O alcance de altas produtividades em milho (Zea mays L.) depende do desenvolvimento de híbridos, o principal produto explorado nos programas de melhoramento. O sucesso na obtenção deste tipo de cultivar é conseguido com extensivo cruzamento de linhagens, seguido de avaliações para identificação das combinações de maior potencial. Geralmente, o melhorista tem à sua disponibilidade grande número de linhagens, possibilitando a realização de centenas a milhares de cruzamentos distintos, dos quais apenas uma pequena quantidade pode ser avaliada experimentalmente devido a limitação de tempo e recursos. Com o advento da Seleção Genômica (GS) tornou-se possível predizer o comportamento destes indivíduos não avaliados com base em seu genoma. No decorrer do processo de consolidação da GS várias metodologias foram propostas. A aptidão destas em predizer desempenhos fenotípicos é dependente da sua capacidade de acomodar a arquitetura genética das características e lidar com a multicolinearidade das matrizes genômicas. Neste sentido, métodos baseados em modelos mistos podem apresentar menor eficiência na predição de características oligogênicas devido à não capacidade de representar a distribuição real do efeito dos QTL. Além disso, a regularização das predições na presença de multicolinearidade é realizada por meio de um parâmetro de penalização (λ), o qual pode ser estimado de várias formas e consequentemente modificar a acurácia dos modelos. Além do aprimoramento dos métodos, outro aspecto importante é o procedimento de correção dos dados fenotípicos previamente à GS, o qual não é consenso na comunidade científica. Diante do exposto, este trabalho objetivou: verificar o efeito das formas de obtenção do λ (via REML na GS e pela herdabilidade da característica) e da correção do fenótipo (valor genotípico e média ajustada) na GS e avaliar a eficiência da modelagem diferencial de QTL de maior efeito na capacidade preditiva da metodologia G-BLUP, comparando-a ao LASSO Bayesiano, BayesB e G-BLUP convencional. Para isso foram utilizadas informações de híbridos simples de milho tropical avaliados em cinco locais para produtividade de grãos, altura de planta e espiga no ano de 2015. Os dados genômicos foram obtidos com a plataforma Affymetrix® Axiom® Maize Genotyping Array de 616.201 SNPs. Foram estudados diferentes cenários de GS considerando os fatores supracitados, sendo estes comparados entre si por suas capacidades preditivas e seletivas. Os resultados obtidos indicam que a correção do fenótipo e a forma de estimação de λ afetam a capacidade preditiva. O uso de valores genotípicos como correção dos fenótipos e estimação de λ via REML apresentaram os melhores resultados. Foi também observado que a modelagem de SNPs de maior efeito como fator fixo aumenta discretamente a capacidade preditiva da metodologia G-BLUP para as características oligogênicas avaliadas (altura de planta e espiga), sendo indicado o uso do G-BLUP convencional. Complementarmente, observou-se que a GS apresentou modesta eficiência na seleção de híbridos superiores sob intensidades moderadas. Entretanto, a sua alta capacidade de selecionar sob baixa intensidade pode ser amplamente explorada nos programas de melhoramento de milho visando a seleção precoce direta. / The achievement of high yield in maize (Zea mays L.) relies on the development of hybrids, which is the main product of breeding programs. The success in obtaining this kind of cultivar is achieved through extensive crossing of inbred lines followed by field trials to identify the combinations with greatest potential. Generally, breeders have a large number of inbred lines on their hands, being able to perform hundreds to thousands of different crosses, of which only a small portion can be experimentally evaluated due to time and resource limitations. Genomic Selection (GS) has made it possible to predict phenotypes of unevaluated individuals based on their genome. Throughout the establishment process of GS many approaches have been proposed. The ability of these approaches at predicting phenotypic performance depends on their capacity of accommodating the genetic architecture of the traits and dealing with the multicollinearity of the genomic matrices. Hence, methods based on mixed model equations may present lower prediction efficiency for oligogenic traits due to their inability of depicting the real distribution of the QTL effects. Moreover, the prediction regularization in the presence of multicollinearity is done by a shrinkage factor (λ), which can be estimated in a number of ways and may affect the accuracy of the models. In addition to the improvement of the models, the correction of the phenotype utilized in the predictions is also important, which is not a consensus among researchers. Based on these facts, this study aimed to assess the effect of estimation of λ (by REML in the GS model and by the heritability of the traits) and the correction of the phenotype (genotypic value and adjusted mean) on the GS. It also targeted to evaluate the effect of differential modeling of major makers on the prediction accuracy of G-BLUP, comparing it to Bayesian LASSO, BayesB and ordinary G-BLUP. To those ends, tropical maize single-crosses evaluated at five sites for grain yield, plant and ear height in 2015 were utilized. The genomic data was obtained with the Affymetrix® Axiom® Maize Genotyping Array of 616,201 SNPs. Distinct GS scenarios were studied considering the aforementioned factors which were compared by their prediction and selection accuracy. The results suggest that the correction of the phenotype and the way of estimation of λ do affect prediction accuracies. The use of genotypic values as the correction of phenotypes and the estimation of λ by REML showed best results. It was also observed that modeling major SNPs as fixed effect factors had little improvement on the prediction accuracy of G-BLUP for the oligogenic traits evaluated (plant and ear height). Thereby, ordinary G-BLUP should be the method of choice to predict these traits. Additionally, it was observed that GS presented modest efficiency for selecting superior hybrids under moderate intensities. However, its high effectiveness at selecting under low intensities might be exploited on maize breeding programs for early direct selection.

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.

No description available.

Comment la diversification biologique peut-elle avoir lieu malgré les échanges génétiques? Comment les barrières reproductives entre espèces évoluent-elles et fonctionnent-elles? Les changements adaptatifs de certains traits favorisent-ils la diversification et la spéciation? Ces questions ouvertes en biologie évolutive constituent la base de ce projet. Pour y répondre, nous nous sommes intéressés aux papillons du genre néo-tropical Heliconius qui constituent une partie importante des communautés diversifiées de papillons néotropicaux. Les papillons de ce groupe sont immangeables pour les prédateurs, arborent des colorations d’avertissement qui signalent leur toxicité, et miment d’autres papillons toxiques dans leurs communautés locales. Ce genre a connu une radiation adaptative des motifs colorés soumis à la sélection naturelle favorisant le mimétisme de divers signaux locaux, mais ces motifs sont également connus comme signaux intraspécifiques favorisant les appariements homogames. Mes travaux ont permis d’approfondir les connaissances actuelles sur la fonction écologique et la base génétique de la couleur des ailes chez ces papillons, et d’explorer l'importance de la couleur des ailes par rapport aux signaux chimiques au cours des premières étapes de diversification. Dans cette optique, j’ai caractérisé la divergence adaptive entre les taxons à différents stades du continuum de spéciation, par une approche intégrative combinant des données génomiques, phénotypiques, comportementales, chimiques et écologiques. Plus précisément, j’ai étudié le sous-clade de Heliconius appelé sylvaniformes, contenant des espèces de papillons aux motifs tigrés, qui participent à des relations de mimétisme avec de nombreuses autres espèces fortement apparentées ou non. Mes travaux incluent la description comparative de l'architecture génétique des motifs colorés adaptatifs parallèlement chez les espèces H. hecale et H. ismenius, en utilisant des croisements, du génotypage génomique à haut débit, et de la morphométrie des motifs colorés. J’ai également exploré l'importance de la sélection naturelle et sexuelle sur les locus contrôlant ces motifs colorés aux stades précoces de divergence dans ce genre. En particulier, j’ai analysé la structure et le maintien de la zone d’hybridation entre deux races parapatriques de H. hecale montrant des colorations différentes, en combinant la génétique et la génomique des populations, ainsi que l’analyse phénotypique de clines et des tests comportementaux sur le choix de partenaire chez les mâles. Enfin, j’ai effectué des analyses génomiques de la divergence et du flux de gènes en me basant sur des données de re-séquençage de génomes complets afin de rechercher des traces d'introgression entre des espèces co-mimétiques et étroitement apparentées. Ceci a été également couplé à des expériences de préférence et de comportement sexuel, ainsi qu’à des analyses chimiques montrant d'importantes différences dans des composés qui pourraient intervenir dans la reconnaissance spécifique et le maintien des limites entre espèces. Dans l'ensemble, mes travaux montrent que bien que la sélection agissant sur les motifs colorés des ailes ait été centrale dans la diversification du genre Heliconius, l'accumulation d'autres barrières au flux de gènes peut jouer un rôle important dans l’aboutissement du processus de spéciation. / How does biological diversification occur in the face of genetic exchange? How do reproductive barriers evolve and function? What is the role of adaptive traits in promoting diversification and speciation? These open questions in evolutionary biology are at the core of this project. In order to tackle them, we have focused on butterflies in the neo-tropical genus which are an important component of the diverse butterfly communities in the Neo-tropics. Butterflies in the genus Heliconius are unpalatable to predators, use warning colours to advertise their defences, and mimic other defended butterflies in their local communities. The genus has undergone an adaptive radiation in wing colour patterns as a result of natural selection for mimicry, and is also well known for assortative mating based on wing pattern. I have extended the current knowledge about the ecological function and the genetic basis of wing color patterns in these butterflies and explored the importance of wing coloration relative to chemical signaling in the early stages of diversification. To this aim, I have characterised the adaptive divergence between lineages at different stages of the speciation continuum, by integrating genomic, phenotypic, behavioural, chemical and ecological data. More precisely, I have studied the so-called silvaniform sub-clade of Heliconius, known for harbouring species with tiger patterns that participate in mimicry with large groups of other closely and distantly-related species. My work includes the comparative description of the genetic architecture of wing pattern adaptation in two species, H. hecale and H. ismenius, using crosses, genome-wide next-generation genotyping, and advanced morphometrics of colour patterns. I have also explored the importance of natural and sexual selection on wing-patterning loci at early stages of divergence in the genus. In particular, I have analysed the structure and maintenance of a hybrid zone between two distinctly coloured parapatric races of H. hecale by using a combination of population genetics and genomics, coupled to a phenotypic analysis of the clines and to behavioural assays on male-based mate choice. Finally, I have carried out genome-wide analyses of divergence and gene flow with whole genome sequencing data to look for evidence of introgression between coexisting, hybridising co-mimetic species. This was again coupled to experiments on mating preferences and behavior, and yielded evidence for important differences in putative pheromone signals which may mediate species recognition and the maintenance of species boundaries. Overall, my results show that although selection on wing pattern divergence have been central to the diversification of the genus Heliconius, the accumulation of other barriers to gene flow may be important for the speciation process to be completed.

Nas regiões tropicais os solos apresentam diferentes níveis de acidez. Assim, o estudo da herança dos caracteres de importância econômica no milho nas regiões tropicais é necessário para se delinear os programas de melhoramento para os diferentes níveis de acidez do solo. Atualmente, o estudo da arquitetura dos caracteres quantitativos tem sido realizado através do mapeamento de QTLs. Nos programas de melhoramento de milho, linhagens de populações de melhoramento são cruzadas com linhagens elites (testadores) e os testecrosses são utilizados para avaliar o potencial genético de cada linhagem para o desenvolvimento de híbridos. O objetivo deste estudo foi mapear QTLs em testecrosses avaliados sob diferentes níveis de acidez do solo. Duzentas e cinqüenta e seis plantas F2, obtidas do cruzamento das linhagens L 14-04B e L 08-05F, foram genotipadas com marcadores microssatélites para a construção de um mapa genético. As 256 plantas F2 foram autofecundadas e suas respectivas progênies F2:3 foram cruzadas com os testadores L 04-05F e L 02-03D. Os testecrosses foram avaliados em três tipos de solos: solo não ácido (SNA), solo de moderada acidez (SMA) e solo de alta acidez (SAA) em três anos agrícolas em Piracicaba, SP, em látices simples 16 x 16. Foram avaliados os caracteres: produção de grãos (PG), acamamento e quebramento de plantas (ACQ), prolificidade (PROL), alturas de planta (AP) e de espiga (AE), posição relativa de espiga (PRE), florescimento masculino (FM) e feminino (FF) e intervalo entre florescimentos (IF). O método de mapeamento por intervalo composto expandido para múltiplos ambientes foi utilizado para o mapeamento de QTLs e para detectar a interação QTL x acidez do solo. O número de QTLs mapeados diferiu de acordo com o testador utilizado; por exemplo, para PG foram mapeados 20 e 39 QTLs nos testecrosses da linhagem L 04-05F (TC1) e nos testecrosses da linhagem L 02-03D (TC2), respectivamente. Houve uma grande variação nas variâncias fenotípicas explicadas pelos QTLs; por exemplo, para PG houve uma variação de 0,01% a 5,29% e para AP houve uma variação de 0,01% a 13,54%. Foram mapeados QTLs em todos os cromossomos para a PG, ACQ e PROL; e para os outros caracteres foram mapeados QTLs na maioria dos cromossomos. A maioria dos QTLs mapeados para todos os caracteres interagiu com a acidez do solo. Por exemplo, para PG cerca de 80,00% dos QTLs mapeados apresentaram interação com a acidez do solo, enquanto que para os outros caracteres a porcentagem de QTLs que interagiu com a acidez do solo variou de 50,00% para FM a 93,03% para ACQ. O grande número de QTLs que interagiu com a acidez do solo é um sério desafio para a aplicação da seleção assistida por marcadores moleculares em programas de melhoramento de milho em regiões tropicais. / In tropical maize cropping areas the soils present different levels of acidity. Thus, to study the inheritance of maize traits for these areas it is necessary to conduct experiments under different levels of soil acidity. Nowadays the architecture of the polygenic traits has been assessed by means of QTL mapping. Also, in applied breeding programs, experimental lines are crossed to elite lines (testers), and the testcrosses are used to assess their genetic potential for hybrid development. The objective of this research was to map QTLs in testcrosses evaluated under three levels of soil acidity. Two hundred and fifty six F2 plants, developed from the cross between the inbreds lines L14-04B and L08-05F, were genotyped with microsatellite markers to construct a genetic map. The 256 F2 plants were selfed and their respective F2:3 progenies were testcrossed to the testers L04-05F and L02-03D, and these testcrosses were evaluated in three types of soils: non-acid soil (NAS), moderate acitity soil (MAS) and high acidity soil (HAS) in three cropping seasons in Piracicaba, SP, in 16 x 16 simple lattices. The traits recorded were: grain yield (GY), plant lodging (PL), prolificacy (PRO), plant (PH) and ear heights (EH), ear placement (EP), days to anthesis (DA), days to silking (DS), and anthesis-silking interval (ASI). The composite interval mapping extended to multiple environment was used to map QTLs and to detect QTL x soil interaction. The number of QTLs mapped was different for each tester; for instance, for GY, 20 and 39 QTLs were mapped in the testcrosses with L04-05F and L02-03D, respectively. The range of the phenotypic variance explained by the QTLs was very large for all traits; for instance for GY the range was from 0.01% to 5.29% and for plant height it was from 0.01% to 13.54%. QTLs were mapped in all chromosomes for GY, PL, and PRO; and for the other traits QTLs were mapped in almost all chromosomes. Most of the QTLs mapped for all traits interacted significantly with soil acidity. For instance, for GY about 80.00% of the QTLs mapped interacted with soil acidity, whereas for the other traits the percentage of the QTLs that interacted with soil acidity ranged from 50.00% for DS to 93.03% to PL. The high number of the QTLs that interacted with soil acidity imposes a serious challenge for marker assisted selection in maize breeding programs for tropical regions.

Made available in DSpace on 2016-06-02T20:21:24Z (GMT). No. of bitstreams: 1 3223.pdf: 1875073 bytes, checksum: da879cb2bcfcd8ac244156eec8eca3ad (MD5) Previous issue date: 2010-08-05 / Universidade Federal de Minas Gerais / Genetic architecture of a phenotype represents the total number of genes, independent effects (additivity), the interactions between alleles (dominance and epistasis), and its effects on other phenotypes (pleiotropy). An enormous debate about general types of genetic architectures relates the importance of independent and interactive variation in the adaptive process. Because natural selection reduces additive variation, we expect, of fitness related phenotypes, lesser additive than interactive variation and relatively more genes with moderate effects. Maternal care is a phenotype with enormous importance to fitness. Of the maternal care behaviors, the nest building highlights itself improving pups survival by protection against predators and temperature maintenance. We investigated the genetic architecture of nest building in mice and tested the hypothesis that this behavior has a genetic architecture related to fitness, also verifying possible associations with anxiety and weight. For that, we checked the relation between all phenotypes and tested, using the QTL analysis, the phenotypic association with regions (microsatellites markers) spread about all genome of F2 females at maternal stage from the intercross of inbred strains SM/J and LG/J. We found 23 QTLs which, individually, are associated with phenotypic variation on nest building, weight and anxiety (15 QTLs at the 6 nest building phenotypes). The nest building s individual QTLs have moderate effects (from 4 to 13%), and the numerous epistatic QTLs add to increase this explained variation. There are common regions for nest building with anxiety and weight and, searching for candidate genes, we found genes with effects already described for these phenotypes. Hence, we corroborate our hypothesis of the genetic architecture type related to fitness for nest building behavior, of genes with bigger effects and high interactive variation. The identification of regions associated with maternal care in mice and the knowledge of the related genetic architecture can help in identifying genes for these behaviors in other mammals, and in the comprehension of general patterns in adaptive process and life evolution. / Arquitetura genética de um fenótipo representa o número total de genes, os efeitos independentes (aditividade), as interações entre alelos (dominância e epistasia), e o efeito destes em outros fenótipos (pleiotropia). Um grande debate entre tipos gerais de arquitetura genética está no papel da variação independente e de interações no processo adaptativo. Pela seleção natural reduzir a variação aditiva, esperamos de fenótipos ligados ao fitness menor variação aditiva relativa a variação de interações e genes com efeitos médios relativamente mais comuns. O cuidado materno é um fenótipo com grande importância para o fitness. Dentre os comportamentos de cuidado materno, a construção de ninho destaca-se aumentando a sobrevivência dos filhotes pela proteção contra predadores e manutenção da temperatura. Investigamos a arquitetura genética da construção de ninho em camundongos e testamos a hipótese que esse comportamento tem a arquitetura genética relacionada ao fitness, verificando também possíveis associações com ansiedade e peso. Para isso, checamos as relações entre os fenótipos e testamos, com a análise de QTL, a associação dos fenótipos com regiões (marcadores microssatélites) por todo o genoma de fêmeas F2 em fase materna do intercruzamento das linhagens endogâmicas SM/J e LG/J. Obtivemos 23 QTLs que, individualmente, estão associados com a variação nos fenótipos de construção de ninho, peso e ansiedade (15 QTLs para os 6 fenótipos de construção de ninho). Os QTLs individuais de construção de ninho têm efeitos moderados (de 4 a 13%), e os muitos QTLs epistáticos colaboram aumentando essa variação explicada. Existem regiões em comum para ninho com peso e ansiedade e, na procura de genes candidatos, descobrimos genes já descritos com efeitos nesses fenótipos. Assim, corroboramos a hipótese do tipo de arquitetura genética relacionada ao fitness para o comportamento de construção de ninho, de genes com grandes efeitos e alta variação genética de interações. A identificação de regiões associadas ao cuidado materno em camundongos e o entendimento da arquitetura genética envolvida poderão contribuir na identificação de genes para esses comportamentos em outros mamíferos, e na compreensão do padrão geral do processo adaptativo e da evolução dos seres vivos.

Nas regiões tropicais os solos apresentam diferentes níveis de acidez. Assim, o estudo da herança dos caracteres de importância econômica no milho nas regiões tropicais é necessário para se delinear os programas de melhoramento para os diferentes níveis de acidez do solo. Atualmente, o estudo da arquitetura dos caracteres quantitativos tem sido realizado através do mapeamento de QTLs. Nos programas de melhoramento de milho, linhagens de populações de melhoramento são cruzadas com linhagens elites (testadores) e os testecrosses são utilizados para avaliar o potencial genético de cada linhagem para o desenvolvimento de híbridos. O objetivo deste estudo foi mapear QTLs em testecrosses avaliados sob diferentes níveis de acidez do solo. Duzentas e cinqüenta e seis plantas F2, obtidas do cruzamento das linhagens L 14-04B e L 08-05F, foram genotipadas com marcadores microssatélites para a construção de um mapa genético. As 256 plantas F2 foram autofecundadas e suas respectivas progênies F2:3 foram cruzadas com os testadores L 04-05F e L 02-03D. Os testecrosses foram avaliados em três tipos de solos: solo não ácido (SNA), solo de moderada acidez (SMA) e solo de alta acidez (SAA) em três anos agrícolas em Piracicaba, SP, em látices simples 16 x 16. Foram avaliados os caracteres: produção de grãos (PG), acamamento e quebramento de plantas (ACQ), prolificidade (PROL), alturas de planta (AP) e de espiga (AE), posição relativa de espiga (PRE), florescimento masculino (FM) e feminino (FF) e intervalo entre florescimentos (IF). O método de mapeamento por intervalo composto expandido para múltiplos ambientes foi utilizado para o mapeamento de QTLs e para detectar a interação QTL x acidez do solo. O número de QTLs mapeados diferiu de acordo com o testador utilizado; por exemplo, para PG foram mapeados 20 e 39 QTLs nos testecrosses da linhagem L 04-05F (TC1) e nos testecrosses da linhagem L 02-03D (TC2), respectivamente. Houve uma grande variação nas variâncias fenotípicas explicadas pelos QTLs; por exemplo, para PG houve uma variação de 0,01% a 5,29% e para AP houve uma variação de 0,01% a 13,54%. Foram mapeados QTLs em todos os cromossomos para a PG, ACQ e PROL; e para os outros caracteres foram mapeados QTLs na maioria dos cromossomos. A maioria dos QTLs mapeados para todos os caracteres interagiu com a acidez do solo. Por exemplo, para PG cerca de 80,00% dos QTLs mapeados apresentaram interação com a acidez do solo, enquanto que para os outros caracteres a porcentagem de QTLs que interagiu com a acidez do solo variou de 50,00% para FM a 93,03% para ACQ. O grande número de QTLs que interagiu com a acidez do solo é um sério desafio para a aplicação da seleção assistida por marcadores moleculares em programas de melhoramento de milho em regiões tropicais. / In tropical maize cropping areas the soils present different levels of acidity. Thus, to study the inheritance of maize traits for these areas it is necessary to conduct experiments under different levels of soil acidity. Nowadays the architecture of the polygenic traits has been assessed by means of QTL mapping. Also, in applied breeding programs, experimental lines are crossed to elite lines (testers), and the testcrosses are used to assess their genetic potential for hybrid development. The objective of this research was to map QTLs in testcrosses evaluated under three levels of soil acidity. Two hundred and fifty six F2 plants, developed from the cross between the inbreds lines L14-04B and L08-05F, were genotyped with microsatellite markers to construct a genetic map. The 256 F2 plants were selfed and their respective F2:3 progenies were testcrossed to the testers L04-05F and L02-03D, and these testcrosses were evaluated in three types of soils: non-acid soil (NAS), moderate acitity soil (MAS) and high acidity soil (HAS) in three cropping seasons in Piracicaba, SP, in 16 x 16 simple lattices. The traits recorded were: grain yield (GY), plant lodging (PL), prolificacy (PRO), plant (PH) and ear heights (EH), ear placement (EP), days to anthesis (DA), days to silking (DS), and anthesis-silking interval (ASI). The composite interval mapping extended to multiple environment was used to map QTLs and to detect QTL x soil interaction. The number of QTLs mapped was different for each tester; for instance, for GY, 20 and 39 QTLs were mapped in the testcrosses with L04-05F and L02-03D, respectively. The range of the phenotypic variance explained by the QTLs was very large for all traits; for instance for GY the range was from 0.01% to 5.29% and for plant height it was from 0.01% to 13.54%. QTLs were mapped in all chromosomes for GY, PL, and PRO; and for the other traits QTLs were mapped in almost all chromosomes. Most of the QTLs mapped for all traits interacted significantly with soil acidity. For instance, for GY about 80.00% of the QTLs mapped interacted with soil acidity, whereas for the other traits the percentage of the QTLs that interacted with soil acidity ranged from 50.00% for DS to 93.03% to PL. The high number of the QTLs that interacted with soil acidity imposes a serious challenge for marker assisted selection in maize breeding programs for tropical regions.

L'un des objectifs centraux de la biologie est de comprendre comment l'ADN, la séquence primaire, donne lieu à des traits observables. À cette fin, nous examinons ici des méthodes pour identifier les composants génétiques qui influencent les traits microbiens. Par « identifier », nous entendons l'élucidation à la fois l'état allélique et de la position physique de chaque variante causale d'un phénotype d'intérêt à la résolution des nucléotides de paires de bases. Nous nous sommes concentrés sur les études d'association génomique (genome-wide association studies; GWAS) en tant qu'approche générale d’étudier l'architecture génétique des traits. L'objectif global de cette thèse était d'examiner de manière critique les méthodologies GWAS et de les considérer en pratique dans des populations microbiennes fortement clonales et non- clonales (i.e. avec recombinaison fréquent). Le domaine de la GWAS microbienne est relativement nouveau par rapport aux quinze dernières années de la GWAS humaine, et en tant que tel, nous avons commencé par un examen de l'état de la GWAS microbienne. Nous avons posé deux questions principales : 1) Les méthodes GWAS humaines fonctionnent-elles facilement et sans modification pour les populations microbiennes ? 2) Et sinon, quels sont les problèmes méthodologiques centraux et les modifications nécessaires pour la GWAS microbienne? À partir de ces résultats, nous avons ensuite détaillé le déséquilibre de liaison (linkage disequilibrium; LD) comme principal obstacle dans la GWAS microbien, et nous avons présenté une nouvelle méthode, POUTINE, pour relever ce défi en exploitant les mutations homoplasiques pour briser implicitement la structure LD. Le reste de la thèse présente à la fois les méthodes traditionnelles GWAS (comptage des allèles) et POUTINE (comptage d’homoplasies) appliquées à une population hautement recombinogène de génomes de vibrions marins. Malgré une taille d'échantillon modeste, nous donnons un premier aperçu de l'architecture génétique de la résistance aux bactériophages dans une population naturelle, tout en montrant que les récepteurs des bactériophages jouent un rôle primordial. Ce résultat est en pleine cohérence avec des expériences en laboratoire de coévolution phage-bactérie. Il est important de noter que cette architecture met en évidence à quel point la sélection positive peut sculpter certains traits microbiens différemment de nombreux traits complexes humains, qui sont généralement soumis à une faible sélection purificatrice. Plus précisément, nous avons identifié des mutations à effet important à haute fréquence qui sont rarement observées dans les phénotypes complexes humains où de nombreuses mutations à faible effet contribuent à l'héritabilité. La thèse se termine par des perspectives sur les voies à suivre pour la GWAS microbienne. / One of the central goals of biology is to understand how DNA, the primary sequence, gives rise to observable traits. To this aim, we herein examine methods to identify the genetic components that influence microbial traits. By "identify" we mean the elucidation of both the allelic state and physical position of each causal variant of a phenotype of interest down to the base-pair nucleotide resolution. Our focus has been on genome-wide association studies (GWAS) as a general approach to dissecting the genetic architecture of traits. The overarching aim of this thesis was to critically examine GWAS methodologies and to consider them in practice in both strongly clonal and highly recombining microbial populations. The field of microbial GWAS is relatively new compared to the over fifteen years of human GWAS, and as such, we began this work with an examination of the state of microbial GWAS. We asked and attempted to answer two main questions: 1) Do human GWAS methods readily work without modification for microbial populations? 2) And if not, what are the central methodological problems and changes that are required for a successful microbial GWAS? Building from these findings, we then detailed linkage disequilibrium (LD) as the primary obstacle in microbial GWAS, and we presented a new method, POUTINE, to address this challenge by harnessing homoplasic mutations to implicitly break LD structure. The remainder of the thesis showcases both traditional GWAS methods (allele counting) and POUTINE applied to a highly recombining population of marine vibrio genomes. Despite a small sample size, we provide a first glimpse into the genetic architecture of bacteriophage resistance in a natural population and show that bacteriophage receptors play a primary role consistent with experimental populations of phage-bacteria coevolution. Importantly, this architecture highlights how strong positive selection can sculpt some microbial traits differently than many human complex traits, which are generally under weak purifying selection. Specifically, we identified common frequency, large-effect mutations that are rarely observed in human complex phenotypes where many low-effect mutations are thought to contribute to the bulk of heritability. The thesis concludes with perspectives on ways forward for microbial GWAS.

In dieser Arbeit wird eine neue Methode für den skalenunabhängigen Vergleich von LD-Strukturen in unterschiedlichen genomischen Regionen vorgeschlagen. Verschiedene Aspekte durch Skalen verursachter Probleme – von der Präzision der Schätzung der Marke-reffekte bis zur Genauigkeit der Vorhersage für neue Individuen - wurden untersucht. Darüber hinaus, basierend auf den Leistungsvergleichen von unterschiedlichen statistischen Methoden, wurden Empfehlungen für die Verwendungen der untersuchten Methoden gege-ben. / In dieser Arbeit wird eine neue Methode für den skalenunabhängigen Vergleich von LD-Strukturen in unterschiedlichen genomischen Regionen vorgeschlagen. Verschiedene Aspekte durch Skalen verursachter Probleme – von der Präzision der Schätzung der Marke-reffekte bis zur Genauigkeit der Vorhersage für neue Individuen - wurden untersucht. Darüber hinaus, basierend auf den Leistungsvergleichen von unterschiedlichen statistischen Methoden, wurden Empfehlungen für die Verwendungen der untersuchten Methoden gegeben

The aetiology of common diseases is shaped by the effects of genetic and environmental factors. Big efforts have been devoted to unravel the genetic basis of disease with the hope that it will help to develop new therapeutic treatments and to achieve personalized medicine. With the development of high-throughput genotyping technologies, hundreds of association studies have described many loci associated to disease. However, the depiction of disease architecture remains incomplete. The aim of this work is to perform exhaustive comparisons across human populations to evaluate pressing questions. Our results provide new insights in the allele frequency of risk variants, their sharing across populations and the likely architecture of disease / La etiología de las enfermedades comunes está formada por factores genéticos y ambientales. Se ha puesto mucho empeño en describir sus bases genéticas. Este conocimiento será útil para desarrollar nuevas terapias y la medicina personalizada. Gracias a las técnicas de genotipado masivo, centenares de estudios de asociación han descrito una infinidad de genes asociados a enfermedad. Pese a ello, la arquitectura genética de las enfermedades no ha sido totalmente descrita. Esta tesis pretende llevar a cabo exhaustivas comparaciones entre poblaciones para responder diversas preguntas candentes. Nuestros resultados dan pistas sobre la frecuencia de los alelos de riesgo, su presencia entre poblaciones y la probable arquitectura de las enfermedades.