abstract: Building mathematical models and examining the compatibility of their theoretical predictions with empirical data are important for our understanding of evolution. The rapidly increasing amounts of genomic data on polymorphisms greatly motivate evolutionary biologists to find targets of positive selection. Although intensive mathematical and statistical studies for characterizing signatures of positive selection have been conducted to identify targets of positive selection, relatively little is known about the effects of other evolutionary forces on signatures of positive selection. In this dissertation, I investigate the effects of various evolutionary factors, including purifying selection and population demography, on signatures of positive selection. Specifically, the effects on two highly used methods for detecting positive selection, one by Wright's Fst and its analogues and the other by footprints of genetic hitchhiking, are investigated. In Chapters 2 and 3, the effect of purifying selection on Fst is studied. The results show that purifying selection intensity greatly affects Fst by modulating allele frequencies across populations. The footprints of genetic hitchhiking in a geographically structured population are studied in Chapter 4. The results demonstrate that footprints of genetic hitchhiking are significantly influenced by geographic structure, which may help scientists to infer the origin and spread of the beneficial allele. In Chapter 5, the stochastic dynamics of a hitchhiking allele are studied using the diffusion process of genetic hitchhiking conditioned on the fixation of the beneficial allele. Explicit formulae for the conditioned two-locus diffusion process of genetic hitchhiking are derived and stochastic aspects of genetic hitchhiking are investigated. The results in this dissertation show that it is essential to model the interaction of neutral and selective forces for correct identification of the targets of positive selection. / Dissertation/Thesis / Ph.D. Biology 2011

abstract: Collaborative learning is a common teaching strategy in classrooms across age groups and content areas. It is important to measure and understand the cognitive process involved during collaboration to improve teaching methods involving interactive activities. This research attempted to answer the question: why do students learn more in collaborative settings? Using three measurement tools, 142 participants from seven different biology courses at a community college and at a university were tested before and after collaborating about the biological process of natural selection. Three factors were analyzed to measure their effect on learning at the individual level and the group level. The three factors were: difference in prior knowledge, sex and religious beliefs. Gender and religious beliefs both had a significant effect on post-test scores. / Dissertation/Thesis / Ph.D. Curriculum and Instruction 2012

abstract: The Modern Synthesis embodies a theory of natural selection where selection is to be fundamentally understood in terms of measures of fitness and the covariance of reproductive success and trait or character variables. Whether made explicit or left implicit, the notion that selection requires that some trait variable cause reproductive success has been deemphasized in our modern understanding of exactly what selection amounts to. The dissertation seeks to advance a theory of natural selection that is fundamentally causal. By focusing on the causal nature of natural selection (rather than on fitness or statistical formulae), certain conceptual and methodological problems are seen in a new, clarifying light and avenues toward new, interesting solutions to those problems are illustrated. First, the dissertation offers an update to explicitly causal theories of when exactly a trait counts as an adaptation upon fixation in a population and draws out theoretical and practical implications for evolutionary biology. Second, I examine a case of a novel character that evolves by niche construction and argue that it evolves by selection for it and consider implications for understanding adaptations and drift. The third contribution of the dissertation is an argument for the importance of defining group selection causally and an argument against model pluralism in the levels of selection debate. Fourth, the dissertation makes a methodological contribution. I offer the first steps toward an explicitly causal methodology for inferring the causes of selection—something often required in addition to inferring the causes of reproductive success. The concluding chapter summarizes the work and discusses potential paths for future work. / Dissertation/Thesis / Doctoral Dissertation Biology 2016

Depuis plusieurs décennies, les populations font face à des changements environnementaux sans précédent. Afin de répondre à ces changements les espèces peuvent se déplacer vers un autre endroit (c’est la dispersion), répondre aux changements par plasticité phénotypique, ou encore s’adapter par sélection naturelle (c’est la réponse évolutive). Si la dispersion et la plasticité phénotypique permettent une réponse rapide face à un changement environnemental tel que le réchauffement climatique, seule la réponse évolutive permet une adaptation durable. Une réponse évolutive au changement climatique peut être attendue seulement si l'augmentation des températures occasionne une pression de sélection sur un et / ou des traits. Cependant, quantifier les pressions de sélection qui agissent sur les populations naturelles reste difficile, en particulier celles qui accompagnent le changement climatique.Au cours de cette thèse, j'ai cherché à quantifier les pressions de sélection reliées au changement climatique agissant sur une population sauvage de mésange bleue (Cyanistes caeruleus) suivie depuis 26 ans près de Montpellier. Dans un premier temps, j'ai exploré le biais induit par l'autocorrélation spatiale sur l'estimation de la sélection naturelle lorsqu'elle n'est pas prise en compte dans une population sauvage. Dans un deuxième temps, j'ai quantifier l'impact du réchauffement climatique sur la force de sélection agissant sur la date de ponte, un trait fortement relié au succès reproducteur chez la mésange bleue. Cependant, si le changement climatique est caractérisé par une augmentation des températures, il s'accompagne aussi d'une augmentation de la fréquence d'évènements extrêmes climatique (EEC). Dans un troisième temps, je me suis donc attaché à estimer l'influence des températures et des pluies extrêmes sur la force de la sélection naturelle. Concernant l'autocorrélation spatiale, nos résultats ont permit de mettre en avant un biais majeur sur l'estimation de la sélection naturelle lorsqu'elle n'est pas prise en compte. En effet, lorsque la valeur sélective est positivement spatialement autocorrélée, un modèle de sélection non-spatialisé surestimera la force de la sélection naturelle agissant sur les traits. Nous avons donc développé 4 modèles de sélection spatialisés, et nous les avons comparé entre eux sur la base de plusieurs paramètres. De plus, nous avons détecté un fort réchauffement dans notre population qui s'accompagnait d'une augmentation de la force de sélection naturelle agissant sur la date de ponte. En effet, nous avons quantifié une augmentation de 46% de la force de sélection naturelle tout les +1°C de la température maximum du mois d'Avril. Au delà des températures moyennes, nous avons mis en évidence un fort impact négatif de la présence / absence de journées extrêmement chaudes durant l'élevage des oisillons au nid sur le succès d'envol. Plus intéressant encore, ces EECs augmentaient significativement la force de sélection naturelle agissant sur la date de ponte, indépendamment de l'augmentation des températures moyennes.Ainsi, ma thèse a contribué à une meilleure compréhension méthodologique de la sélection naturelle, ainsi que de l'impact sélectif du changement climatique. Le premier chapitre a permit de mettre en évidence un problème méthodologique majeur lorsque on estime la sélection naturelle dans les populations sauvages, ainsi que de proposer des solutions concrètes. Le second chapitre a permit de confirmer l'impact sélectif du changement climatique, laissant entrevoir une possibilité de réponse évolutive au réchauffement. Enfin, le troisième chapitre démontrait la sélection naturelle reliée à l'apparition d'EEC, et en quantifiait les effets, un résultats encore jamais montré. Nous espérons que cette thèse ouvrira la voie à plus d'études explorant l'impact du changement climatique sur la sélection naturelle, permettant peut être de prévoir les réponses évolutives futures. / Global change results in an increase in temperature mean and variability and generates new environmental conditions for wild populations. In order to respond to this new treat, wild populations can move to another place (dispersion), change their behaviour or their phenology (phenotypic plasticity) or respond by evolutionary change (involving changes in alleles frequency). However, phenotypic plasticity or dispersion are unlikely to sustain population responses to climate change over the long term, contrary to the evolutionary response. Wild populations could evolutionary respond to climate change only if the increase in temperature represents a selective pressure on fitness-related traits. Yet, quantifying the selective pressures acting on wild populations remains challenging, especially in response to climate change.During this PhD, I focused on the selection pressures related to climate warming during a 26-year monitoring of blue tits (Cyanistes caeruleus) in southern France. First, I explored the bias inducted by spatial autocorrelation on estimation of natural selection in the wild when it is not taken into account. Second, I quantified the impact of climate warming on natural selection acting on laying date. Along with a rise in mean temperatures, climate change is also characterized by an increase in the frequency of extreme climatic events (ECE). Hence, I finally explored the impact of multiple ECEs such heavy rainfalls and extremes temperatures on the strength of natural selection acting on laying date.Our results showed that spatial autocorrelation is severely biasing our estimation of natural selection in the wild if it is not taken into account. In fact, natural selection is continuously overestimated by a non-explicit spatial model when the fitness is spatially autocorrelated. Hence, we developed 4 spatially-explicit models of selection, and we compared them in order to assess their reliability. Also, we detected a strong warming in our study site, which was correlated with an increase in natural selection strength. In fact, our results indicated an increase in the strength of selection by 46% every +1°C anomalies in maximum April temperature. Beyond this selective impact of the warming trend, we detected an impact of the extreme hot days occurrence during the nestlings stage on the fledglings success. More interesting, these ECEs significantly increased the strength of selection acting on laying date, independently form the mean temperatures.To conclude, my PhD helped to a better understanding of natural selection estimation in the wild, and the selective impact of climate warming. The first part allowed to develop specific models of selection in order to take into account spatial autocorrelation, a universal phenomenon present at any scale. The second part confirmed the selective impact of warming, pointing out a potential evolutionary response to climate change in the future. The last part demonstrated and quantified the selective impact of multiple ECEs, which has not been demonstrated before. We call now for more studies assessing the selective impact of climate warming, which could allow to predict the evolutionary responses in the future.

Este trabalho busca entender a diversificação craniana dos macacos do Velho Mundo (Catarrhini) integrando duas abordagens para o estudo da evolução de caracteres complexos: a genética quantitativa e a integração morfológica. A investigação tem três objetivos principais: 1) comparar a magnitude e o padrão das relações entre os caracteres cranianos entre todos os Catarrhini; 2) testar a hipótese de que deriva genética é o único agente responsável pela diversificação craniana; 3) explorar as conseqüências evolutivas da associação entre caracteres. De posse de um banco de dados bastante representativo da diversidade dos macacos do Velho Mundo (39 medidas cranianas de cerca de 6.000 crânios de mais de 130 espécies), gerei as matrizes de correlação e de variância/covariância, que resumem as relações entre os caracteres, e comparei-as entre vários grupos. Comparei-as também a expectativas derivadas de modelos teóricos de evolução por deriva genética, além de simular a ação de seleção natural sobre essas matrizes para observar o comportamento evolutivo dos diversos padrões de associação entre caracteres. De maneira geral, o padrão das relações é o mesmo entre todos os Catarrhini, mas a magnitude com que os caracteres estão associados varia bastante. Isso tem conseqüências evolutivas importantíssimas, pois grupos com baixas magnitudes tendem a responder na mesma direção em que a seleção atua (alta flexibilidade evolutiva), enquanto que altas magnitudes estão associadas, independentemente da direção da seleção, a respostas ao longo do eixo de maior variação, que no caso dos Catarrhini corresponde à variação no tamanho (baixa flexibilidade evolutiva). A diversificação inicial do grupo parece ter sido gerada por seleção natural, mas nos níveis de gênero e espécie, deriva genética é o processo predominante; a exceção são os cercopitecíneos, onde há evidência de seleção também nesses níveis. Com base nesses resultados, proponho um modelo que associa a magnitude geral da correlação entre caracteres aos possíveis caminhos evolutivos que uma população pode seguir. Apesar de este trabalho estar empiricamente restrito aos macacos do Velho Mundo, esse modelo é válido para os mamíferos como um todo e pode ser testado em outros grupos, aumentando nossa compreensão de como a associação entre caracteres afeta a evolução dos seres vivos. / This is a study on the cranial diversification of the Catarrhini, a large group of primates that includes all Old World monkeys and apes, bringing together two approaches to investigate the evolution of complex characters: quantitative genetics and morphological integration. It has three main goals: 1) to compare magnitudes and patterns of inter-trait relationships in the skull among catarrhines; 2) to test the null hypothesis that genetic drift is the sole agent responsible for cranial diversification; 3) to explore the evolutionary consequences of inter-trait associations. With a large and representative cranial database of Old World monkeys and apes (39 measurements of around 6,000 skulls from more than 130 species), I generated and compared correlation and variance/covariance matrices, which summarize inter-trait relationships, among several Catarrhini groups. I compared some of those matrices to expectations derived from theoretical models of evolution through genetic drift, and simulated natural selection to observe the evolutionary behavior of each matrix. From a broad perspective, the patterns of relationships are the same among all catarrhines, but the magnitudes are quite variable. This has very important evolutionary consequences, because groups with low overall magnitudes tend to respond in the same direction of selection (high evolutionary flexibility), while higher magnitudes, regardless of the direction of selection, are associated to responses along the axis of highest variation, which in this case corresponds to size variation (low evolutionary flexibility). The initial diversification of catarrhines seems to have been generated by natural selection, but drift probably played a major role at the genus and species level; the exception are the cercopithecines, for which there is evidence for selection also in those levels. Based on these results, I propose a model that links the overall magnitude of inter-trait correlations to the possible evolutionary paths of a given population. This study is empirically restricted to Old World monkeys and apes, but the model has been proved valid to a broader sample of mammals and can be tested for other groups, contributing for our understanding of how complex characters evolve.

Bacterial resistance to antibiotics threatens modern healthcare on a global scale. Several actors in society, including the general public, must become more involved if this development is to be countered. The conveyance of relevant information provided through education and media reports is therefore of high concern. Antibiotic resistance evolves through the mechanisms of natural selection; in this way, a sound understanding of these mechanisms underlies explanations of causes and the development of effective risk-reduction measures. In addition to natural selection functioning as an explanatory framework to antibiotic resistance, bacterial resistance as a context seems to possess a number of qualities that make it suitable for teaching natural selection – a subject that has been proven notoriously hard to teach and learn. A recently suggested approach for learning natural selection involves so-called threshold concepts, which encompass abstract and integrative ideas. The threshold concepts associated with natural selection include, among others, the notions of randomness as well as vast spatial and temporal scales. Illustrating complex relationships between concepts on different levels of organization is one, of several, areas where visualizations are efficient. Given the often-imperceptible nature of threshold concepts as well as the fact that natural selection processes occur on different organizational levels, visual accounts of natural selection have many potential benefits for learning. Against this background, the present dissertation explores information conveyed to the public regarding antibiotic resistance and natural selection, as well as investigates how these topics are presented together, by scrutinizing media including news reports, websites, educational textbooks and online videos. The principal method employed in the media studies was content analysis, which was complemented with various other analytical procedures. Moreover, a classroom study was performed, in which novice pupils worked with a series of animations explaining the evolution of antibiotic resistance. Data from individual written assignments, group questions and video-recorded discussions were collected and analyzed to empirically explore the potential of antibiotic resistance as a context for learning about evolution through natural selection. Among the findings are that certain information, that is crucial for the public to know, about antibiotic resistance was conveyed to a low extent through wide-reaching news reporting. Moreover, explanations based on natural selection were rarely included in accounts of antibiotic resistance in any of the examined media. Thus, it is highly likely that a large proportion of the population is never exposed to explanations for resistance development during education or through newspapers. Furthermore, the few examples that were encountered in newspapers or textbooks were hardly ever visualized, but presented only in textual form. With regard to videos purporting to explain natural selection, it was found that a majority lacked accounts of central key concepts. Additionally, explanations of how variation originates on the DNA-level were especially scarce. These and other findings coming from the content analyses are discussed through the lens of scientific literacy and could be used to inform and strengthen teaching and scientific curricula with regards to both antibiotic resistance and evolution. Furthermore, several factors of interest for using antibiotic resistance in the teaching of evolution were identified from the classroom study. These involve, among others, how learners’ perception of threshold concepts such as randomness and levels of organization in space and time are affected by the bacterial context

O objetivo deste estudo foi compreender como seleção natural age sobre a variação fenotípica a fim de determinar como espécies respondem às mudanças ambientais. Para isso, usei esquilos do gênero Tamias (subgênero Neotamias, família Sciuridae) como um modelo em uma escala tanto macro quanto micro-evolutiva. Esse conjunto de 23 espécies de Neotamias é parte de uma radiação recente, ocupando uma ampla gama de hábitats com marcada partição de nicho entre as espécies. Um aspecto essencial que molda evolução fenotípica são características ambientais, tais como variações climáticas. Dessa forma, no primeiro capítulo eu examinei se as diferenças fenotípicas entre as espécies estão relacionadas às diferenças climáticas entre os hábitats que ocupam. Diversas características ambientais foram significativamente correlacionadas com atributos morfológicos, indicando que estas tiveram um papel importante como possíveis pressões seletivas conduzindo à divergência entre as espécies. Como consequência, é razoável supor que mudanças climáticas em tempo histórico (isto é, durante o Antropoceno) também afetam variação morfológica dentro de uma escala microevolutiva. No segundo capítulo, portanto, eu examinei esta expectativa usando espécimes de seis diferentes espécies, coletados com cerca de 100 gerações entre coletas (um século). Neste capítulo, não foi encontrada uma associação ente o grau de mudanças climáticas ao longo deste período e a magnitude de mudança morfológica ou de pressão seletiva. Contudo, as estimativas de força de seleção variaram substancialmente entre espécies: para a espécie Tamias alpinus observou-se uma alta estimativa de força de seleção, quase duas vezes maior do que para a espécie Tamias speciosus, a qual as menores forças de seleção foram observadas. Desta forma, a fim de avaliar o impacto de seleção direcional nos padrões de (co)variação fenotípica, no terceiro capítulo eu utilizei estas duas espécies, dado que representam extremos em termos de força de seleção dentre as populações analisadas. Estudos teóricos preveem que sob seleção direcional os padrões de (co)variação podem evoluir, realinhando-se com a paisagem adaptativa subjacente, aumentando a quantidade de variância genética na direção da seleção. Este padrão foi observado para T. alpinus, como esperado, dado que esta espécie sofreu a maior força de seleção. Além disso, para esta espécie foram observadas mudanças nos padrões de correlações entre os caracteres. Estes resultados apoiam expectativas obtidas a partir de modelos teóricos que consideram a evolução do mapa genótipo- fenótipo em resposta à seleção natural / The aim of this study was to understand how natural selection acts on phenotypic variation to determine species\' response to environmental change. I used chipmunks of the genus Tamias (subgenus Neotamias; family Sciuridae) as a model at both a macro and micro-evolutionary scales. This set of 23 species is part of a recent radiation that occupy a wide range of habitats with marked niche partitioning among co-distributed members. As climate variation is an essential aspect believed to shape phenotypic evolution, in the first chapter I examined how phenotypic differences among these species were related to climatic differences among the habitats occupied. Several climatic variables were significantly correlated with morphological attributes differentiating taxa, suggesting a possible causal link between climate, through selection, and species divergence. As a consequence, it is reasonable to suggest that climate change within historic times (the Anthropocene) has also affected cranial morphological variation within species at a microevolutionary scale. In the second chapter, therefore, I examined this expectation using specimens from six different species, each collected about 100 generations apart (one century). Here, no relationship was found between the degree of climate change over this period and the magnitude of observed morphological change, or in a measure of selection strength. Nevertheless, the estimates of selection strength varied substantially among these species: those for the alpine chipmunk (Tamias alpinus) were the strongest and nearly twice that of the co-distributed lodgepole chipmunk (Tamias speciosus). As a result, to assess the impact of directional selection on the observed patterns of phenotypic (co)variation, in the third chapter I contrasted these two species, since they represent the extremes in the estimated strength of selection among all the species\' populations I examined. Theory predicts that, under directional selection, patterns of phenotypic (co)variation might evolve in order to match the subjacent adaptive landscape. This prediction was upheld in the populations of alpine chipmunks, as perhaps expected since they exhibited the strong selective response. Equally importantly, I also observed changes in the overall correlation between traits for the alpine chipmunk in a pattern consistent with that expected under theoretical models that consider the evolution of the genotype-phenotype map in response to directional selection

As últimas décadas têm apresentado um crescente número de contribuições para o entendimento sobre quando e onde ocorreu o surgimento do Homo sapiens. Modelos baseados nessas evidências, geralmente, sugerem que a gênese dos humanos modernos ocorreu na África, há cerca de 200.000 anos antes do presente, de onde migraram para as outras partes do mundo. Análises da diversidade genética de populações atuais corroboram esse cenário, ao sugerir que, a partir de uma origem única, a espécie foi, gradativamente, perdendo variabilidade à medida que as populações divergiram, espacial e temporalmente, umas das outras e de suas ancestrais africanas. No que se refere especificamente à morfologia craniana, diversos autores sugerem a existência deste mesmo padrão de decréscimo da variabilidade em função do distanciamento em relação a África, embora seja, também, reconhecida entre os especialistas a partição da diversidade craniana humana entre dois padrões fundamentais: um representado pela morfologia similar àquela que caracterizou os primeiros Homo sapiens, antes que o processo de raciação, no sentido de diversificação, tivesse ocorrido, representado pela denominada \"morfologia generalizada\"; e outro representado pelas demais variações morfológicas, correspondendo às populações já diversificadas fora da África, denominada \"morfologia especializada\". Nesse sentido, o entendimento dos processos evolutivos envolvidos nos eventos de diferenciação morfológica gera bastante controvérsia entre os especialistas. Embora a maioria das informações já obtidas aponte para o fato de que a morfologia craniana evoluiu, majoritariamente, por processos estocásticos, algumas evidências sugerem que, ao menos em condições ambientais extremas, algumas regiões anatômicas cranianas específicas tenham uma parcela de sua variabilidade morfológica fixada por seleção natural. Nesse contexto, o objetivo primordial desta pesquisa é caracterizar a evolução da variação craniana humana, abordada a partir de dois tópicos centrais: 1) A investigação da composição, padrão de ocorrência, distribuição e estruturação da diversidade morfológica craniana humana; e, 2) A análise do contexto evolutivo da variação observada no crânio humano, em função de suas características de integração, modularidade e estase evolutiva investigadas a partir da exploração de seus padrões de variância e covariância. Para tanto, foram utilizadas as características métricas cranianas (24 variáveis do protocolo Howells) de 9.287 indivíduos, distribuídos em 161 populações autóctones de dispersão mundial. Apenas indivíduos morfologicamente íntegros constituíram o banco de dados, eliminando qualquer efeito devido à ocorrência de \"missing values\". Informações adicionais às séries presentes no banco de dados foram utilizadas para uma melhor caracterização geográfica e cronológica dessas populações, e que possibilitou o cálculo das distâncias geográficas entre elas e a estratificação dos dados sob diferentes critérios. Bancos de dados complementares, compostos por marcadores moleculares (mtDNA e microssatélites) também foram utilizados para a análise exploratória comparativa de questões específicas. Os resultados obtidos para as análises da composição, distribuição e estruturação da diversidade craniana humana mostram que grupos populacionais particulares, normalmente associados à alguma região geográfica específica, apresentam padrões de diversificação diversos daqueles observados para todas as populações analisadas de maneira conjunta, o que sugere a ocorrência de respostas evolutivas específicas associadas às condições particulares, como seleção, por exemplo. Em relação às investigações do contexto evolutivo da variação observada, inferida pelos padrões de correlação, covariância e modularidade investigados em diferentes agrupamentos populacionais, os resultados gerados demonstraram que, de maneira geral, os padrões de variância/covariância e a magnitude dos padrões de correlação entre os caracteres apresentam-se de maneira estável, com raras exceções ao estado de estase evolutiva predominante. Em suma, os resultados obtidos através das diferentes estratégias empregadas nesta tese reforçam a ideia de que a evolução da morfologia craniana é melhor explicada por um modelo que assuma a ocorrência de diferentes ditames evolutivos, como deriva genética e seleção natural, por exemplo, que, devido ao recente processo de diversificação da espécie apresentam, de maneira generalizada, em estado de estase / The last decades have seen a growing number of contributions to the understanding of when and where was the emergence of Homo sapiens. Models based on this evidence generally suggests that the genesis of modern humans occurred in Africa some 200,000 years before present, where migrated to other parts of the world. Analysis of genetic diversity of current populations corroborate this scenario, suggesting that, from a single source, the species was gradually losing variability as the populations diverged, spatially and temporally, from each other and from their African ancestors. With regard specifically to the cranial morphology, several authors suggest the existence of this same pattern of decreasing variability as a function of distance from Africa, although it is also recognized among experts partition the human cranial diversity between two fundamental patterns: one represented by morphology similar to that characterized the first Homo sapiens before the process raciação in the sense diversifying, occurred, represented by the so-called \"general morphology\" and the other represented by other morphological variations, corresponding to the populations already been diversified Africa, called \"specialized morphology.\" In this sense, understanding the evolutionary processes involved in the events of morphological differentiation generates a lot of controversy among experts. Although most of the information already obtained point to the fact that the cranial morphology evolved mostly by stochastic processes, some evidence suggests that, at least in extreme environmental conditions, some cranial specific anatomical regions have a portion of their morphological variability determined by natural selection. In this context, the primary objective of this research is to characterize the evolution of human cranial variation, approached from two themes: 1) The investigation of the composition, pattern of occurrence, distribution and structuring of human cranial morphological diversity, and, 2) analysis of the context of evolutionary change observed in the human skull, due to its characteristics of integration, modularity and evolutionary stasis investigated from the exploitation of their patterns of variance and covariance. For this, we used the metric cranial characteristics (24 variables protocol Howells) of 9287 individuals distributed in 161 indigenous peoples worldwide dispersion. Only morphologically intact individuals constituted the database, eliminating any effect due to the occurrence of \"missing values\". Additional information on these series in the database were used to better characterize geographic and chronological these populations, and that allowed the calculation of geographical distances between them and the stratification of the data under different criteria. Databases additional compounds by molecular markers (mtDNA and microsatellites) were also used for exploratory comparative analysis of specific issues. The results for the analyzes of the composition, structure and distribution of human cranial diversity show that particular population groups, usually associated with a specific geographic region, provide diversification patterns different from those observed for all populations analyzed jointly, suggesting the occurrence of specific evolutionary responses associated with particular conditions, such as selection, for example. Regarding investigations of evolutionary context of the variation observed, inferred by patterns of correlation, covariance and modularity investigated in different population groups, the results generated showed that, in general, the patterns of variance / covariance and magnitude of correlation patterns between characters are presented in a stable manner, with rare exceptions the state of evolutionary stasis predominant. In summary, the results obtained through the different strategies employed in this thesis reinforce the idea that the evolution of cranial morphology is best explained by a model that assumes the occurrence of different evolutionary dictates, as genetic drift and natural selection, for example, that due to the recent process of diversification of species present in a generalized way, in a state of stasis

O presente estudo aborda dois temas principais: a) história demográfica das populações nativas do continente americano e b) como a história demográfica e seletiva molda a diversidade e diferenciação dos genes HLA nessas populações. As populações ameríndias apresentam uma história evolutiva peculiar, com padrões demográficos distintos das outras populações do mundo. Estudos anteriores sugerem que elas possuem: a) baixa diversidade genética e alta diversidade inter-populacional em relação às demais populações do planeta; b) um gradiente de diminuição de diversidade no sentido norte-sul do continente americano; c) altos níveis de variabilidade intra-populacional e baixos níveis de variabilidade genética inter-populacional nas populações que vivem na região oeste da América do Sul, em comparação às populações do leste. Contudo, esses achados são baseados em estudos que apresentam uma deficiência amostral para populações ameríndias das terras do baixo rio Amazonas. No presente estudo nós suprimos essa deficiência ao analisar 11 populações das terras baixas do rio Amazonas e 3 populações do centro-sul do Brasil. Constatamos que: a) as populações do leste e oeste da América do Sul são altamente diferenciadas, corroborando estudos anteriores; b) a diferenciação entre as populações do leste da América do Sul é maior que entre as populações do oeste (região andina e noroeste da América do Sul) em acordo com estudos anteriores; c) a maior diferenciação entre as populações do leste da América do Sul é causada por grupos específicos (Arara do Iriri, Araweté, Surui e Ticuna Tarapaca), que apresentam histórias evolutivas peculiares; d) análises excluindo essas populações mostram que para o conjunto restante de populações, o nível de diferenciação das regiões do leste é similar ao encontrado para a diferenciação na região noroeste do continente sul americano; e) o leste da América do Sul é dividido em dois grupos populacionais distintos (oeste da Amazônia e leste da Amazônia/Centro-Sul do leste da América do Sul) e com diferente ancestralidade genética (o oeste da Amazônia com maior componente genético do Noroeste da América do Sul e o leste da Amazônia/Centro-Sul com maior componente Andino), em acordo com o modelo de rotas migratórias proposto por SCHMITZ, 1983 O perfil da variabilidade genética dos genes HLA nas populações nativas da América (com grande número de alelos e alguns com frequência muito distinta de outras regiões do mundo) diferem dos demais genes até então analisados nessas populações. Os genes HLA, localizados na região do MHC, estão envolvidos na resposta imune adaptativa e tem como função apresentar peptídeos na superfície celular. Diversos estudos mostram que os genes HLA estão evoluindo sob regime de seleção balanceadora. No presente estudo investigamos as contribuições da história demográfica e seletiva para moldar a variabilidade genética nas regiões adjacentes aos genes HLA em populações nativo-americanas. Para tanto, comparamos o perfil de 16 microssatélites na região do MHC com 61 microssatélites espalhados pelo genoma (controle demográfico) em 28 populações ameríndias, 1 africana e 1 europeia. Verificamos que: a) os microssatélites da região do MHC apresentam alto nível de desequilíbrio de ligação entre si; b) apresentam maior diferenciação inter-populacional do que os microssatélites espalhados pelo genoma. Este sinal é oposto ao que esperávamos verificar para genes evoluindo sob seleção balanceadora. Estudos anteriores mostram que mesmo populações que são compostas por conjuntos de alelos HLA distintos apresentam baixos níveis de diferenciação. Sugerimos que a seleção poderia estar favorecendo alelo (ou conjunto de alelos) específico em diferentes regiões geográficas, e que como os índices de diferenciação populacional como o FST estimam a variância das frequências alélicas, ele seria \"cego\" para a diferença na composição alélica das populações. Como estudo de caso analisamos o gene HLA-B, que, nas populações nativas da América, apresenta um conjunto composto por alelo endêmico e por alelos que ocorrem em alta frequência no continente americano e em baixa frequência fora dele. Com intuito de verificar se há sinais de seleção nas regiões adjacentes a este gene, analisamos seis microssatélites flanqueadores a ele em 28 populações nativas. Estimamos a heterozigose dos microssatélites associada a um determinado alelo de HLA-B bem como o grau de associação dos alelos de microssatélites com as linhagens e os alelos de HLA-B. As análises mostram que: a) de modo geral, a heterozigose associada aos alelos endêmicos é semelhante à observada em alelos cosmopolitas (com exceção dos alelos HLA-B*3909 e B*3543); b) a diferenciação observada a partir dos microssatélites adjacentes é maior entre as linhagens de HLA-B do que dentro das linhagens; c) haplótipos específicos de microssatélites apresentam forte associação com as linhagens de HLA-B. Esses resultados são surpreendentes visto que as linhagens de HLA-B já existiam antes mesmo da especiação humana. Sugerimos que a baixa heterozigose associada às linhagens pode estar relacionada a dois fatores: a) o gargalo populacional ocorrido durante a entrada do homem moderno no continente americano; b) seleção atuando no favorecimento não apenas os alelos mais também as linhagens de HLA-B. Desta forma concluímos que apesar da intensa história demográfica, as populações ameríndias apresentam sinais da atuação de forças seletivas na região do MHC / The present study addresses two main themes: a) demographic history of the Native American populations and b) how the demographic and selective history shapes the diversity and differentiation of the HLA genes on those populations. The Native American populations present a peculiar evolutive history, with demographic pattern that are distinct from other populations in the world. Previous studies suggest that they have: a) low genetic diversity and high inter-populational diversity compared to the other world populations; b) a diversity decreasing gradient on the north-south direction of the American continent; c) high levels of genetic variability between populations that live in the western South American region, compared with the eastern ones. However, these findings are based on studies that present a sampling deficiency for the Amerindian populations located on the Amazon River lowlands. On the present study we suppress this deficiency by analyzing 11 populations of the Amazon River lowlands and 3 populations of the Brazilian South-Center. We have observed that: a) the populations of the East and West of the South America are highly differentiated, in accordance with previous studies; b) the differentiation among the Eastern South America is greater than among the Western ones (Andean region and Northwestern South America) agreeing with previous studies; c) the larger differentiation among the Eastern South American populations is caused by specific groups (Ache, Arara do Iriri, Araweté, Suruí and Ticuna Tarapaca), which present peculiar evolutive histories; d) analysis that exclude these high differentiation level populations shows that for the remaining group, the differentiation level of the Eastern regions is similar to the differentiation levels found on the Western regions of the South American continent, corroborating the morphological studies; e) the east of the South America is divided in two distinct populational groups (Amazon Southwest and the Amazon East/South Central of South America) and with different genetic ancestry (the Amazon West with greater genetic component form the Northwestern South America and the Amazon East/South Central with greater Andean genetic component), agreeing with the migration routes model proposed by SCHMITZ, 1983. The HLA genes, located on the MHC region, are involved on the adaptative immune response and have the function of presenting peptides on the cellular surface. Various studies show that the HLA genes are evolving under balancing selection. The genetic variability profile of the HLA genes on the Native American populations (with great number of alleles and some with a frequency very distinct from other world regions) differs from the other genes so far analyzed in these population. On the present study we investigate the contributions of the demographic history on shaping the genetic variability of the regions adjacent to the HLA genes on Native-American populations. To accomplish that, we compared the profile of 16 microsatellites of the MHC region with 61 microsatellites spread through the genome (demographic control) in 28 Native American populations, 1 African population (Ovimbundu) and 1 European population (Portuguese). We observed that: a) the microsatellites of the MHC region present a high linkage disequilibrium among themselves, corroborating previous studies; b) present higher inter-populational differentiation than the microsatellites spread through the genome. This signal is opposed to the ones we expected from genes that are evolving under balancing selection. Previous studies show that even populations composed by groups of distinct HLA alleles present low levels of differentiation. We suggest that the selection could be favoring specific allele (or allele group) in different geographic regions, and since the populational differentiation indexes such as FST estimate the variance of the allelic frequencies, it would be \"blind\" to the difference on the allelic composition of the populations. As a case study, e investigate the HLA-B gene, which, in the American native populations, present a group composed by endemic allele and alleles that occur in high frequency on the American continent and in low frequency outside of it. With the intention of verifying if there are signs of selection on the regions adjacent to this gene, we have analyzes 6 microsatellites flanking to the HLA-B in 28 native populations. We estimated the heterozygosis of the microsatellites associated to a determined HLA-B allele as well as the degree of association of the microsatellite alleles with the HLA-B lineage and alleles. The analysis showed that: a) in general, the heterozygosis associated to the endemic alleles is similar to the one observed in cosmopolitan alleles (with exception of the HLA-B∗3909 and B∗3543); b) the differentiation observed from the adjacent microsatellites is greater between the HLA-B lineages than inside the lineages; c) specific microsatellites haplotypes present strong association with the HLA-B lineages. These results are surprising since the HLA-B lineages have existed even before the human speciation. We suggest that the low heterozygosis associated to the lineages could be related to two factors: a) the populational bottleneck occurred during the modern human entrence on the American continent; b)selection acting on the favoring, not only of the alleles, but also on the HLA-B lineages. In conclusion, despite the intense demographic history, the Native American populations present signs of selective forces acting on the MHC region

Positive natural selection leaves detectable, distinctive patterns in the genome in the form of a selective sweep. Identifying areas of the genome that have undergone selective sweeps is an area of high interest as it enables understanding of species and population evolution. Previous work has accomplished this by evaluating patterns within summary statistics computed across the genome and through application of machine learning techniques to raw population genomic data. When using raw population genomic data, convolutional neural networks have most recently been employed as they can handle large input arrays and maintain correlations among elements. Yet, such models often require massive amounts of training data and can be computationally expensive to train for a given problem. Instead, transfer learning has recently been used in the image analysis literature to improve machine learning models by learning the important features of images from large unrelated datasets beforehand, and then refining these models through subsequent application on smaller and more relevant datasets. We combine transfer learning with convolutional neural networks to improve classification of selective sweeps from raw population genomic data. We show that the combination of transfer learning with convolutional neural networks allows for accurate classification of selective sweeps. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2021. / FAU Electronic Theses and Dissertations Collection