Une reconnaissance appropriée des parasites est essentielle pour une réponse immunitaire efficace, assurant l'activation adéquate des mécanismes de défense immunitaire. Chez les vertébrés, il a été démontré que les gènes codant pour les récepteurs de l'immunité adaptative impliqués dans la reconnaissance des agents pathogènes sont soumis à une intense pression sélective. En revanche, beaucoup moins d’études se sont intéressées à la sélection agissant sur les récepteurs de l'immunité innée. Le but de cette thèse est de décrire la variabilité naturelle des gènes de l'immunité innée impliqués dans la détection des agents pathogènes chez les rongeurs et d’analyser les mécanismes responsables de leur évolution. Ce travail s’est focalisé principalement sur les rongeurs de la sous-famille des Murinae et de leur rôle potentiel en tant que réservoirs d’agents pathogènes dangereux pour l’Homme. Tout d´abord nous avons étudié la variabilité intraspécifique de cinq Toll-like récepteurs ciblant les bactéries (TLR1, TLR2, TLR4, TLR5 et TLR6) pour des lignées consanguines de souris domestiques issues d’une population sauvage de deux sous-espèces : Mus musculus domesticus (Mmd) et Mus musculus musculus (Mmm). Les souches consanguines constituent un outil adapté à l'étude de la variabilité des gènes immunitaires car elles confèrent une information sur les allèles présents dans les populations naturelles tout en bénéficiant de génotypes homozygotes. Les résultats les plus significatifs concernent la découverte d'un codon stop dans l'exon 2 du Tlr5 chez une lignée de Mmm et l’absence de variabilité du Tlr4 chez Mmd. A la suite de ces résultats, nous avons décidé de vérifier si l‘absence de polymorphisme du Tlr4 chez Mmd reflète une absence de variabilité dans les populations naturelles, ou si il s’agit plutôt d’un effet de l'échantillonnage ou des croisements ultérieurs. Nous avons donc séquencé le gène Tlr4 pour les deux sous-espèces provenant de la région du Paléarctique Occidentale (au total 39 Mmm et 62 Mmd) puis nous avons comparé ces résultats avec la variabilité génétique d’un gène mitochondrial (cytochrome b). Nous avons confirmé notre prédiction : la variabilité de Tlr4 chez Mmd est fortement réduite par rapport à Mmm, probablement à cause d’agents pathogènes ayant exercé une sélection purifiante chez Mmd durant la colonisation vers l’ouest. Cependant, l'influence de mécanismes évolutifs neutres, tel que la dérive consécutive à un goulot d’étranglement démographique, ne peut être exclue sur la base de nos données. La dernière partie a été consacrée à la comparaison interspécifique de deux récepteurs : TLR4 et TLR7. Ces deux TLRs se différencient à la fois par leur localisation et leur capacité de détection. TLR4 est un TLR extracellulaire reconnaissant principalement les ligands bactériens, essentiellement les lipopolysaccharides, tandis que TLR7 est localisé dans la cellule et détecte les virus à ARN simple brin. L‘objectif était de décrire la variabilité inter-spécifique de chaque récepteur et de révéler les mécanismes de sélection s’exerçant sur ces gènes au cours de leur évolution sur une échelle de temps plus importante. Nous avons analysé 23 espèces de Murinae provenant surtout d’Asie. Nos résultats suggèrent que la sélection purifiante est la force principale ayant agit sur l’évolution des deux TLRs. Cependant, nous avons également mis en évidence des épisodes de sélection diversifiante qui ont pu être à l’origine des variations intra-spécifiques de TLRs observée aujourd’hui chez les rongeurs. Des sites sous sélection positive sont principalement concentrés dans les domaines extracellulaires des deux récepteurs, domaines responsables de la reconnaissance des agents pathogènes. Enfin, la comparaison entre ces deux TLRs montre que le TLR7 est soumis à une sélection négative plus forte. Cette sélection peut s’expliquer en raison des interactions du TLR7 avec les acides nucléiques viraux. / Appropriate recognition of parasites is crucial for effective immune response, ensuring activation of adequate defence mechanisms. In vertebrates, it has frequently been demonstrated that genes encoding proteins involved in pathogen recognition by an adaptive immune system are often subject to intense selection pressures. On the contrary, much less information has been provided on the evolution of recognition mechanisms of innate immunity. The aim of this thesis is to describe the pattern of natural variation of innate immunity genes involved in pathogen recognition in rodents and to analyze the mechanisms of their evolution. We used murine rodents (subfamily Murinae) as a principal model group because they are potential reservoirs of various pathogens dangerous to humans. First, we studied the intraspecific variability of five bacterial sensing Toll-like receptors (TLR1, TLR2, TLR4, TLR5, and TLR6) in inbred strains derived from two subspecies of the house mouse (M. m. musculus, hereafter abbreviated as Mmm and Mus musculus domesticus, Mmd). Wild-derived inbred strains are suitable tools for studying variation of immunity genes because they provide information about alleles that occur in natural populations, and at the same time they occur at homozygous state. The most significant results include the findings of a stop codon in exon 2 of the Tlr5 gene in one Mmm strain and no variability in Tlr4 of Mmd. Following these results we decided to check whether the absence of Tlr4 polymorphism in Mmd reflects the pattern found in natural populations, or whether it is a consequence of insufficient sampling or subsequent breeding. We therefore sequenced Tlr4 in both subspecies across a large part of the Western Palearctic region (in total 39 Mmm and 62 Mmd individuals), then we compared these results with variability on mitochondrial DNA (cytochrome b). The result confirmed our prediction that observed variability in Mmd is strongly reduced also in free-living populations (compared to Mmm), probably due to strong purifying selection by pathogens with which they met during the westward colonization. However, the influence of random evolutionary processes (e.g. drift during bottlenecks) cannot be excluded based on our data. At the intraspecific level, we could not find any sign of positive selection. The last part of my dissertation is devoted to interspecific comparison of two receptors, TLR4 and TLR7. These two TLRs differ in the exposure and the ligands detection. TLR4 is an extracellular receptor detecting mainly bacterial ligands (especially lipopolysaccharides), while TLR7 is located inside the cell and detects ssRNA viruses. The aim of this part of the thesis was to describe variability of both receptors at the interspecific level and to reveal selection forces acting on TLRs in longer evolutionary time scale. In total we analyzed 23 rodent species of the subfamily Murinae in Europe, Asia and Africa. Our results suggest that purifying selection has been a dominant force in evolution of the Tlr4 and Tlr7 genes, but we also demonstrated that episodic diversifying selection has shaped the present species-specific variation in rodent Tlrs. Sites under positive selection were concentrated mainly in the extracellular domain of both receptors, which is responsible for ligand binding. The comparison between two TLRs lead us to the conclusion that the intracellular TLR7 is under much stronger negative selection pressure, presumably due to its interaction with viral nucleic acids.

As tartarugas marinhas são répteis de vida longa que realizam extensas migrações entre áreas de alimentação e desova, resultando em estágios sucessivos de mistura e isolamento de estoques genéticos, espacial e temporalmente. A tartaruga-verde (Chelonia mydas) está ameaçada de extinção, e é fundamental entender sua dinâmica populacional e distribuição para o manejo e conservação da espécie. O objetivo deste estudo foi analisar a diversidade genética, estrutura populacional, origens dos indivíduos e história demográfica de C. mydas em três locais do Oceano Atlântico (estado do Rio de Janeiro, Brasil - área de alimentação; Guadalupe e Guiana Francesa - áreas de desova), com base em sequências da região controle do DNA mitocondrial (mtDNA) e 10 loci de microssatélites. As análises de mtDNA demonstraram que a área amostrada no Brasil tem perfil genético semelhante às outras áreas de alimentação da costa brasileira. De maneira semelhante, o perfil genético das duas áreas de desova é bastante similar ao de outros sítios reprodutivos na região do Caribe. As análises de estoque misto revelaram que os indivíduos juvenis no Brasil são provenientes principalmente da Ilha Ascensão, Guiana Francesa e Guiné Bissau. Os microssatélites detectaram estrutura genética entre as três populações, apesar de haver um fluxo de migrantes entre elas, especialmente de indivíduos da Guiana Francesa em direção ao Brasil e Guadalupe. Guiana Francesa, Guadalupe e Brasil apresentaram declínio populacional severo, detectado pelos microssatélites. Apesar da distribuição global, as populações de tartarugas-verdes estão sujeitas a diferentes pressões nos habitats que ocupam, e é importante entender quais populações estão ameaçadas. Este estudo enfatiza a importância da conectividade entre áreas de alimentação e desova que podem estar amplamente distribuídas de acordo com oportunidades ou restrições ecológicas, adicionando informações a respeito da dispersão e a dinâmica de tartarugas-verdes que frequentam o Oceano Atlântico / Sea turtles are reptiles with a long lifespan that undertake wide-ranging migrations through feeding and nesting sites, resulting in successive stages of mixing and isolating genetic stocks, both spatially and temporally. The green sea turtle (Chelonia mydas) is threatened with extinction, and it is essential to understand its population dynamics and distribution in order to manage and preserve the species. The aim of this study was to analyze the genetic diversity, population structure, natal origins and demographic history of C. mydas in three sites in the Atlantic Ocean (Rio de Janeiro state, Brazil - feeding ground; Guadeloupe and French Guiana - nesting sites), based on sequences of the mitochondrial DNA (mtDNA) control region and 10 microsatellites loci. The mtDNA analyses demonstrated that Brazilian samples have the same genetic profile of others collected in feeding grounds in the Brazilian coast. Similarly, the genetic profile of the nesting sites has resemblances to others in the Caribbean region. The mixed stock analyses revealed that most of the juveniles in Rio de Janeiro state come from Ascension Island, French Guiana and Guinea Bissau. Microsatellites detected genetic structure among the three populations, even with migration flows, especially in individuals from French Guiana to Brazil and Guadeloupe. French Guiana, Guadeloupe and Brazil presented a severe population decline, detected by the microsatellites analyses. Despite the worldwide distribution, green sea turtle populations undergo different pressures at the habitats they occupy, and it is important to understand which populations are threatened. This study emphasizes the importance of connecting nesting and feeding areas that can be widely distributed according to ecological opportunities or constraints, adding information on dispersion and population dynamics of green sea turtles on Atlantic Ocean

As tartarugas marinhas são répteis de vida longa que realizam extensas migrações entre áreas de alimentação e desova, resultando em estágios sucessivos de mistura e isolamento de estoques genéticos, espacial e temporalmente. A tartaruga-verde (Chelonia mydas) está ameaçada de extinção, e é fundamental entender sua dinâmica populacional e distribuição para o manejo e conservação da espécie. O objetivo deste estudo foi analisar a diversidade genética, estrutura populacional, origens dos indivíduos e história demográfica de C. mydas em três locais do Oceano Atlântico (estado do Rio de Janeiro, Brasil - área de alimentação; Guadalupe e Guiana Francesa - áreas de desova), com base em sequências da região controle do DNA mitocondrial (mtDNA) e 10 loci de microssatélites. As análises de mtDNA demonstraram que a área amostrada no Brasil tem perfil genético semelhante às outras áreas de alimentação da costa brasileira. De maneira semelhante, o perfil genético das duas áreas de desova é bastante similar ao de outros sítios reprodutivos na região do Caribe. As análises de estoque misto revelaram que os indivíduos juvenis no Brasil são provenientes principalmente da Ilha Ascensão, Guiana Francesa e Guiné Bissau. Os microssatélites detectaram estrutura genética entre as três populações, apesar de haver um fluxo de migrantes entre elas, especialmente de indivíduos da Guiana Francesa em direção ao Brasil e Guadalupe. Guiana Francesa, Guadalupe e Brasil apresentaram declínio populacional severo, detectado pelos microssatélites. Apesar da distribuição global, as populações de tartarugas-verdes estão sujeitas a diferentes pressões nos habitats que ocupam, e é importante entender quais populações estão ameaçadas. Este estudo enfatiza a importância da conectividade entre áreas de alimentação e desova que podem estar amplamente distribuídas de acordo com oportunidades ou restrições ecológicas, adicionando informações a respeito da dispersão e a dinâmica de tartarugas-verdes que frequentam o Oceano Atlântico / Sea turtles are reptiles with a long lifespan that undertake wide-ranging migrations through feeding and nesting sites, resulting in successive stages of mixing and isolating genetic stocks, both spatially and temporally. The green sea turtle (Chelonia mydas) is threatened with extinction, and it is essential to understand its population dynamics and distribution in order to manage and preserve the species. The aim of this study was to analyze the genetic diversity, population structure, natal origins and demographic history of C. mydas in three sites in the Atlantic Ocean (Rio de Janeiro state, Brazil - feeding ground; Guadeloupe and French Guiana - nesting sites), based on sequences of the mitochondrial DNA (mtDNA) control region and 10 microsatellites loci. The mtDNA analyses demonstrated that Brazilian samples have the same genetic profile of others collected in feeding grounds in the Brazilian coast. Similarly, the genetic profile of the nesting sites has resemblances to others in the Caribbean region. The mixed stock analyses revealed that most of the juveniles in Rio de Janeiro state come from Ascension Island, French Guiana and Guinea Bissau. Microsatellites detected genetic structure among the three populations, even with migration flows, especially in individuals from French Guiana to Brazil and Guadeloupe. French Guiana, Guadeloupe and Brazil presented a severe population decline, detected by the microsatellites analyses. Despite the worldwide distribution, green sea turtle populations undergo different pressures at the habitats they occupy, and it is important to understand which populations are threatened. This study emphasizes the importance of connecting nesting and feeding areas that can be widely distributed according to ecological opportunities or constraints, adding information on dispersion and population dynamics of green sea turtles on Atlantic Ocean