Evolutionary dynamics arise from the interplay of mutation and selection. Fundamentally, these two processes operate at different levels: Mutations modify genetic information (the genotype), which is passed from parent to offspring. Selection is triggered by variation in reproductive success, which depends on the physical properties (the phenotype) of an organism and its environment. Thus the genotype-phenotype map determines if and how mutations can lead to selection. The aim of this dissertation is to incorporate this map explicitly into a theoretical description of evolutionary dynamics. The first part of the analysis presented here is concerned with the static properties of simple models of these maps, which are studied using exhaustive enumeration. The two most important observations are phenotypic bias – some phenotypes are realized by many more genotypes than most other phenotypes – and the existence of neutral spaces – genotypes with the same phenotype can often be reached from each other by single mutational steps. The remainder of the dissertation provides a theoretical description of evolutionary dynamics on and across neutral spaces. Two different mean-field approximations lead to simple analytic results for the first discovery of alternative phenotypes, highlighting the importance of phenotypic bias: Rare phenotypes are hard to find by evolutionary search. These results are used to discuss the relationship of robustness, the ability to withstand mutational change, and evolvability, the ability to create variation through mutation. Several types of fluctuations beyond the mean-field limit are studied, both theoretically and in simulations. The discrete structure of genotype spaces can lead to strong correlations in the spectra of phenotypes produced, increasing the probability that a particular phenotype is fixed in the population quickly after its discovery. Structural correlations between genotypes can increase the effect of phenotypic bias, while the qualitative features of the mean-field description remain valid. All these results highlight that neutral spaces impact evolutionary dynamics in many non-trivial ways, in particular by favouring phenotypes of high accessibly, but comparably low fitness over those phenotypes that are highly fit, but very hard to discover.

Genotype microarrays assay hundreds of thousands of genetic variants on an individual's genome. The availability of this high throughput genotyping capability has transformed the field of genetics over the past decade by enabling thousands of individuals to be rapidly assayed. This has lead to the discovery of hundreds of genetic variants that are associated with disease and other phenotypes in genome wide association studies (GWAS). These data have also brought with them a number of new statistical and computational challenges. This thesis deals with two primary analysis problems involving microarray data; genotype calling and haplotype inference. Genotype calling involves converting the noisy bivariate fluorescent signals generated by microarray data into genotype values for each genetic variant and individual. Poor quality genotype calling can lead to false positives and loss of power in GWAS so this is an important task. We introduce a new genotype calling method that is highly accurate and has the novel capability of fusing microarray data with next-generation sequencing data for greater accuracy and fewer missing values. Our new method compares favourably to other available genotype calling software. Haplotype inference (or phasing) involves deconvolving these genotypes into the two inherited parental chromosomes for an individual. The development of phasing methods has been a fertile field for statistical genetics research for well over ten years. Depending on the demography of a cohort, different phasing methods may be more appropriate than others. We review the popular offerings and introduce a new approach to try and unify two distinct problems; the phasing of extended pedigrees and the phasing of unrelated individuals. We conduct an extensive comparison of phasing methods on real and simulated data. Finally we demonstrate some preliminary results on extending methodology to sample sizes in the tens of thousands.

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Les apports de l’aquaculture représentent aujourd’hui la moitié des produits aquatiques destinés à la consommation humaine. La composition de l’aliment artificiel utilisé en élevage piscicole a fortement évolué ces 30 dernières années. Les produits d’origine végétale terrestre y ont progressivement remplacé les farines et les huiles de poisson lorsque les stocks de pêche minotière utilisés pour leur production se sont rapprochés de leur limite d’exploitation. Toutefois, l’usage exclusif de ces farines et huiles végétales conduit encore à la dégradation de la croissance et de la santé des salmonidés et des poissons marins. Dans le même temps, l’amélioration génétique en pisciculture a permis, depuis 1980, des gains importants sur les caractères de croissance, de santé et de qualité et dispose aujourd’hui de méthodes pour étudier les conséquences de cette profonde transition alimentaire sur les populations actuelles et futures issues des programmes de sélection. En privilégiant la comparaison entre un aliment composé de produits d’origine marine (M) et un aliment entièrement constitué de produits d’origine végétale terrestre (PB), nous avons étudié les voies d’amélioration génétique chez deux espèces majeures du secteur français : le bar européen (Dicentrarchus labrax) et la truite arc-en-ciel (Oncorhynchus mykiss). Dans ce contexte, l’objectif était en particulier d’estimer les héritabilités des caractères d’intérêt et l’importance des interactions génotype-aliment, qui sont à l’origine de reclassement des génotypes en fonction l’aliment utilisé.Les essais réalisés ont confirmés l’effet de la substitution totale sur la croissance et la composition lipidique chez les deux espèces et sur la survie chez le bar. Les héritabilités estimées des poissons nourris avec l’aliment PB pour le poids, la croissance et les paramètres de transformation technologique (rendement carcasse, viscères, tête, filet) sont hautes chez la truite (respectivement 0,69 ; 0,65 ; 0,21-0,58) et modérées chez le bar (respectivement 0,18 et 0,11). Pour ces caractères, les interactions génotype-aliment sont modérées et les corrélations génétiques estimées entre les aliments M et PB sont élevées chez la truite (respectivement 0,90 ; 0,92 ; 0,65-0,96) et chez le bar (respectivement 0,96 ; 0,64). Les gains génétique attendus sont plus élevés avec l’aliment PB qu’avec l’aliment M chez la truite tandis qu’ils sont plus faible chez le bar. La mesure de la réponse à la sélection pour une aptitude à grandir et à survivre en utilisant l’aliment PB a confirmé des gains élevés pour le poids (+35%), la survie (+15,1%) et la biomasse produite (+54,4%) sans impact sur les paramètres de transformation technologique (carcasse, viscères, tête, filet). Les essais réalisés ont confirmé que cette meilleure aptitude était liée à des modifications de l’activité du métabolisme lipidique mais n’ont pas permis de conclure à des liens avec l’ingéré et efficacité alimentaire.Les plus fortes mortalités et le plus faible poids des lots PB durant les jours qui suivent les premières prises alimentaires ainsi que les reclassements familiaux plus importants en début de cycle de vie indiquent que les stades précoces ont une place prépondérante dans l’utilisation de l’aliment d’origine végétale aux niveaux phénotypique et génétique et devront être approfondis.A la vue des résultats obtenus, il semble donc possible d’exploiter la grande plasticité de certaines espèces de poissons pour concevoir des programmes de sélection prenant en compte l’évolution des environnements de production. La limitation mondiale des ressources alimentaire confronte les élevages à des modifications rapides de l’aliment et l’amélioration génétique des cheptels peut aider à faciliter ces transitions alimentaires. / Nowadays, aquaculture contributes to half of the aquatic products intended for human consumption. The composition of aquafeeds strongly evolved in the past 30 years. Terrestrial plant-based products gradually replace fish meal and fish oil, as fish stocks used for their production reach their exploitation limit. However, the use of diets containing vegetable oils and meals only still lead to growth and health degradation in salmonids and marine fish.Besides, breeding programmes in fish farming allowed strong genetic progress, since 1980, on growth, health and quality traits. An important issue for fish breeders is now to understand the consequences of this deep dietary change on the current and future selected populations and to adapt breeding programs accordingly.Focusing on the comparison between two experimental diets, a diet containing marine products (M) and a diet containing only plant-based products, (PB), we investigated the possible impact of the dietary changes on the organization and the objectives of breeding programs in two major species of the French sector: the European sea bass (Dicentrarchus labrax) and the rainbow trout (Oncorhynchus mykiss). A key objective was to estimate the heritabilities of the main traits of economic interest and the importance of genotype by diet interactions, which may cause genotypes rerankings according to diet used. We also sought the potential origin of the variability for ability to use the PB diet and proposed scenarii for evolution of breeding programs.The trials confirmed that substitution of marine ingredients by vegetal ones decreased growth and lipid composition in both species, as well as survival in sea bass and, to a lesser extent in rainbow trout. The estimates of heritabilities for weight, growth and processing traits (carcass viscera, head and filet yields only measured on trout) when fish were fed with the PB diet were high in rainbow trout (respectively 0.69; 0.65; 0.21-0.58) and weak in sea bass (respectively 0.18 and 0.11). In trout and sea bass, these estimates were respectively higher and lower than those obtained when fish were fed the M diet. For these traits, genotype by diet interactions were moderate and the genetic correlations between the M and PB diets were variable in trout (respectively 0.67-0.90; 0.92; 0.65-0.96) and sea bass (respectively 0.51-0.96; 0.64) but could involve important family rerankings according to the period of survey. According to heritability estimates, expected genetic gains would be higher in trout for fish fed the PB diet than for fish fed the M diet when they would be weaker in sea bass. In trout, the measurement of the response to one generation of selection for the ability to grow and survive when fed the PB diet confirmed the results, and provided high genetic gains for body weight (+35%), survival rate (+15,1%) and produced biomass (+ 54,4%) without any impact on the processing traits (carcass, viscera, head, filet). We showed that this ability was associated to modifications in the lipid metabolism activities but could not establish links with feed intake or feed efficiency from our trials. Higher mortality rate and lower body weight in the PB batches during the first days following distribution of PB diet as well as stronger family rerankings in early steps of the survey indicate than the early stages play a key role in the use of plant-based diet at both phenotypic and genetic levels. Further insights dedicated to these particular stages are strongly needed.Based on present results, it seems possible to exploit the great plasticity of some fish species to conceive breeding programs taking into account a changing dietary environment. Facing the world limitation in food resources, genetic improvement of fish livestock can be a useful lever to facilitate dietary transitions.

Master of Science / Division of Biology / Michael A. Herman / Caenorhabditis elegans are free-living bacterivorous nematodes that naturally consume bacteria as food source. As an excellent genetic model, C. elegans has proven to be a successful system to study innate immune responses to human pathogens, which resulted in identification of many evolutionarily conserved defense pathways. Most of these studies examined innate immune pathway mutants in a single genetic background in response to monoculture of human pathogens that worms might not necessarily encounter in the wild. While this has led to the successful genetic dissection of these defense pathways, in order to fully understand their biological functions, the relevant ecological and evolutionary context needs to be taken into account. The bacterial environment C. elegans naturally encounter is likely to be highly heterogeneous. While many bacteria are mainly considered as dietary resource for worms, some could be potential pathogens. Worms thus constantly face the challenge to defend against the pathogens mixed in the food. Stenotrophomonas maltophilia is one such bacterium. S. maltophilia is a ubiquitous bacterium that has been found associated with native nematodes. But it can also cause nosocomial infections in human, especially in immune-compromised individuals. Due to its natural resistance to multiple antibiotics, it has been emerging as an opportunistic human pathogen. Our lab isolated a S. maltophilia strain, JCMS, which was found being pathogenic to C. elegans. Both C. elegans strains, N2 (Bristol, England) and CB4856 (Hawaii), showed decreased survivorship when fed on S. maltophilia JCMS compared to E. coli OP50. However, more interestingly, the specific responses towards bacteria are different between strains. This indicates that survivorship of C. elegans is determined by not only genetic and environmental factors, but also genotype by environment (G×E) interactions (GEI). In order to identify the underlying genetic basis, we mapped quantitative trait loci (QTL) in a N2×CB4856 recombinant inbred panel for the survivorship in response to E. coli OP50 and S. maltophilia JCMS.

Children who are more fearful and inhibited during early childhood are at greater risk for social problems (e.g., loneliness, social isolation) and clinically significant internalizing disorders during adolescence and adulthood (e.g., Rubin, Chen, McDougall, Bowker, & McKinnon, 1995; Williams et al., 2009). While the impact of fearful temperament on adjustment indices are regularly the focus of study, less well understood are biological and social processes that may affect the development of fearful temperament. The present study considered the role of the 5-HTTLPR polymorphism and parenting on change in fearful and inhibited temperamental characteristics during early childhood. The s/s genotype was expected to be associated with elevated and sustained levels of fearful temperament. Moreover, supportive parenting was expected to be associated with less fearful temperament while more harsh parenting would be associated with more fearful temperamental characteristics, especially for children with the s/s 5-HTTLPR genotype. Study hypotheses were tested using 165 families (i.e., biological mothers and fathers, 3-5 year old children) who participated in the Family Transitions Project (FTP: R. D. Conger & K. J. Conger, 2002). Children were genotyped using cheek swabs. Parents reported on children’s temperamental characteristics at ages 3, 4, and 5. Independent observations of mothers and fathers completing a puzzle with their 3 and 4 year old children were used to measure parenting. Results were partially supportive of predictions. Parenting interacted with the 5-HTTLPR genotype to predict trajectories of shyness and soothability dimensions of fearful temperament, but the pattern of findings varied for mothers and fathers. Results are discussed in terms of differential susceptibility and the conceptualization of risk and resilience.

Orientador: Lucia Galvão de Albuquerque / Banca: Mário Luiz Santana Júnior / Banca: Fernando Sebastian Baldi Rey / Banca: Ana Fabrícia Braga Magalhães / Banca: Roberto Carvalheiro / Abstract: Genotype-environment (GxE) interactions could be an important source of variation in reproductive traits with a striking effect on the onset of animal puberty. Thus, the objectives of the present study were: i) to assess the GxE interaction in Nellore sexual precocity indicator traits under different environmental conditions (EC) and ii) to identify, genomic regions and biological pathways associated to Nellore sexual precocity indicator traits and to investigate whether their effects changes according to EC levels. Phenotypic records for age at first calving (AFC), heifer early pregnancy (HP), heifer rebreeding (HR) and scrotal circumference (SC) were collected on 128,994; 85,339; 90,831 and 151,053 animals, respectively. From those, 1800 heifers, 3050 young bulls, and 800 sires were genotyped with BovineHD BeadChip. A reaction norm model was used to estimate the animal's response to environmental conditions changes. To assess the predictive ability the younger scheme and environment-specific scheme were used. For genome-wide scan, the SNP effects for reproductive traits were estimated in three EC levels: Low (EC = -3.0), Medium (EC = 0.0) and High (EC = 3.0) using a linear transformation of the genomic breeding values. The pleiotropic regions associated to reproductive traits (AFC, SC, HP and HR) in three EC levels, were identified using the statistical combination of the single-trait GWAS results and considered significant when -log10(p-valor)>6.0. The inclusion of genomic... (Complete abstract click electronic access below) / Resumo: A interação genótipo-ambiente (GxE) pode ser uma importante fonte de variação em características reprodutivas com um efeito notável no início da puberdade animal. Desta forma, os objetivos do presente estudo foram: i) Avaliar a interação GxE em características indicadores de precocidade sexual em animais da raça Nelore em diferentes condições ambientais (EC) e ii) identificar regiões genômicas e vias biológicas associadas a características indicadores de precocidade sexual e verificar se seus efeitos mudam de acordo com os níveis de EC. Informações fenotípicas para idade ao primeiro parto (AFC), ocorrência de prenhez precoce (HP), reconcepção de novilhas (HR) e perímetro escrotal (SC), foram coletados em 128.994, 85.339, 90.831 e 151.053 animais, respectivamente. Destes, 1800 novilhas, 3050 touros jovens e 800 touros foram genotipados com BovineHD BeadChip. Um modelo de norma de reação foi usado para estimar a resposta do animal às mudanças nas condições ambientais. Para avaliar a capacidade preditiva, foram utilizados os esquemas de validação em animais jovens e em ambiente específico. Para varredura genômica ampla os efeitos dos marcadores SNP para as características reprodutivas foram estimados em três níveis de EC Baixo (EC = -3.0), Médio (EC = 0.0) e Alto (EC = 3.0) usando uma transformação linear dos valores genômicos genéticos. As regiões pleiotrópicas associadas com características reprodutivas (AFC, SC, HP e HR) em três EC foram identificadas utilizando a combinação ... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Orientador: Sandra Helena Unêda Trevisoli / Banca: Ivana Marino Bárbaro Torneli / Banca: Viviane Formice Vianna / Resumo: A soja constitui-se na principal oleaginosa cultivada no mundo. Neste contexto, o Brasil se destaca como o segundo maior produtor mundial do grão. Dentre os muitos desafios encontrados pelo melhoramento genético, um dos principais está relacionado com a variação ambiental, que muitas vezes dificulta a seleção e recomendação de genótipos superiores. Sendo assim, faz-se necessário que os ensaios experimentais sejam conduzidos em vários ambientes, por vários anos para que possa ser analisado o comportamento quanto a adaptabilidade e estabilidade, visando futuras recomendações. Neste contexto, o objetivo do presente estudo consistiu em avaliar a desempenho agronômico, a adaptabilidade e estabilidade de genótipos de soja precoces. Os experimentos foram instalados em dois locais, a saber: localidade de Jaboticabal nos anos agrícolas 2012/2013, 2013/2014, 2015/2016 e 2016/2017 e localidade Piracicaba nos anos agrícolas 2014/2015 e 2015/2016. O delineamento utilizado foi de blocos ao acaso com três repetições. Foram avaliados os caracteres agronômicos número de dias para a maturidade e produtividade de grãos. Para estimar a adaptabilidade e estabilidade dos genótipos avaliados, foi utilizada a metodologia de Eberhart e Russell (1966). Desta maneira, foi possível detectar os genótipos mais responsivos e adaptados às regiões de cultivo. Para o caráter produtividade de grãos, merecem destaque os genótipos 4, 6,11, 26, 27, 29 e 34, sendo linhagens pertencentes ao programa de melhoramento... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Soy is the main oilseed crop in the world. In this context, Brazil stands out as the world's second largest producer of grain. Among the many challenges encountered by genetic improvement, one of the main challenges is related to environmental variation, which often hinders the selection and recommendation of higher genotypes. Thus, it is necessary that the experimental tests be conducted in several environments, for several years so that behavior can be analyzed for adaptability and stability, aiming at future recommendations. In this context, the objective of the present study was to evaluate the agronomic performance, adaptability and stability of early soybean genotypes. The experiments were installed in two locations, namely: Jaboticabal locality in the agricultural years 2012/2013, 2013/2014, 2015/2016 and 2016/2017 and locality Piracicaba in the agricultural years 2014/2015 and 2015/2016. The experimental design was a randomized block design with three replications. The agronomic characters were evaluated for the number of days for grain maturity and yield. To estimate the adaptability and stability of the evaluated genotypes, the methodology of Eberhart and Russell (1966) was used. In this way, it was possible to detect the genotypes more responsive and adapted to the growing regions. For grain yield, genotypes 4, 6, 11, 26, 27, 29 and 34 deserve special mention, being strains belonging to the soybean breeding program of UNESP Jaboticabal, all with averages above the ... (Complete abstract click electronic access below) / Mestre

The relationship between leaf and its environment has resulted in a tremendous diversification of leaf shape within and between plants species, which is important to cope with the differing environmental conditions. Arabidopsis lyrata is a prime model plant that shows leaf shape variation within species and between related species. In Cardamine and Capsella, the RCO genes (homeodomain leucine zipper family transcription factors) are involved in shaping leaves, yielding more complex shaped leaves (leaflets). In A. thaliana, over the course of evolution, the RCO-A and RCO-B paralogous genes have been deleted that led to the loss of lobes (leaf simplification). Based on previous quantitative trait locus (QTL) mapping results, these gene family members are thought to control leaf shape variation also in A. lyrata. Since the paralog involved in leaf shape variation is unknown, both copies of the RCO genes (AL6G13350 and AL6G13360) were sequenced. The study aimed to identify whether DNA sequence variation exists in the two paralogous RCO genes, which could explain the phenotype variation both within population and between A. lyrata populations, along with related species A. arenosa. The results showed limited variation in the coding regions in the form of indels, single nucleotide polymorphisms (SNPs) and amino acid substitutions resulting in no significant difference in phenotype between genotype (p>0.139). The most variants were rare and increasing the number of individuals within the populations, to cover the full phenotypic spectrum, may lead to different results. Not being able to obtain the nucleotide sequence of the promotor region, further analysis is required since it is an important region for gene expression, which could explain phenotype variation for leaf shape in Arabidopsis lyrata.

Em estudos de divergência genética por métodos multivariados, a distância euclidiana é a medida de distância mais amplamente utilizada e essa distância é a mais recomendada quando as unidades de cálculos são escores de componentes principais, como é o caso da análise AMMI (additive main effects and multiplicative interaction analysis). Tal análise permite a obtenção de estimativas mais precisas das respostas genotípicas e possibilita a análise da divergência genética por métodos aglomerativos. A análise dos modelos AMMI combina, num único modelo, componentes aditivos para os efeitos principais (genótipos e ambientes) e componentes multiplicativos para os efeitos da interação genótipos × ambientes. Os melhoristas de plantas compreendem que a interação genótipos × ambientes é de suma importância para a obtenção de variedades superiores e as estimativas de dissimilaridade atendem aos objetivos do melhorista, por quantificarem e informarem sobre o grau de semelhança ou de diferença entre pares de indivíduos. Entretanto, quando o número de indivíduos é grande, torna-se inviável o reconhecimento de grupos homogêneos pelo exame visual das estimativas de distância. Portanto, é importante proceder à análise de agrupamentos, obter dendrogramas por meio de métodos hierárquicos e posteriormente, analisar os grupos formados. A fim de determinar e classificar os grupos formados na clusterização hierárquica foram utilizados comandos específicos do programa computacional R que desenha no dendrograma os retângulos de cada grupo e os numera. Desta forma, o objetivo deste trabalho foi analisar a divergência genética via modelo AMMI, utilizando-se de técnicas multivariadas e reamostragem \"bootstrap\". / In studies of genetic diversity using multivariate approaches, the Euclidean distance is the most common measure used. This method is recommended when data are scores of principal components, such as in AMMI analysis (additive main effects and multiplicative interaction analysis). The AMMI method allows obtaining more precise estimates for genotypic results and also permits the use of genetic diversity analysis by using agglomerative approaches. Furthermore, this method combines additive components for the main effects (genotypes and environments) and multiplicative components for genotypes x environment interaction effects in a unique model. Plant breeders understand the importance of genotype and environment interaction to obtain superior varieties and the dissimilarity estimation meets breeders\" objectives since it quantifies and determines the similarity or the divergence between pairs of individuals. However, when the number of individuals is large it is unfeasible to recognize the group homogeneity by using a visual analysis of the distances estimation. Therefore, is important to use cluster analysis to obtain dendograms based on hierarchical methods and then analyze the groups obtained. In order to determine and classify the obtained groups from hierarchical cluster analysis specifics commands in the R software were used which shows in the dendrogram rectangles and numbers for each group. In this way, the objective of this work was to analyze the genetic divergence through AMMI model, by using multivariate approaches and \"bootstrap\" resampling.