La tesi que teniu a les mans recull quatre treballs amb un objectiu comú; determinar si els patògens (virus, bacteris, paràsits.) han exercit pressions selectives sobre els genomes dels seus hostes (com per exemple els humans).Sabent que la detecció de l'empremta de la selecció permet identificar aquelles regions del genoma que han estat rellevants al llarg de l'evolució d'una espècie, ja que a nivell local és la variació funcional qui acaba essent objecte de la selecció, ens hem disposat a estudiar els possibles senyals de selecció en gens relacionats amb la interacció hoste-patògen. En concret, hem analitzat gens que codifiquen per: a) components del sistema immunitari innat i, b) enzims de glicosilació, la majoria dels quals s'inclouen en quatre de les principals rutes biosintètiques de glicans, en diferents poblacions humanes.Com a conclusió principal; ambdós conjunts de gens mostren clars senyals de selecció. A més hem vist que segons el context biològic on és troben certs gens és veuen més afectats per l'acció de la selecció natural. / The present thesis includes four studies with a common objective: determining whether pathogens (virus, bacteria, parasites.) have exerted selective pressures on the genome of their hosts (for example, humans).Detecting signatures of positive selection is a useful tool to identify functionally relevant genomic regions since selection locally shapes the functional variation. Based on this premise, we have studied the possible signatures of selection in genes related to host-pathogen interactions. Specifically, we have analyzed those genes encoding: a) components of the innate immunity response; and ii) glycosylation enzymes most of them involved in four major glycan biosynthesis pathways, in different human populations.The main conclusion obtained from these studies is that both studied gene categories show clear signatures of selection. Moreover, we have determined that according to their biological context certain genes are more prone to the action of selection.

O palmiteiro (Euterpe edulis Mart.) é uma espécie nativa da Mata Atlântica cujas populações naturais encontram-se degradadas pelo extrativismo. Considerando a escassez de informações relativas às conseqüências genéticas da exploração de palmito, o objetivo deste estudo foi avaliar o impacto do processo de exploração sobre os níveis de diversidade, estrutura genética e tamanho efetivo de populações da espécie. Também foram estudados aspectos genéticos do recrutamento de plantas e o sistema reprodutivo da espécie. O estudo foi realizado em duas localidades do Estado de Santa Catarina, nos municípios de São Pedro de Alcântara e Ibirama. Em cada localidade foram escolhidas duas áreas de ocorrência natural de E. edulis, uma sem influência antrópica e outra que sofreu exploração de palmito, totalizando quatro populações. Os sistemas de exploração foram: (i) extrativismo - onde todos os indivíduos acima de 2 m de altura são cortados, incluindo plantas reprodutivas; and (ii) manejo - onde somente indivíduos acima de 9 cm de DAP são cortados, com a manutenção de 50 plantas reprodutivas por hectare. Em cada população foram examinadas plântulas, jovens e adultos, usando oito locos microssatélites e dez locos alozímicos. Os resultados revelaram que a espécie se reproduz por alogamia ( m tˆ = 0,996 para microssatélites e m tˆ = 1,000 para isoenzimas), porém a ocorrência de cruzamentos entre indivíduos aparentados (até 5%) e cruzamentos biparentais (10%) indica a ocorrência de cruzamentos não aleatórios. Em locos alozímicos, observaram-se as seguintes amplitudes de variação das estimativas de diversidade entre as categorias: Aˆ : 3,05 a 3,15; e Hˆ : 0,416 a 0,431; o Hˆ : 0,378 a 0,403. Em locos microssatélites, a variação observada foi a seguinte: Aˆ : 14,12 a 14,72; e Hˆ : 0,781 a 0,785; o Hˆ : 0,678 a 0,709. Nas populações não exploradas, houve um aumento na freqüência de heterozigotos na direção do estádio adulto, o que sugere a ação da seleção favorecendo o aumento de heterozigotos. Valores altos e significativos do índice de fixação ( fˆ ) foram observados, especialmente nos marcadores microssatélites, indicando desvios do equilíbrio de Hardy-Weinberg. De modo geral, ambos os marcadores revelaram um aumento dos valores de fˆ nas populações exploradas, especialmente entre as plântulas. As estimativas ST Gˆ e ST Rˆ não revelaram alterações na estrutura genética das populações exploradas e demostraram uma divergência genética inferior a 5% na maioria das comparações aos pares, em ambos os marcadores. O tamanho efetivo ( e Nˆ ) dos indivíduos adultos por hectare foi superior a 110 nas populações não pertubadas, enquanto nas populações exploradas, o tamanho efetivo por hectare foi reduzido para 45, sob manejo, e 14, sob extrativismo. Porém, o tamanho efetivo total das populações exploradas ainda é elevado, o que explica a manutenção dos altos níveis de diversidade nessas populações. Finalmente, a informação genética conjunta desses marcadores demonstrou que os efeitos da exploração foram pouco pronunciados até o momento em relação aos níveis de diversidade e estrutura genética das populações de E. edulis. Entretanto, a redução da população de cruzamentos resultou em alterações no comportamento reprodutivo dos indivíduos, promovendo um aumento nos níveis de endogamia nas coortes mais jovens das populações exploradas. Contudo, os resultados obtidos neste estudo indicaram questões adicionais a serem estudadas. Em função do elevado nível de variabilidade dos locos microssatélites observado em E. edulis, recomenda-se aumentar o tamanho das amostras visando otimizar a informação genética proporcionada por esses marcadores. Além disso, novos estudos são necessários sobre os efeitos do manejo tecnificado, uma vez que os resultados obtidos podem ter sido influenciados por outros eventos de exploração ocorridos no passado e pelas populações existentes nas proximidades devido ao elevado fluxo gênico da espécie. / Heart-of-palm tree (Euterpe edulis Mart.; Arecaceae) is a native species of the Atlantic forest whose natural populations are degraded by extractivism. Regarding the relative scarcity of information on the genetic consequences of palm heart exploitation, the aim of this study was to investigate the effects of two exploitation systems - extractivism and management - on the levels of variability, genetic structure and effective size of Euterpe edulis Mart. populations. We also investigated genetic aspects of the plant recruitment and the reproductive system of the species. Four natural populations of E. edulis with different histories of disturbance were surveyed in the districts of São Pedro de Alcântara and Ibirama, Santa Catarina, Brazil. At both sites, we sampled an undisturbed and an exploited population. The exploitation systems were: (i) extractivism - where most individuals higher than 2 m are harvested, including reproductive plants; and (ii) management - where only individuals with more than 9 cm of DBH are harvested, with the maintainance of 50 reproductive plants per ha. Three categories of plants, from seedlings to adults, were examined using eight microsatellite loci and ten allozyme loci. Results demonstrated the preferentially allogamic behaviour of the species ( m tˆ = 0.996 for microsatellites and m tˆ = 1.000 for allozymes), but the occurrence of matings among related individuals (5%) and biparental matings (10%) indicated the existence of non-random matings in this species. For allozymic loci, the following diversity estimates were obtained among the categories: Aˆ : 3.05 to 3.15; e Hˆ : 0.416 to 0.431; o Hˆ : 0.378 to 0.403. For microsatellites, the estimates were as follows: Aˆ : 14.12 to 14.72; e Hˆ : 0.781 to 0.785; o Hˆ : 0.678 to 0.709. In undisturbed populations, there was an increase in heterozygote frequency towards the adult stages, suggesting the action of natural selection favouring such heterozygote increase. Highly significant values of fixation index ( fˆ ) were observed, mainly at microsatellite loci, indicating departures from Hardy-Weinberg expectation. Both markers displayed an increase of fˆ values in the exploited populations, especially for seedlings. The estimates of interpopulation genetic variation ( ST Gˆ ; ST Rˆ ) revealed that more than 95% of the molecular genetic variability of the species is distributed within populations, and there was no evidence of changes in genetic structure of the exploited populations. Effective size ( e Nˆ ) per hectare of the adult individuals was higher than 110 in the two undisturbed populations, while in the exploited populations the effective size per hectare was reduced to 45 under management, and 14 under extractivism. However, the total effective size of the exploited populations was still high, which explains the maintenance of high diversity levels in these populations. Finally, the genetic information from both markers displayed small pronounced effects of the exploitation process on variability and population genetic structure of E. edulis, with the exception of an increase in the inbreeding levels among seedlings and juveniles of the exploited populations. However, our results raised further questions for study. Because of the hypervariability of microssatellite loci used in this work, we would recommend an increase in the sample size (>100) in order to optimize the genetic information provided by these markers. Moreover, new investigations are necessary on the effects of management, since the results from this study could have been influenced by other exploitation events that have occurred in the past and by the existence, due to the high gene flow of the species, of surrounding undisturbed populations.

L’utilisation de variétés de plantes porteuses de gènes majeurs de résistance a longtemps été une solution privilégiée pour lutter contre les maladies des plantes. Cependant, la capacité des agents pathogènes à s’adapter à ces variétés après seulement quelques années de culture rend nécessaire la recherche de résistances à la fois efficaces et durables. Les objectifs de cette thèse étaient (i) d’identifier chez la plante des régions génomiques contraignant l’évolution des agents pathogènes en induisant des effets de dérive génétique et (ii) d’étudier l’impact des forces évolutives induites par la plante sur la capacité d’adaptation des pathogènes aux résistances variétales, l’ambition étant par la suite d’employer au mieux ces forces pour limiter l’évolution des pathogènes. Le pathosystème piment (Capsicum annuum) – PVY (Potato virus Y) a été principalement utilisé pour mener ces travaux de recherche. Afin de répondre au premier objectif, une cartographie de QTL (quantitative trait loci) sur une population biparentale de piment et une étude de génétique d’association sur une core-collection de piments ont été réalisées. Ces deux approches ont permis de mettre en évidence des régions génomiques sur les chromosomes 6, 7 et 12 impliquées dans le contrôle de la taille efficace des populations virales lors de l’étape d’inoculation du virus dans la plante. Certains de ces QTL ont montré une action vis-à-vis du PVY et du CMV (Cucumber mosaic virus) tandis que d’autres se sont révélés être spécifiques d’une seule espèce virale. Par ailleurs,le QTL détecté sur le chromosome 6 co-localise avec un QTL précédemment identifié comme contrôlant l’accumulation virale et interagissant avec un QTL affectant la fréquence de contournement d’un gène majeur de résistance. Pour répondre au second objectif, une analyse de la corrélation entre l’intensité des forces évolutives induites par la plante et une estimation expérimentale de la durabilité du gène majeur a été réalisée. De l’évolution expérimentale de populations de PVY sur des plantes induisant des effets de dérive génétique, de sélection et d’accumulation virale contrastés a également été effectuée. Ces deux études ont démontré qu’une plante induisant une forte dérive génétique associée à une réduction de l’accumulation virale permettait de contraindre l’évolution des populations virales, voire d’entraîner leur extinction. Ces résultats ouvrent de nouvelles perspectives pour le déploiement de déterminants génétiques de la plante qui influenceraient directement le potentiel évolutif du pathogène et permettraient de préserver la durabilité des gènes majeurs de résistance. / Plants carrying major resistance genes have been widely used to fight against diseases. However, the pathogensability to overcome the resistance after a few years of usage requires the search for efficient and durable resistances.The objectives of this thesis were (i) to identify plant genomic regions limiting pathogen evolution by inducinggenetic drift effects and (ii) to study the impact of the evolutionary forces imposed by the plant on the pathogenability to adapt to resistance, the goal being to further use these forces to limit pathogen evolution. The pepper(Capsicum annuum) – PVY (Potato virus Y) pathosystem has been mainly used to conduct these researches.Regarding the first objective, quantitative trait loci (QTL) were mapped on a biparental pepper population andthrough genome-wide association on a pepper core-collection. These approaches have allowed the detection ofgenomic regions on chromosomes 6, 7 and 12 controlling viral effective population size during the inoculationstep. Some of these QTLs were common to PVY and CMV (Cucumber mosaic virus) while other were virusspecific.Moreover, the QTL detected on chromosome 6 colocalizes with a previously identified QTL controllingPVY accumulation and interacting with a QTL affecting the breakdown frequency of a major resistance gene.Regarding the second objective, a correlation analysis between the evolutionary forces imposed by the plant andan experimental estimation of the durability of a major resistance gene has been done. Experimental evolution ofPVY populations on plants contrasted for the levels of genetic drift, selection and virus accumulation they imposedhas also been performed. Both studies demonstrated that a plant inducing a strong genetic drift combined to areduction in virus accumulation limits virus evolution and could even lead to the extinction of the virus population.These results open new perspectives to deploy plant genetic factors directly controlling pathogen evolutionarypotential and could help to preserve the durability of major resistance genes.

Les systèmes reproducteurs déterminent comment le matériel génétique est transmis d’une génération à la suivante […]. Les espèces qui combinent de la reproduction sexuée et asexuée/clonale sont très répandues [… mais] l’effet de leur système reproducteur sur leur évolution reste énigmatique et discuté.L’objectif de cette thèse est de modéliser la dynamique des fréquences génotypiques d’une population avec une combinaison de reproduction sexuée et/ou clonale dans des cycles de vie principalement diploïdes [. … Un] modèle du type chaine de Markov avec temps et états discrets sert de base mathématique pour décrire [leurs] changements […] au cours du temps.Les résultats montrent que la reproduction partiellement asexuée peut en effet modifier la dynamique de la diversité génomique par rapport à une reproduction strictement sexuée ou strictement asexuée. […] L’histoire démographique a un rôle important pour les organismes partiellement clonaux et doit être prise en compte dans toute analyse […].Cette thèse fait des recommandations pour la collecte des données et une hypothèse de base pour l’interprétation des données de génétique/génomique […]. Ces résultats ont des retombées dans plusieurs domaines, allant de la recherche fondamentale […] à des applications en agriculture […], pêche […] et protection de la nature […]. / Reproductive systems determine how genetic material is passed from one generation to the next, making them an important factor for evolution. Organisms that combine sexual and asexual/clonal reproduction are very widespread [… yet] the effects of their reproductive system on their evolution are still controversial and poorly understood.The aim of this thesis was to model the dynamics of genotype frequencies under combined sexual/clonal reproduction in dominantly diploid life cycles [. … A] state and time discrete Markov chain model served as the mathematical basis to describe [their] changes […] through time.The results demonstrate that partial clonality may indeed change the dynamics of genomic diversity compared to either exclusively sexual or exclusively clonal populations. […] Time has a crucial role in partially clonal populations and needs to be taken into account in any analysis of their genomic diversity.This thesis provides recommendations for data collection and a null hypothesis for the interpretation of population genetic/genomic data […]. Moreover, it includes new methods for the analysis of genotype-based population genetic Markov chain models. These results have a high potential relevance in several areas, ranging from basic research […] to applications in agriculture […], fisheries […] and nature conservation […].

La gestion durable des variétés génétiquement résistantes aux pathogènes des cultures nécessite de tenir compte de leurs capacités évolutives. Celles-ci découlent de leur histoire évolutive et de la dynamique actuelle de leurs populations qui peut être modifiée par les activités humaines inhérentes au milieu agricole. La description et l’évaluation des capacités évolutives d’un pathogène ne sont donc possibles que sur des populations issues d’environnements non soumis à des perturbations d’origine anthropique. Les objectifs de ce travail sont donc (1) de reconstruire les histoires évolutives de deux nématodes à kystes, Heterodera schachtii et Heterodera betae et de leur hôte sauvage commun, Beta vulgaris ssp. maritima, à partir de populations sauvages distribuées sur le littoral du sud de l’Espagne à la Suède ; (2) de décrire, à une échelle plus fine, le fonctionnement et la structure génétique de populations sauvages d’H. schachtii.Nos résultats montrent que la colonisation de la côte Atlantique par les deux nématodes a probablement été influencée par les fluctuations climatiques survenues depuis le dernier Maximum Glaciaire et les courants marins. Les patrons phylogéographiques observés entre H. schachtii et la plante suggèrent des histoires évolutives disjointes contrairement à ceux observés chez H. betae. A fine échelle spatiale, les populations d’H. schachtii sont isolées entre elles, structurées à l’échelle de la plante hôte et présentent de petites tailles efficaces. Ces résultats sont discutés dans le contexte général de la protection des cultures. / The sustainable management of genetic resistances to crop pathogens needs to consider their evolutionary potential. The evolutionary potential results both from the evolutionary history and the current population dynamics of pathogens, which can be affected by human activities occurring in agro-ecosystems. Therefore, they should be described and evaluated on wild pathogen populations free of human-mediated disturbances. The aim of this work is twofold (1) assessing the evolutionary history of two cysts nematodes, Heterodera schachtii and Heterodera betae, and their common wild host, Beta vulgaris ssp. maritima, in wild populations sampled on the coast from the South of Spain to Sweden; (2) investigating at a fine spatial scale the population genetic structure of H. schachtii .Results show that the colonization of the Atlantic coastline by the two nematodes was probably influenced by climatic fluctuations occurring since the Last Glacial Maximum, along with marine currents. Phylogeographical patterns of H. schachtii and the host-plant suggest a non-shared evolutionary history, which contrasts with the coastal recolonization of Europe observed in H. betae. The fine-scale study evidenced that wild populations of H. schachtii are genetically sub-structured at the level of the host plant, strongly isolated and characterized by small effective population sizes. All these results are discussed in the framework of the sustainable management of nematodes populations in cultivated fields.

<p>  </p> <p>Evolution is the foundation for all of biology. However, our approaches and understanding of evolution—simply, the change of allele frequencies from one generation to the next—have themselves evolved over time. In this dissertation I explore multiple approaches to understand evolution and the consequences of evolution across variable scales and study organisms. First, I use meta-analytic techniques and Bayesian hierarchical models to investigate the phenotypic consequences of two forms of cryptic local adaptation, co- and countergradient variation, by leveraging a decades-old quantitative genetics approach (Chapter 1). I find large effects for both co- and countergradient variation, however they are obscured in natural settings by concurrent large environmental effects. I also show that these large effects are ubiquitous across phenotypic traits, organisms, and environmental gradients, suggesting that while similar phenotypes may be the evolutionary end point, the mechanisms to achieve those phenotypes likely vary. In the following chapter I explore the rapid evolution of a unique and understudied species introduction, pink salmon (<em>Oncorhynchus gorbuscha</em>) in the Great Lakes. Pink salmon were introduced into Lake Superior in a single introduction event and have broken two obligate life histories, anadromy (though they treat the Great Lakes like surrogate oceans) and their fixed two-year life cycle, making them ripe subjects for contemporary evolution. Using whole-genome sequence data, I first investigate the effects of a genetic drift in the form of a bottleneck at introduction and characterize the subsequent loss of genetic diversity (Chapter 2). I show that despite a large loss of genetic diversity, pink salmon also rapidly adapted to their novel environment based on signals of putative selection across numerous regions of the genome, particularly in a period gene associated with their daily circadian clock (<em>per2</em>). Next, I explore how genome structure likely aided adaptation by pink salmon to the Great Lakes, providing evidence that a supergene (~29 Mbp) containing an inversion on chromosome 10 swept to near fixation in the Great Lakes (Chapter 3) and likely aided in osmoregulatory adaptation to this novel environment. Finally, I end with a short perspective chapter (Chapter 4) where I highlight potential future research directions for each of the previous chapters. Together, this research investigates the drivers and consequences of evolution across multiple scales and shows the powerful effect of genetic drift and genetic adaptation in shaping the genomic and phenotypic attributes of populations.</p>

My thesis addresses a systematic approach to stochastic models in population genetics; in particular, the Wright-Fisher models affected only by the random genetic drift. I used various mathematical methods such as Probability, PDE, and Geometry to answer an important question: \"How do genetic change factors (random genetic drift, selection, mutation, migration, random environment, etc.) affect the behavior of gene frequencies or genotype frequencies in generations?”. In a Hardy-Weinberg model, the Mendelian population model of a very large number of individuals without genetic change factors, the answer is simple by the Hardy-Weinberg principle: gene frequencies remain unchanged from generation to generation, and genotype frequencies from the second generation onward remain also unchanged from generation to generation. With directional genetic change factors (selection, mutation, migration), we will have a deterministic dynamics of gene frequencies, which has been studied rather in detail. With non-directional genetic change factors (random genetic drift, random environment), we will have a stochastic dynamics of gene frequencies, which has been studied with much more interests. A combination of these factors has also been considered. We consider a monoecious diploid population of fixed size N with n + 1 possible alleles at a given locus A, and assume that the evolution of population was only affected by the random genetic drift. The question is that what the behavior of the distribution of relative frequencies of alleles in time and its stochastic quantities are. When N is large enough, we can approximate this discrete Markov chain to a continuous Markov with the same characteristics. In 1931, Kolmogorov first introduced a nice relation between a continuous Markov process and diffusion equations. These equations called the (backward/forward) Kolmogorov equations which have been first applied in population genetics in 1945 by Wright. Note that these equations are singular parabolic equations (diffusion coefficients vanish on boundary). To solve them, we use generalized hypergeometric functions. To know more about what will happen after the first exit time, or more general, the behavior of whole process, in joint work with J. Hofrichter, we define the global solution by moment conditions; calculate the component solutions by boundary flux method and combinatorics method. One interesting property is that some statistical quantities of interest are solutions of a singular elliptic second order linear equation with discontinuous (or incomplete) boundary values. A lot of papers, textbooks have used this property to find those quantities. However, the uniqueness of these problems has not been proved. Littler, in his PhD thesis in 1975, took up the uniqueness problem but his proof, in my view, is not rigorous. In joint work with J. Hofrichter, we showed two different ways to prove the uniqueness rigorously. The first way is the approximation method. The second way is the blow-up method which is conducted by J. Hofrichter. By applying the Information Geometry, which was first introduced by Amari in 1985, we see that the local state space is an Einstein space, and also a dually flat manifold with the Fisher metric; the differential operator of the Kolmogorov equation is the affine Laplacian which can be represented in various coordinates and on various spaces. Dynamics on the whole state space explains some biological phenomena.

My thesis addresses a systematic approach to stochastic models in population genetics; in particular, the Wright-Fisher models affected only by the random genetic drift. I used various mathematical methods such as Probability, PDE, and Geometry to answer an important question: \"How do genetic change factors (random genetic drift, selection, mutation, migration, random environment, etc.) affect the behavior of gene frequencies or genotype frequencies in generations?”. In a Hardy-Weinberg model, the Mendelian population model of a very large number of individuals without genetic change factors, the answer is simple by the Hardy-Weinberg principle: gene frequencies remain unchanged from generation to generation, and genotype frequencies from the second generation onward remain also unchanged from generation to generation. With directional genetic change factors (selection, mutation, migration), we will have a deterministic dynamics of gene frequencies, which has been studied rather in detail. With non-directional genetic change factors (random genetic drift, random environment), we will have a stochastic dynamics of gene frequencies, which has been studied with much more interests. A combination of these factors has also been considered. We consider a monoecious diploid population of fixed size N with n + 1 possible alleles at a given locus A, and assume that the evolution of population was only affected by the random genetic drift. The question is that what the behavior of the distribution of relative frequencies of alleles in time and its stochastic quantities are. When N is large enough, we can approximate this discrete Markov chain to a continuous Markov with the same characteristics. In 1931, Kolmogorov first introduced a nice relation between a continuous Markov process and diffusion equations. These equations called the (backward/forward) Kolmogorov equations which have been first applied in population genetics in 1945 by Wright. Note that these equations are singular parabolic equations (diffusion coefficients vanish on boundary). To solve them, we use generalized hypergeometric functions. To know more about what will happen after the first exit time, or more general, the behavior of whole process, in joint work with J. Hofrichter, we define the global solution by moment conditions; calculate the component solutions by boundary flux method and combinatorics method. One interesting property is that some statistical quantities of interest are solutions of a singular elliptic second order linear equation with discontinuous (or incomplete) boundary values. A lot of papers, textbooks have used this property to find those quantities. However, the uniqueness of these problems has not been proved. Littler, in his PhD thesis in 1975, took up the uniqueness problem but his proof, in my view, is not rigorous. In joint work with J. Hofrichter, we showed two different ways to prove the uniqueness rigorously. The first way is the approximation method. The second way is the blow-up method which is conducted by J. Hofrichter. By applying the Information Geometry, which was first introduced by Amari in 1985, we see that the local state space is an Einstein space, and also a dually flat manifold with the Fisher metric; the differential operator of the Kolmogorov equation is the affine Laplacian which can be represented in various coordinates and on various spaces. Dynamics on the whole state space explains some biological phenomena.