La canalisation génétique est définie comme la capacité d’un organisme à avoir un développement constant en dépit des mutations qui l’affectent. A l’heure actuelle, trois hypothèses majoritaires cherchent à expliquer l’apparition de ce processus : évolutive, congruente et intrinsèque. Pour tester ces hypothèses, j’ai choisi d’étudier les réseaux de régulation. Pour cela, j’ai réutilisé un modèle théorique pour simuler in silico l’évolution des architectures génétiques, et les analyser par les outils de la génétique quantitative. J’ai d’abord étudié les comportements évolutifs de notre modèle et sa capacité de réponse à la sélection stabilisante. Outre l’analyse de l’impact des paramètres du modèle, j’ai mis en évidence l’absence d’équilibre mutation – sélection – dérive après des milliers de générations du fait de l’augmentation progressive de la canalisation. J’ai ensuite montré que les réseaux soumis à des mutations fréquentes et fortes, sélectionnés vers des optimums phénotypiques extrêmes, et dans lesquels certains gènes sont laissés libres d’évoluer sont plus aptes à faire évoluer de la canalisation génétique. Ces résultats nous ont amenés à proposer un double mécanisme impliqué dans l’évolution de la canalisation dans les réseaux de régulation : la réduction de la cible mutationnelle et la redondance de la régulation génique. Je termine ce manuscrit en présentant quelques pistes d’études complémentaires, portant notamment sur l’étude de la canalisation contre les perturbations environnementales et l’utilisation de modèles alternatifs. / Genetic canalization is defined as the capacity of an organism to undergo a normal development even when the genome is altered by mutations. Currently, three main hypotheses are prone to explain the apparition of such a process: evolutionary, congruent and intrinsic. To test these hypotheses, I chose to study gene regulatory networks. To this end, I used a theoretical model, ran in silico simulations, and analyzed the genetic architecture by using quantitative genetics tools. I first studied the evolutionary behavior of the model, and its capacity to respond to stabilizing selection. In addition to the sensitivity analysis to model parameters, I evidenced the absence of mutation-selection-drift equilibrium after several thousand generations, which reveals the evolution of canalization. I also showed that networks submitted to frequent and large mutations, and/or selected toward extreme phenotypic optima are more prone to evolve genetic canalization. This result leads us to propose a two-fold mechanism able to explain the evolution of canalization in gene regulatory networks: shrinkage of mutational targets and redundancy in genetic regulation. At the end of this manuscript, I propose some possible future studies, such as the study of canalization towards environmental perturbations, and use of alternative models.

abstract: Bioarchaeologists often use dental data and spatial analysis of cemeteries to infer the biological and social structure of ancient communities. This approach is commonly referred to as biological distance (“biodistance”) analysis. While permanent crown data feature prominently in these efforts, few studies have verified the accuracy of biodistance methods for recognizing child relatives using deciduous teeth. Thus, as subadults comprise an essential demographic subset of mortuary assemblages, deciduous phenotypes may represent a critical but underutilized source of information on the underlying genetic structure of past populations. The goal of the dissertation is to​ quantitatively analyze the developmental program underlying deciduous phenotypes and​ to evaluate their performance in accurately reconstructing known genealogical relationships.​ This project quantifies morphological variation of deciduous and permanent tooth crowns from stone dental casts representing individuals of known pedigree deriving from three distinct populations: European Canadians, European Australians, and Aboriginal Australians. To address the paucity of deciduous-focused validation research, phenotypic distances generated from the dental data are subjected to performance analyses (biodistance simulations) and compared to genetic distances between individuals. While family-specific results vary, crown morphology performs moderately well in distinguishing relatives from non-relatives. Comparisons between deciduous and permanent results (i.e., Euclidean distances, Mantel tests, multidimensional scaling output) indicate that deciduous crown variation provides a more direct reflection of the underlying genetic structure of pedigreed samples. The morphology data are then analyzed within a quantitative genetic framework using maximum likelihood variance components analysis. Novel narrow-sense heritability and pleiotropy estimates are generated for the complete suite of deciduous and permanent crown characters, which facilitates comparisons between samples, traits, dentitions, arcades, antimeres, metameres, scoring standards, and dichotomization breakpoints. Results indicate wide-ranging but moderate heritability estimates for morphological traits, as well as low to moderate integration for characters within (deciduous-deciduous; permanent-permanent) and between (deciduous-permanent) dentitions. On average, deciduous and permanent homologues are more strongly genetically correlated than characters within the same tooth row. Results are interpreted with respect to dental development and biodistance methodology. Ultimately, the dissertation empirically validates the use of dental morphology as a proxy for underlying genetic information, including deciduous characters. / Dissertation/Thesis / Doctoral Dissertation Anthropology 2017

No description available.

Phenotypic plasticity is the ability of the genotype to express alternative phenotypes in response to different environmental conditions and this is considered to be an adaptation in which a species can survive and persist in a rapidly changing environment. Some grasshoppers and locusts are capable of expressing an extreme form of density-dependent phenotypic plasticity, known as locust phase polyphenism. At low population density, the individuals typically have a cryptic coloration as nymphs, are less active, and only seek out conspecifics for reproductive purposes. At high density, however, they develop a drastically different phenotype in which they have a conspicuous coloration, are much more active, and tend to stay together in large groups. The American Birdwing grasshopper, Schistocerca americana, is a non-swarming species related to the desert locust, S. gregaria, which shows density-dependent phenotypic plasticity in behavior, color, and morphology. In this thesis, I have identified the duration of crowding necessary for a 6th instar S. americana reared in the isolated condition to express the typical crowded behavior. The behavior changed after just one hour of crowding and the effect of crowding diminished after 48 hours to near-complete isolated behavior. In reverse, the crowded condition was isolated, but behavior did not significantly change over time. Gene expression of the following three genes suspected of having a role in behavior change were investigated based on studies of S. gregaria: protein kinase A (PKA), L-Tryptophan-5-monooxygenase (T-5), and Aromatic L-amino acid decarboxylase (Decarb). T-5 was up-regulated in the long-term isolated condition compared to the long-term crowded condition. T-5 and Decarb were up-regulated in isolated individuals that were crowded for 10 hours compared to the long-term isolated condition. This study represents a novel contribution in the study of phenotypic plasticity as it establishes the time course of behavioral and molecular plasticity in a non-swarming grasshopper for the first time.

<p> Fruit size is a polygenic trait controlled by multiple genomic regions each with small effect. The complex nature of fruit size regulation makes it challenging to dissect individual genes responsible for phenotypic variation. Though recent advances in high-throughput genome sequencing technology in conjunction with improved statistical and computational methods empowered science to explicitly understand the genetic basis underlying multiple fruit quality traits, much of the work that has been done through classical quantitative trait loci (QTL) approach resulted in reduced resolution and instability when evaluating in different genetic backgrounds and different environments. To increase the precision and improve the stability of QTL analyses and to identify genes controlling fruit size, we performed a set of multiple quantitative and molecular genetic analyses to elucidate the underlying genetic architecture of fruit mass. A total of nine genomic regions associated with fruit mass were identified, two of which are novel to this study; markers Md14_26050918 and Md14_26050904. Detected QTLs explained ~ 42% of the total genetic variation of which ~ 20% is explained by the two novel QTLs. Regions responsible for fruit mass variation appear to be under strong additive and epistatic genetic control. These regions exhibited high stability across-family as well as across-years and showed accurate genomic prediction across-family. Additionally, we identified the apple gene family of putative fw2.2 orthologs, naming them Cell Number Regulators (CNRs) genes (MdCNRs). Three CNRs (MdCNR1-3) showed increased expression at early fruit growth in small-fruited crabapple, associating with reduced relative cell production rate (RCPR), suggesting that alteration in cell number that leads to a subsequent reduction in fruit size is probably due to reduced cell division most likely due to changes in CNRs regulation. Furthermore, our study revealed that reduced fruit size is partially due to the shortened cell expansion period after which cell expansion ceases in the small-fruited crabapple species. Together, these data will advance our understanding of dissecting fruit mass genetic architecture and have high potential to be deployed for marker-assisted selection and further breeding approaches. </p>

<p dir="ltr">Metabolic pathways are shaped by dynamic biotic interactions. My research delves into coevolution exemplified through two distinct projects that investigate the specialized metabolism of organisms as a consequence of biotic interactions. The first project focused on the remarkable metabolic adaptations of <i>Elysia crispata</i> morphotype clarki. This sea slug possesses the extraordinary ability to sequester and maintain functional chloroplasts (kleptoplasts) from the algae it consumes, allowing it to sustain photosynthetically active kleptoplasts for several months without feeding. To better understand the underlying molecular mechanism of this phenomenon, I generated a comprehensive 786 Mbp draft genome of <i>E. crispata</i> using a combination of ONT long reads and Illumina short reads. The resulting assembly provided a foundational resource for phylogenetic, gene family and gene expression analyses. This work advanced our understanding of the genetic underpinnings of kleptoplasty, shedding light on the evolution and maintenance of this unique metabolic strategy in sacoglossan sea slugs. I next investigated the transcriptional impacts of herbivory on maize (<i>Zea mays</i>) and green foxtail (<i>Setaria viridis</i>), induced by fall armyworm (<i>Spodoptera frugiperda</i>) and beet armyworm (<i>Spodoptera exigua</i>) feeding. This study aimed to contrast the defensive mechanisms of these grasses in response to each herbivore, and determined that green foxtail transcriptionally differentiates its responses to fall armyworm and beet armyworm herbivory. The fall armyworm has evolved a counter adaptation to lessen plant secondary metabolite production by producing a salivary protein (SFRP1) that suppresses jasmonate signaling. Investigation of the combinatorial effects of SFRP1 and beet armyworm herbivory determined the addition of endogenous SFRP1 during beet armyworm feeding is sufficient to reduce green foxtail defense responses. Results of this research shed light on host-pest reciprocal adaptations and the role of SFRP1 as an oral secretory protein. Coexpression analysis of maize and green foxtail transcriptomic responses to herbivory also identified putative genes involved in specialized metabolic pathways in green foxtail, providing insights into plant-insect interactions and potential solutions to herbivory in wild plant species. These findings highlight how gene diversification can contribute to pest resistance in grasses. Together, these seemingly unconnected projects underscore how biotic interactions influence metabolic processes across diverse organisms and reveal the fascinating intricacies of their adaptations to environmental challenges.</p>

<p dir="ltr">In this dissertation, we investigated the genetic background of milk consumption, feeding behavior, disease resistance, and calf resilience in North American Holstein dairy calves using precision livestock farming (PLF) technologies and genetic modeling. Genomic and phenotypic information obtained from automatic milk feeding machines were obtained from 10,072 pre-weaned Holstein calves and used to derive and genetically evaluate novel traits such as daily milk consumption, calf resilience, and incidence of bovine respiratory disease (BRD). Heritability estimates for milk consumption and feeding behavior traits were found to be low but improved with specific statistical models, suggesting potential for genetic improvement if included in selection schemes. Random regression models captured greater amounts of genetic variability among calves for longitudinal milk feeding and behavior traits, with moderate negative (favorable) genetic correlations between milk consumption and BRD, indicating potential for genetic selection to enhance calf health outcomes and performance based on milk intake data. Various quantitative trait loci (QTL) for milk consumption, drinking duration traits, feeding behavior, and disease susceptibility were identified, linking key genes involved in metabolic processes, growth, and overall health. The same datasets were used to derive resilience indicators based on cumulative milk consumption. Genetic parameters for resilience traits, including amplitude, perturbation time, and recovery time, were estimated, highlighting substantial phenotypic and genetic variability. Significant genomic regions for six resilience traits were identified, with key genes such as <i>ABCB8</i>,<i> ABCF2</i>, and <i>AGAP3</i> linked to resilience traits, impacting mitochondrial function, cellular stress responses, and homeostasis. Pathway analyses revealed critical biological processes for stress response, including nucleotide binding and hormone activity. Genes such as <i>EPC1</i>, <i>ASB10</i>, and <i>ASIC3</i> were associated with recovery time, while <i>DPP6</i>, <i>GBX1</i>, and <i>GIMAP5</i> were linked to other resilience traits. These findings underscore the importance of genetic tools and breeding strategies in enhancing health, resilience, and productivity, offering potential new traits to genetically improve health and resilience in dairy cattle, and consequently, improve the sustainability of the dairy cattle industry.</p>

Understanding the causes of individual differences in brain structure may give clues about the etiology of cognition, personality, and psychopathology, and also may identify endophenotypes for molecular genetic studies on brain development. We performed a comprehensive statistical genetic study of anatomic neuroimaging data from a large pediatric sample (N=600+) of twins and family members from the Child Psychiatry Branch at the NIMH. These analyses included variance decomposition of structural volumetric endophenotypes at several levels of resolution, voxel-level analysis of cortical thickness, assessment of gene by age interaction, several multivariate genetic analyses, and a search for genetically-mediated brain-behavioral relationships. These analyses found strong evidence for a genetic role in the generation of individual differences in brain volumes, with the exception of the cerebellum and the lateral ventricles. Subsequent multivariate analyses demonstrated that most of the genetic variance in large volumes shares a common source. More subtle analyses suggest that although this global genetic factor is the principal determinant of neuroanatomic variability, genetic factors also mediate regional variability in cortical thickness and are different for gray and white matter volumes. Models using graph theory show that brain structure follows small-world architectural rules, and that these relationships are genetically-determined. Structural homologues appeared to be strongly related genetically, which was further confirmed using novel methods for semi-multivariate quantitative genetic analysis at the voxel level. Studies on interactions with age were mixed. We found evidence of gene by age interaction on frontal and temporal lobar volumes, indicating that the role of genetic factors on these structures is dynamic during childhood. Analyses on cortical thickness at a finer scale, however, showed that environmental factors are more important in childhood, and environmental changes were responsible for most of the changes in heritability over this age range. When assessing the relationship between brain and behavior, we found weak negative genetic correlations and positive environmental correlations between IQ and cortical thickness, which appear to partially cancel each other out. More complex models allowing for age interactions suggest that high and low IQ groups have different patterns of gene by age interactions in concordance with prior literature on cortical phenotypes.

Comprendre quels mécanismes contrôlent la variabilité phénotypique et comment ces mécanismes influencent et contraignent la divergence interspécifique est un objectif important en biologie de l'Evolution. Dans cette thèse, nous avons essayé d'étudier comment l'histoire phylogénétique, la génétique, l'environnement, et le développement influencent l'évolution d'une structure morphologique complexe, en utilisant la mandibule de la souris domestique comme modèle.Afin d'étudier les processus qui contrôlent la variation phénotypique, des analyses de génétique quantitative ont été réalisées sur un pedigree obtenu à partir des individus sauvages d'une population de la souris domestique. Les descendants ont été divisés en deux, l'un suit un régime alimentaire dur et l'autre un régime alimentaire mou, pour que l'effet de la plasticité phénotypique puisse être considérée. On montre que le développement et les contraintes épigénétiques pourraient changer l'architecture génétique des traits morphologiques dans une population. En outre, les résultats suggèrent que la plasticité phénotypique pourrait être adaptative dans certaines conditions environnementales, mais pas dans d'autres.Ensuite, on a utilisé la mandibule de la souris domestique pour étudier les patrons de l'évolution morphologique des populations de cette espèce dans un contexte phylogéographique. Les résultats suggèrent que la divergence morphologique chez la souris domestique a suivi la différenciation génétique. On a aussi trouvé que la variation morphologique a augmenté au cours de l'expansion des sous-espèces sans qu'une convergence significative n'accompagne l'évolution vers le commensalisme avec l'homme. Finalement on a déterminé si l'hypothèse d'évolution de la mandibule sous l'effet de la dérive génétique peut expliquer la diversification morphologique au cours de la divergence et d'expansion de la souris domestique. Les résultats rejettent cette hypothèse et plaident en faveur d'autres forces évolutives telles que la sélection.Nos résultats, dans leur ensemble, montre une origine multifactorielle de la variation et permettent de mieux comprendre la diversification morphologique des populations et des sous-espèces de la souris domestique. / A major goal of evolutionary biology is to understand which mechanisms monitor phenotypic variation and how this variation can generate species diversity. In this thesis we tried to investigate how phylogenetic, genetic, environmental, and development influence the evolution of a complex morphological structure using house mouse mandible as a model.In order to study the processes monitoring phenotypic variation, quantitative genetic analyses were performed on a pedigree of wild captured specimens of house mouse. The progenies were divided into two groups followed two different diets (soft and hard), so that the effect of phenotypic plasticity can be regarded. We show that developmental and epigenetic factors could influence the genetic architecture of morphological traits in a population. Moreover, the results suggest that phenotypic plasticity might be adaptive in some environmental conditions but not in the others.We then used the house mouse mandible in order to study the patterns of morphologic evolution of the populations of this species in a phylogeographic context. Our results show that morphological divergence in the house mouse was followed the genetic differentiation. We also found that morphological variation was increased during the expansion of house mouse subspecies without a significant convergence due to commensalism with human. Finally, we investigated whether the hypothesis of genetic drift could explain the morphological diversification during the divergence and expansion of the house mouse. The results reject this hypothesis and argue for the interfering of other evolutionary forces like selection.Our results, all in all, show a multifactorial origin for phenotypic variation and permit us to better understand the morphological divergence of the population of the subspecies of house mouse.

L'alternance de production est définie comme la charge en fruit d'un arbre irrégulière sur plusieurs années consécutives. La principale hypothèse en soulignant l'alternance est que la charge en fruits d'une année en cours inhibe la formation de fleurs pour l'année suivante. Ce phénomène génère d'importants problèmes agronomiques pour les espèces fruitières comme le pommier, en réduisant la production de fruits au cours des années 'OFF' et la qualité des fruits au cours des années 'ON', tout en augmentant les coûts de gestion des vergers, en particulier pour l'éclaircissage des fruits. Une stratégie pour atténuer l'alternance est de développer de nouvelles variétés avec une production régulière. Les principaux objectifs de ma thèse étaient: (i) d'améliorer les stratégies de phénotypage et les méthodes pour caractériser l'alternance de production, (ii) de disséquer le contrôle génétique de l'alternance de production en utilisant une descendance de pommier en ségrégation et d'identifier les principales régions génétiques responsables de la variation du caractère, et (iii) d'étudier les processus physiologiques sous-jacents à l'alternance de production. J'ai combiné des méthodes comme la modélisation, la génétique quantitative, la détection de Quantitative Trait Loci (QTL) et de gènes candidats ainsi que la cartographie et l'expression de gènes.Mon étude a utilisé une population de pommier ségrégation obtenue à partir d'un croisement entre des parents contrastés pour les caractéristiques architecturales et de floraison (‘Starkrimson' x 'Granny Smith'). Le phénotypage de la population pour l'alternance de production a été réalisée à l'échelle d'arbres entiers, en observant les occurrences de floraison pendant six années consécutives, et à l'échelle locale, en observant la succession de méristèmes floraux vs végétative en position terminale de rameaux. De ces données, de nouveaux modèles ont été développés afin de quantifier l'alternance de la production, en tenant compte de la croissance ontogénétique de la production et la présence / absence de floraison entre les années successives le long des pousses courtes. Ceci nous a conduits à proposer de nouveaux descripteurs de la tendance d'un génotype à l'alternance de production dans les premiers stades de développement des arbres et ouvre des possibilités pour une évaluation plus rapide et plus précoce de ce caractère dans les programmes de sélection de fruits à pépins.Pour identifier les régions génomiques impliquées dans l'alternance, une détection de QTL a été réalisée sur la base des données phénotypiques et des valeurs de BLUP obtenues à partir des modèles. J'ai démontré que la régularité de la production est sous contrôle polygénique. J'ai extrait une liste de gènes qui sont présents au sein de ces QTL en utilisant la séquence du génome du pommier. Les principaux gènes candidats identifiés sont liés aux gibbérellines, aux auxines, et à la floraison. J'ai étudié l'expression des gènes candidats co-localisant avec des QTLs par PCR quantitative en utilisant les méristèmes prélevés sur les arbres portant une forte charge en fruits vs une faible charge. Une analyse microarray m'a permis d'obtenir un aperçu global des processus biologiques et de l'expression des gènes qui sont modulés dans le méristème lorsque des fruits sont présents. Certains gènes liés à la floraison, au développement du méristème, aux gibbérellines et aux auxines ont montré un profil d'expression affectée par la présence de fruits.Mes résultats fournissent des éclaircissements sur le contrôle physiologique et génétique de ce caractère complexe qui est l'alternance et ouvrent la perspective d'inclure la régularité de production dans les schémas de sélection de pommier et d'autres espèces fruitières / Biennial bearing is defined as the irregular crop load of a tree over consecutive years. The main assumption underlining biennial bearing is that the fruit load of a given year inhibits flower formation for the following year. This phenomenon generates major agronomic problems for fruit species such as apple, by reducing fruit production during ‘OFF' years and fruit quality during ‘ON' years, while increasing orchard management costs, especially for fruit thinning. A strategy to attenuate biennial bearing is to develop new varieties with regular production. The main objectives of my project were (i) to improve phenotyping strategy and methodology for biennial bearing characterisation, (ii) to dissect the genetic control of biennial bearing using an apple segregating progeny and to identify key genetic regions responsible for the trait variation, and (iii) to investigate physiological processes underlying biennial bearing. I combined methodologies such as modelling, quantitative genetics, candidate gene and Quantitative Trait Loci (QTL) mapping and gene expression.My study used an apple segregating population issued from a cross between contrasting parents for architectural and flowering features (‘Starkrimson' x ‘Granny Smith'). Phenotyping of the population for biennial bearing was achieved at whole tree scale by observing flowering occurrence for six consecutive years, and at local scale, by observing the succession of floral vs. vegetative meristems in terminal position of shoots. From this data, new models were constructed to quantify the alternation of production, taking into account the ontogenetic increasing trend of production and the presence/absence of flowering between successive years along short shoots. This led us to propose new descriptors of the tendency of a genotype to biennial bearing in the early stages of tree development and opens possibilities for a faster and earlier evaluation of this character in pipfruit breeding programmes and for orchard management.To identify genomic regions involved in biennial bearing, a QTL detection was performed on the basis of phenotypic data and BLUP values obtained from the models. I demonstrated that the regularity of production is under polygenic control. I mined a list of genes that are present within these QTLs using the apple genome sequence. The main candidate genes identified are related to gibberellins, auxins, and flowering.I investigated the expression of candidate genes co-locating with QTLs by quantitative PCR using meristems collected on trees bearing heavy fruit load vs. light crop. A microarray analysis enabled me to obtain a global overview of biological processes and gene expression that are modulated in the meristem when fruits are present. Some genes related to flowering, meristem development, gibberellins and auxins showed an expression profile affected by the presence of fruit.My results provide elucidation on the physiological and genetic control of the complex trait that is biennial bearing and open up the perspective of including regular bearing in breeding schemes for apple and other fruit species.