Emerging infectious diseases can exert strong selection on hosts to evolve resistance or tolerance to infection. However, it remains unknown whether the evolution of specific defense strategies against a novel pathogen influences host immune phenotypes more broadly, potentially affecting their ability to respond to other pathogens. In 1994 the bacterial pathogen, Mycoplasma gallisepticum (MG) jumped from poultry into house finches, causing severe conjunctivitis and reducing host survival. MG then spread across the continental United States, exerting strong selection on host populations and creating geographic variation in the degree of population co-evolutionary history with the pathogen. Prior work found that populations of house finches with longer histories of MG endemism have evolved tolerance and resistance to MG, and this evolution is associated with several immunological differences including reductions in pro-inflammatory immune responses. However, it remains unknown whether these immunological changes are limited to MG-specific defenses or whether broader immune responses differ between populations with distinct coevolutionary histories with MG. To examine possible effects of the evolution of host responses to MG, we used five immune assays to challenge house finches from four populations, ranging from no history of MG endemism to 20+ years of MG endemism. When challenged with phytohemagglutinin (PHA), populations differed significantly in the strength of wing web swelling, with populations with longer MG exposure (and thus the highest MG tolerance) on average exhibiting the weakest swelling response when mass differences were controlled for. However, detected population differences in wing web swelling were small, and population differences were absent for responses to four other immune assays that spanned components of the innate and adaptive immune system. Future work should examine whether the local inflammation that underlies swelling responses to PHA shares common immunological mechanisms with local inflammatory responses to MG, which may explain why populations with evolved tolerance to MG show slightly lower swelling responses in response to PHA. Overall, these results suggest that the evolution of MG tolerance may have minor downstream consequences for responses to certain antigens, with the potential to influence a host's ability to respond to novel pathogen challenges, but most components of the host immune system appear largely unaffected. / Master of Science / Emerging infectious diseases can have devasting effects on new host species. To reduce the cost of these pathogens, host species can evolve ways to eliminate infection (resistance) or reduce damage during infection (tolerance), which is often caused by the host's immune system itself. As populations evolve these disease strategies, it is likely that other aspects of the immune system will also be affected, potentially compromising the ability of hosts to respond to pathogens other than the ones they evolved defenses against. We examined what sort of trade-offs might arise as house finches evolved resistance and tolerance to a new deadly pathogen, Mycoplasma gallisepticum (MG). House finch populations in the mid-Atlantic were first exposed to the disease in 1994, and as the disease spread across the continental United States, different populations have been exposed for different periods of time. This created a gradient in whether certain populations have had long enough time with MG to evolve disease strategies. Populations that have been exposed to MG for longer appear to have evolved both resistance and tolerance, and tolerant populations show lower levels of inflammatory immune markers that can be associated with self-damage. Using house finches from four different populations (ranging from 25 years of exposure history to zero years of MG exposure history), we tested a variety of immune system components to examine what areas of the immune system might have been broadly affected by the evolution of resistance and tolerance. We hypothesized that birds from populations with evolved MG tolerance would also have a reduced inflammation response when stimulated with substances that mimic infection by something other than MG. Only one assay supported this hypothesis. Birds from populations that had been exposed to MG for a longer period of time (and thus had evolved MG tolerance) had a reduced swelling response following injection with a plant protein called phytohemagglutinin. However, there were no population differences observed with the other four assays, suggesting that evolving defenses against MG did not result in widespread immunological effects. This suggests that the evolution of host defenses against an emerging pathogen may not compromise that host's ability to respond effectively to other types of pathogens that they encounter in nature.

Les mutations sont à l'origine des nombreux "variants" présents dans les populations naturelles. Les variants adaptatifs sont propagés par sélection naturelle. Cependant, une mutation bénéfique sur un trait peut affecter négativement d’autres traits (coût sélectif): un compromis émerge alors entre les avantages et les coûts qu’elle induit. Cette thèse vise à comprendre comment des modifications de l’environnement peuvent affecter les compromis évolutifs de différents types de mutations adaptatives (substitutions, duplications hétérogènes, amplifications). Chez les moustiques, l’utilisation d’insecticides organophosphorés (OPs) et carbamates (CXs) a sélectionné trois réponses adaptatives majeures : une amplification de gènes au locus Ester (codant pour des enzymes détoxicantes), une substitution au locus ace-1 (codant pour la cible des insecticides), et des duplications associant une copie sensible et une copie résistante du locus ace-1. Un premier axe de ma thèse a été de mieux comprendre le rôle de ces duplications hétérogènes (qui associent deux copies divergentes d’un même gène) dans l’adaptation. En caractérisant leurs compromis évolutifs nous avons montré qu'elles confèrent un phénotype proche de celui d’hétérozygotes standards. Toutefois, l’étude de leur distribution mondiale et des analyses en laboratoire ont révélé que ces duplications, avantageuses à l’état hétérozygote, sont majoritairement sublétales à l’état homozygote. Le second axe de cette thèse a été l’étude de l’influence des variations de pression de sélection sur la dynamique des allèles adaptatifs. Une étude d’évolution expérimentale a montré que des pressions de sélection intermédiaires pouvaient générer des situations de superdominance au locus ace-1, favorables à la sélection de duplications hétérogènes. Par ailleurs, l’analyse d’échantillons montpelliérains récoltés sur une trentaine d’années nous a permis de relier quantitativement les variations de la pression de sélection et les variations de la valeur sélective des différents allèles du locus Ester. Enfin, l’étude de trois zones géographiques (Mayotte, Martinique, et Montpellier) a permis de montrer que les différentes adaptations ne répondaient pas de la même façon à une modification environnementale majeure liée au retrait de la pression de sélection (interdiction des OPs et CXs en 2007) : alors que les allèles de résistance du locus ace-1 tendent à disparaitre, ceux du locus Ester se maintiennent en fréquence non négligeable dans les populations naturelles. / Mutations are the origin of the many "variants" present in natural populations. Adaptive variants are propagated by natural selection. However a mutation beneficial for a trait can negatively affect other traits (selective cost): a trade-off thus emerges between the benefits and the costs it induces. This PhD aimed at understanding how environmental changes could affect the evolutionary trade-offs of various types of adaptive mutations (substitutions, heterogeneous duplications, amplifications). In mosquitoes, organophosphate (OPs) and carbamates (CXs) insecticides usage has selected three major adaptive responses: gene amplifications at the Ester locus (encoding detoxifying enzymes), a substitution at the ace-1 locus (encoding the target of the insecticides), and gene duplications pairing susceptible and resistance ace-1 copies. The first axis of my PhD aimed at understanding the role of these heterogeneous duplications (combining two different copies of the same gene) in adaptation. Characterizing their evolutionary trade-offs, we showed that they confer a phenotype similar to standard heterozygotes. However, the study of their worldwide distribution and laboratory analyzes showed that these duplications, advantageous at the heterozygous state, are mostly sublethal when homozygous. The second axis of this PhD was the study of the impact of selection pressure variations on the dynamics of adaptive alleles. An experimental evolution study showed that intermediate selective pressures could generate overdominance situations at the ace-1 locus, promoting the selection of heterogeneous duplications. Furthermore, analyzing Montpellier samples collected over a 27 years period allowed us establishing the quantitative relationship between selective pressure variations and fitness variations for the different Ester resistance alleles. Finally, by studying three different geographical areas (Mayotte and Martinique islands and Montpellier) we showed that the various adaptations were not responding similarly to a major environmental change resulting from the selection pressure withdrawal (OPs and CXs were banned in 2007): while the ace-1 locus resistance alleles tended to disappear, those of the Ester locus remained at a significant frequency in natural populations.

Pour comprendre l'origine des variations d'histoire de vie des organismes, il fautétudier et mettre en évidence les stratégies d'histoire de vie et les processus évolutifsqui les gouvernent. Ce travail de thèse a pour objectif d'étudier les stratégiesd'histoire de vie et leur conditionnement par les caractéristiques individuellesen conditions naturelles. Les stratégies d'histoire de vie sont vues comme un agencementde normes de réactions et de compromis évolutifs. Cependant, l'étude desprocessus évolutifs en milieu naturel se heurte à des problèmes d'ordre méthodologique.En effet, le suivi exhaustif au cours du temps d'individus d'une populationest difficilement réalisable, voire impossible en conditions naturelles. Les méthodesde capture-marquage-recapture permettent une observation partielle des histoires devie et des traits d'histoire de vie. Ce travail se base sur l'idée que nos observationsne sont que la partie visible de processus sous-jacents qu'il est nécessaire de prendreen compte pour ne pas biaiser nos inférences statistiques. J'utilise la modélisation àstructure cachée pour 1) séparer le processus d'observation du processus dynamiqued'intérêt, 2) modéliser les histoires de vie complètes des individus, 3) intégrer dansun cadre unique et cohérent les décisions d'histoire de vie et les compromis évolutifset 4) représenter explicitement les mécanismes sous-jacents qui génèrent nos observations.Dans ce cadre, on peut alors intégrer les théories et concepts de la biologieévolutive dans l'analyse statistique des données d'observations. J'illustre ce travailpar l'étude du conditionnement des stratégies d'histoire de vie dans une populationnaturelle de saumon Atlantique sur le Scorff (Morbihan) à partir de données de CMR.Mes résultats mettent en évidence des décisions d'histoire de vie statut-dépendanteset des compromis évolutifs qui n'auraient pas pu être mis en évidence hors du cadrede modélisation proposé. / Understanding the origin of life history variations of organisms requires studying life historystrategies and evolutionary processes that drive them. This thesis aims at studying life historystrategies under natural conditions and how they are conditioned by individual characteristics.Life history strategies are seen as a combination of reaction norms and evolutionarytrade-offs. The study of evolutionary processes in the wild faces to methodological issues.Indeed, the exhaustive monitoring of individuals over time is often impossible in the wild.Capture-mark-recapture methods allow a partial observation of life histories and life historytraits. This work was based on the idea that our observations are only the visible part ofunderlying processes that need to be accounted for to limit the risk of flawed statistical inferences.I resort to hidden structure modeling to 1) separate the observation process fromthe dynamic process of interest, 2) model the full life histories of individuals, 3) integratewithin a single and coherent framework life history decisions and evolutionary trade-offs and4) explicitly represent the underlying mechanisms that generate our observations. Withinthis framework, one can confront theories and concepts in evolutionary biology with observationaldata through appropriate statistical tools. Finally, I illustrate this work by studying theconditioning of life-history strategies in a natural population of Atlantic salmon on the Scorffriver (Morbihan) using CMR data. My results highlight status-dependent life history decisionsand evolutionary trade-offs that could not be identified without our proposed modelingframework.

Les théories évolutives du vieillissement et la théorie du «disposable soma» en particulier ont été la base théorique d'une avance récente de recherche sur le vieillissement animal. Pourtant, leur hypothèse centrale sur la physiologie de l'entretien et de la réparation cellulaires n'a pas été testée empiriquement. Dans cette thèse, j'ai analysé la physiologie du vieillissement de Escherichia coli sous restriction de carbone, en tant que système modèle pour valider empiriquement les théories évolutives du vieillissement. Les outils microfluidiques sont utilisés pour isoler de larges populations de cellules isolées de E. coli et pour obtenir une restriction carbonée homogène. Malgré le partage de la même génétique et des conditions environnementales, les cellules individuelles de la population présentent des variations significatives de la durée de vie et de cause de décès. Les distributions de durée de vie présentent des caractéristiques typiques du processus de vieillissement, souvent observées en études démographiques animales et humaines. Le taux de vieillissement peut être modifié par des mutations de la réponse générale au stress. Comme la longévité induite par la restriction calorique, la réponse générale au stress prolonge la durée de vie d'E.coli en atténuant l'effet du vieillissement au détriment des besoins immédiats des cellules. Un modèle quantitatif de ce compromis physiologique est construit et correctement prédit des observations expérimentales. En conclusion, je confirme la théorie du «disposable soma» du vieillissement avec les détails physiologiques du vieillissement de E.coli en famine. / The evolutionary theories of aging and the disposable soma theory in particular, have been the theoretical basis for a recent surge of animal aging research. Yet their central assumption about the physiology of cellular maintenance and repair has not been empirically tested. In this thesis, I analysed the physiology of E.coli aging under carbon starvation, as a model system to empirically validate evolutionary theories of aging. Microfluidic tools are used to isolate large populations of isogenic single E.coli cells, and to achieve homogenous carbon starvation. Despite sharing the same genetical background and environmental conditions, individual cells in the population exhibit significant variations in lifespans and causes of death. Distributions of lifespans exhibit typical features of the aging process, often seen in animal and human demographic studies. The rate of aging can be altered by mutations of the general stress response pathway. Resembling caloric restriction induced longevity, the general stress response pathway extends starvation lifespans of E.coli by attenuating the effect of aging at the expense of immediate needs of the cells. A quantitative model of this physiological trade-off is constructed and correctly predicted experimental observations. As a conclusion, I substantiate the disposable soma theory of aging with the physiological details of E.coli aging in starvation.