromosomes provide a clear example of this type of selfish propagation. These chromosomes, which are found in a broad range of taxa including plants, mammals, and insects, can have important evolutionary and ecological consequences. In this thesis, I report a new case of X chromosome drive (X drive) in a widespread woodland fly, Drosophila testacea. I show that males carrying the driving X (SR males) sire 80-100% female offspring, and that the majority of sons produced by SR males are sterile and appear to lack a Y chromosome. This suggests that meiotic defects involving the Y chromosome may underlie X drive in this species. Abnormalities in sperm cysts of SR males reflect that some spermatids are failing to develop properly, confirming that drive is acting during gametogenesis. Further, I show that SR males possess a diagnostic X chromosome haplotype that is perfectly associated with the sex ratio distortion phenotype. Phylogenetic analysis of X-linked sequences from D. testacea and related species strongly suggests that the driving X arose prior to the split of D. testacea and its sister species, D. neotestacea and D. orientacea. Suppressed recombination between the XST and XSR due to inversions on the XSR likely explains their disparate evolutionary histories. By screening wild-caught flies using progeny sex ratios and a diagnostic X-linked marker, I demonstrate that the driving X is present in wild populations at a frequency of ~10% and that autosomal suppressors of drive are segregating in the same population. Both SR males and homozygous females for the driving X have reduced fertility, which helps to explain the persistence of the driving X over evolutionary timescales. The testacea species group appears to be a hotspot for X drive, and D. testacea is a promising model to compare driving X chromosomes in closely related species, some of which may even be younger than the chromosomes themselves. / Graduate / 2019-04-16

La distorsion de ségrégation méiotique est une entorse à la loi de ségrégation équilibrée des allèles via les gamètes. Les gènes ou éléments génétiques causaux (distorteurs de ségrégation) empêchent, chez les hétérozygotes, la production de gamètes qui ne les contiennent pas. Ils peuvent ainsi se répandre dans les populations même s’ils sont délétères pour les individus porteurs.Parce qu'ils induisent un biais du sexe ratio, les distorteurs liés au sexe et s'exprimant dans le sexe hétérogamétique sont générateurs de conflits intragénomiques, caractérisés par l'évolution de suppresseurs qui tendent à rétablir l'équilibre des sexes. Ce processus peut conduire à l’émergence de nouvelles espèces, à l’évolution du comportement reproducteur ou du déterminisme du sexe.Dans l'espèce Drosophila simulans, des distorteurs liés au chromosome X, perturbent la ségrégation du chromosome Y lors de la méiose mâle. La descendance des mâles porteurs est alors très majoritairement femelle. Un de ces éléments distorteurs, le gène HP1D2, code une protéine qui se lie au chromosome Y avant la méiose. La distorsion est le fait d'allèles dysfonctionnels de HP1D2 (qui ont un faible niveau de transcrits testiculaires et/ou ont une délétion du domaine d’interaction protéine-protéine). Dans les populations naturelles envahies par les distorteurs, ceux-ci se trouvent neutralisés par des suppresseurs autosomaux et des chromosomes Y résistants.Le premier volet de ma thèse a été consacré au déterminisme génétique de la suppression autosomale. Par cartographie de QTL, utilisant des lignées recombinantes consanguines, j'ai révélé la complexité de ce déterminisme : 5 QTLs avec de nombreuses relation d’épistasie.Le deuxième volet est consacré au chromosome Y, qui présente, d’importante variations phénotypiques pour la résistance aux distorteurs. Nous avons étudié ses variations moléculaires et structurales et la dynamique des Y résistants dans les populations naturelles. Le séquençage de différents chromosomes Y, résistants ou sensibles, a permis de retracer l’histoire évolutive du chromosome Y en relation avec celle des distorteurs.Le dernier volet est une étude cytologique pour comparer le comportement des formes sauvages et distortrices de la protéine HP1D2 dans les spermatogonies.Dans l’ensemble ces travaux apportent un éclairage sur les bases génétiques et moléculaires du système Paris et sur son évolution. / Meiotic drive is an infringement of the law of allele segregation into the gametes. In heterozygote individuals, the causal genes or genetic elements (meiotic drivers), prevent the production of gamete which does not contain it. Thus, they can spread through populations even if they are deleterious for the carriers.Because they induce sex-ratio bias, sex-linked drivers that are expressed in the heterogametic sex, are an important source of genetic conflict, characterized by the evolution of suppressor which tends to restore a balanced sex ratio. This process can lead to the emergence of new species, evolution of reproductive behavior or sex determination.In Drosophila simulans, X-linked meiotic drivers disturb the segregation of the Y chromosome during male meiosis. The progeny of carrier male is mainly composed of females. One of the drivers is the HP1D2 gene, which encodes a protein that binds to the heterochromatic Y chromosome. The distortion is due to dysfunctional alleles of HP1D2 (low level of expression and/or a deletion of its protein-protein interaction domain). In natural populations where the drivers have spread, they are neutralized by autosomal suppressors and resistant Y chromosomes.The first part of my thesis was focus on the genetic determinism of autosomal suppression. I performed a QTL mapping using recombinant inbreed lines which highlighted the complexity of the genetic determinism of suppression: 5 QTLs and multiple epistatic interaction.The second part is about the Y chromosome, which show important phenotypic variation in the resistance of Y chromosomes to the driver. We studied its molecular and structural variation and the dynamic of resistant Y chromosomes in natural population. The sequencing of different Y chromosomes, sensitive and resistant, allowed us to retrace the evolutionary history of the Y chromosome related to the one of the driver.The last part is a cytological study to compare the localization of the functional and the driver form of HP1D2 in spermatogonia.Generally, results presented here give a better insight regarding the genetic bases and the evolution of the multiple actors of the Paris sex ratio system.

No description available.