With the transition from water to land in early tetrapods, and with transitions to secondarily aquatic habits in numerous tetrapod lineages, the functions of the vertebral column were transformed. Morphological changes in the vertebral column are a major mechanism by which vertebrates accommodate changes in locomotor forces. Although morphometric measurements from vertebrae have been correlated with axial mechanics and locomotor behaviour in numerous extant taxa, few studies have sought to test or apply these principles in non-mammalian tetrapods. In my thesis, I reconstructed the vertebral mechanics of fossil taxa that represent intermediate stages in water/land transitions of their lineages. Study taxa were the basal tetrapod Pederpes finneyae, which is one of the earliest known tetrapods to show indications of terrestrial adaptation, and three extinct crocodylomorphs, Terrestrisuchus, Protosuchus, and Pelagosaurus, which span the spectrum from fully terrestrial to primarily aquatic. I used a combination of morphometric measurements and 3D virtual models of bone morphology to estimate intervertebral joint stiffness and range of motion. For comparison, I also reconstructed the vertebral mechanics of four related extant taxa. Correlations between vertebral morphometrics and axial stiffness were statistically tested in (cadaveric) modem crocodylians, and I validated my methodology by comparing my results with data from extant taxa. My results reveal similarities and differences between the two lineages. Intervertebral joint compliance and range of motion tended to decrease with adaptation for terrestrial locomotion, as expected, but this trend seems to have reversed in later forms. Additionally, vertebral mechanics may have been largely controlled by different structural mechanisms in different lineages. The relationship between biomechanics of vertebrae and environment appears to be more complex than previously supposed. However, approaches that combine experimental measurements from extant animals, thorough analysis of fossil morphology, and explicit phylogenetic considerations have the potential to greatly improve locomotor reconstructions of extinct taxa.

Jawed vertebrates (gnathostomes) account for over 99% of living vertebrate diversity, with origins that stretch back nearly half a billion years, and comprise two groups: Osteichthyes (fishes and land-dwelling vertebrates) and Chondrichthyes (sharks, rays and chimaeras). Osteichthyans are the dominant clade, with at least 60,000 species approximately evenly divided between two clades: the Actinopterygii and the Sarcopterygii. However, our understanding of early osteichthyan evolution is skewed in favour of sarcopterygians, leaving the origin of nearly half of all vertebrate diversity critically understudied. Furthermore, recent upheavals in the early gnathostome tree have destabilised relationships amongst fossil taxa and eroded our understanding of primitive anatomical conditions of key groups. Central to understanding early gnathostome evolution is the braincase, an anatomically complex structure that provides a wealth of morphological characters. However, braincases rarely fossilise, and their position inside the skull makes them difficult to attain. X-ray tomography allows a comprehensive description of the internal and external anatomy of fossils, including the braincase. This thesis sets out to target phylogenetically pivotal taxa and incorporate new anatomical data in building up a picture of character evolution in early jawed vertebrates. In particular, I target the gnathostome stem, describing a new taxon that helps bridge the morphological gap between placoderms and crown gnathostomes, allowing a more comprehensive understanding of both dermal and endoskeletal evolution. I also focus on early actinopterygians, describing the endoskeleton of the first members of the group in order to understand primitive anatomical conditions. I then investigate actinopterygian braincase anatomy in the context of a revised phylogenetic analysis, illuminating the early evolution of the actinopterygians. Finally, I present a synthetic review of braincase anatomy across the early gnathostome tree. These results provide a more accurate picture of braincase evolution across gnathostomes and actinopterygians, clarifying our understanding of their evolution while revealing new information about when key innovations arose in the brains of the very first ray-finned fishes.

The human prefrontal cortex (PFC) is associated with complex cognitive behaviors such as planning for the future, memory for serial order, social information processing and language. Understanding how the PFC has changed through time is central to the study of human neural evolution. Here we investigate the expansion of the PFC by measuring relative surface area of the PFC in Pan troglodytes and Homo sapiens. Magnetic resonance images (MRI's) from 8 preserved chimpanzee brains (3 male and 5 female adults) were segmented and measured. The results of this study indicate that there are gross anatomical differences between the chimpanzee and human prefrontal cortex beyond absolute size. The lower surface area to volume ratio in PFC of the chimpanzee when compared to a human indicates less gyral white matter in this region and thus, less associative connectivity. This anatomical evidence of a difference corresponds with the lesser cognitive complexity observed in chimpanzees. / by Ian D. George. / Thesis (M.A.)--Florida Atlantic University, 2009. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2009. Mode of access: World Wide Web.

Orientador: Cesar Martins / Coorientador: Ney Lemke / Banca: Antonio Sérgio Kimus Braz / Banca: José Luiz Rybarczyk Filho / Banca: Reinaldo Otávio Alvarenga Alves de Brito / Banca: Pedro Manuel Galetti Junior / Resumo: Atualmente os sistemas biológicos vem sendo abordados por diversas áreas de pesquisas, dentre elas a biologia de sistemas. Essa área tem centrado esforços para descrever e compreender as relações entre os componentes bióticos e abióticos desses sistemas, utilizando para isso a teoria de grafos. Uma forma de estudar esses sistemas, é avaliar as interações entre proteínas, que são as interações biomoleculares mais abundantes nas células. Nesse contexto, a presente tese focou no desenvolvimento de um algoritmo computacional capaz de predizer interações entre proteínas de qualquer espécie ou conjunto protéico. Para isso, foram utilizadas técnicas de aprendizado de máquina (sub-área da inteligência artificial) para a construção e aplicação desse preditor, o qual mostrou-se eficaz em predizer interações entre proteínas de mais de 80 espécies diferentes, incluindo interações entre proteínas de parasita e hospedeiro. Esse novo preditor foi aplicado no proteoma de zebrafish (Danio rerio) e humanos (Homo sapiens), gerando assim redes de interações proteicas para ambas as espécies. As interações obtidas foram avaliadas em um contexto geral e o foco das análises foi direcionado para a sub-rede relacionada com as vias de determinação e diferenciação sexual em vertebrados. Os resultados demonstraram uma relativa baixa conservação desses grafos ao longo da evolução dos vertebrados, tanto do ponto de vista global quanto da sub-rede relacionada com a determinação e diferenciação sexual em vertebrados. Além disso, foi possível observar ao menos um hub conservado entre as duas sub-redes, o qual representa um novo alvo a ser avaliado por pesquisas experimentais. Contudo, os dados demonstram que o preditor gerado possui um grande potencial para diversas áreas de estudos e é bastante útil para predição de interações em larga-escala. Além disso, os aspectos evolutivos aqui ... / Abstract: Nowadays the biological systems have been analyzed under several research foci, including the system biology. This area focus to describe and understand the relationship between biotic and abiotic factors using the graph theory. The protein interactions are target interactions to the system biology because they are the most abundant biomolecular interactions within a cell. Thus, this thesis reported the development of a computational algorithm to predict proteinprotein interactions for all species or protein sets. The machine learning technique (sub-area of artificial intelligence) were used to develop and apply this method, giving effective results to predict protein-protein interaction for more than 80 different species, including parasitehost associations. This new predictor was applied to the proteome set of zebrafish (Danio rerio) and humans (Homo sapiens), generating the protein-protein interactions for both species. Evolutionary aspects of the protein interactions were studied in a broad context and the focus was directed to the sub-network involved in the vertebrate sex determination and differentiation. The results reported a low conservation of those graphs across the evolution in a general view or for the sub-network related to the vertebrate sex determination and differentiation. Moreover, it was reported at least one conserved hub between both subnetworks, to be further evaluated by experimental procedures. Anyway, the data showed that the predictor here reported may be very useful for several research areas and it is desirable for large-scale prediction procedures. Furthermore, the evolutionary aspects discussed in this thesis open new perspectives concerning system biology and evolutionary pathways of vertebrate sex determination and differentiation / Doutor

Made available in DSpace on 2014-06-11T19:32:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-21Bitstream added on 2014-06-13T21:03:46Z : No. of bitstreams: 1 000741895.pdf: 15459081 bytes, checksum: d63bdd273032427c5d062ded87237abe (MD5) / Atualmente os sistemas biológicos vem sendo abordados por diversas áreas de pesquisas, dentre elas a biologia de sistemas. Essa área tem centrado esforços para descrever e compreender as relações entre os componentes bióticos e abióticos desses sistemas, utilizando para isso a teoria de grafos. Uma forma de estudar esses sistemas, é avaliar as interações entre proteínas, que são as interações biomoleculares mais abundantes nas células. Nesse contexto, a presente tese focou no desenvolvimento de um algoritmo computacional capaz de predizer interações entre proteínas de qualquer espécie ou conjunto protéico. Para isso, foram utilizadas técnicas de aprendizado de máquina (sub-área da inteligência artificial) para a construção e aplicação desse preditor, o qual mostrou-se eficaz em predizer interações entre proteínas de mais de 80 espécies diferentes, incluindo interações entre proteínas de parasita e hospedeiro. Esse novo preditor foi aplicado no proteoma de zebrafish (Danio rerio) e humanos (Homo sapiens), gerando assim redes de interações proteicas para ambas as espécies. As interações obtidas foram avaliadas em um contexto geral e o foco das análises foi direcionado para a sub-rede relacionada com as vias de determinação e diferenciação sexual em vertebrados. Os resultados demonstraram uma relativa baixa conservação desses grafos ao longo da evolução dos vertebrados, tanto do ponto de vista global quanto da sub-rede relacionada com a determinação e diferenciação sexual em vertebrados. Além disso, foi possível observar ao menos um hub conservado entre as duas sub-redes, o qual representa um novo alvo a ser avaliado por pesquisas experimentais. Contudo, os dados demonstram que o preditor gerado possui um grande potencial para diversas áreas de estudos e é bastante útil para predição de interações em larga-escala. Além disso, os aspectos evolutivos aqui... / Nowadays the biological systems have been analyzed under several research foci, including the system biology. This area focus to describe and understand the relationship between biotic and abiotic factors using the graph theory. The protein interactions are target interactions to the system biology because they are the most abundant biomolecular interactions within a cell. Thus, this thesis reported the development of a computational algorithm to predict proteinprotein interactions for all species or protein sets. The machine learning technique (sub-area of artificial intelligence) were used to develop and apply this method, giving effective results to predict protein-protein interaction for more than 80 different species, including parasitehost associations. This new predictor was applied to the proteome set of zebrafish (Danio rerio) and humans (Homo sapiens), generating the protein-protein interactions for both species. Evolutionary aspects of the protein interactions were studied in a broad context and the focus was directed to the sub-network involved in the vertebrate sex determination and differentiation. The results reported a low conservation of those graphs across the evolution in a general view or for the sub-network related to the vertebrate sex determination and differentiation. Moreover, it was reported at least one conserved hub between both subnetworks, to be further evaluated by experimental procedures. Anyway, the data showed that the predictor here reported may be very useful for several research areas and it is desirable for large-scale prediction procedures. Furthermore, the evolutionary aspects discussed in this thesis open new perspectives concerning system biology and evolutionary pathways of vertebrate sex determination and differentiation

Orientadores: Lucia Elvira Alvares, Jose Xavier Neto / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-13T10:17:43Z (GMT). No. of bitstreams: 1 Sobreira_DeboraRodrigues_M.pdf: 2481929 bytes, checksum: 2cb1105ccc78322b5f11f4528108d2fc (MD5) Previous issue date: 2009 / Resumo: Splicing Alternativo é um mecanismo importante para expandir a diversidade protéica em eucariotos. Este processo permite a produção de diferentes mRNAs a partir de uma mesma molécula de pré-RNA e é freqüentemente utilizado pelos genes envolvidos no desenvolvimento embrionário. O gene Oapper1 (Opr1) é um importante modulador da via de sinalização Wnt, atuando em diversos processos como especificação do tecido neural, morfogênese cefálica e desenvolvimento do coração e olho. Entre seus parceiros estão as '1lOléculas Dishevelled, o fator de transcrição TCF-3 (ambas as moléculas envolvidas na sinalização Wnt) e Dbf-4 (regulador do ciclo celular). Considerando que Dpr1 possui uma estrutura modular e interage com diferentes parceiros moleculares através de diferentes domínios estruturais, esta molécula poderia utilizar a maquinaria de Splicing Alternativo para combinar diferentes domínios e conseqüentemente ampliar suas funções biológicas. Neste estudo, descrevemos uma nova Variante do gene Opr1, identificada inicialmente no transcriptoma de camundongo utilizando ferramentas de Bioinformática. Esta nova Variante é maior em 111 pb em relação à codificada pela seqüência referência de RNAm para Dpr1 RefSeq, as quais são denominadas, respectivamente, como Variante A e Variante B. Estes transcritos variantes são gerados por dois sítios aceptores de Splicing distintos presentes no início do exon 4. O segmento exclusivo da Variante A codifica 37 aminoácidos localizados na região onde Opr1 se associa ao fator transcricional TCF-3. Uma análise comparativa do lócus de Opr1 entre diversos vertebrados (peixe, anfíbio, galinha, camundongo e humano) revelou que ambos os sítios aceptores de Splicing são conservados nos tetrápodas, enquanto que em peixe apenas um sítio é encontrado. Ensaios de RT-PCR confirmaram nossos resultados obtidos em Bioinformática. Além disso, demonstramos que ambas as Variantes são co-expressas ao longo do desenvolvimento de galinha, sugerindo que a concentração relativa dessas moléculas pode ser importante para a sua função. Finalmente, análises de pressão seletiva foram realizadas para a molécula de Dpr1. Apesar de não se confirmar a presença de seleção positiva ao longo da proteína Dpr1, o exon 4 parece estar sob pressão seletiva mais relaxada quando comparado aos outros exons. Nossos resultados são consistentes com a hipótese de que o mecanismo de Splicing Alternativo atua acelerando a evolução, reduzindo a seleção negativa. / Abstract: Alternative splicing is an important mechanism to expand protein diversity in eukaryotes. This process allows the production of different mRNAs from a single coding sequence and is frequentfy used by genes involved in development. Oapper 1 (Opr1) is an important rnodulator of Wnt signalling, working in several developmental processes, such as neural tissue specification, head morphogenesis, heart and eye development. While its interaction with Oishevelled is known to modulate Wnt signalling both in vivo and in vitre, the interaction wrth other molecules is required to mediate its multiple biological functions. Considering that Dpr1 has a modular structure that mediates its interaction with different partners through different structural domains, this molecule could greatly benefit from alternative splicing in order to combine different domains and consequently amplify its biological functions. In the present study we describe a new Opr1 isoform that was initially identified in the mouse transcriptome using bioinformatic tools. This isoform is 111 pb longer than the one encoded by the RefSeq mRNA for Opr1, here named O and E isoforms, respectively. The variant transcripts are generated through two distinct acceptor splice sites in exon 4. The segment exclusive of the O isoform is in frame and encodes 37 residues located in a variable region of Oprl exon 4, known to be necessary for the interaction with the transcriptional factor Tcf3. comparative analysis of the Opr1 locus among fish, frog, chicken, mouse and human revealed that in tetrapods two acceptor splice sites are conserved in the beginning of the exon 4, while in fish a single acceptor splice site is found. RT-PCR using species-specific primers confirmed the expression of the O and E isoforms in tetrapods while in fish only the O isoform was detected. In addition, we showed that the Opr1 isoforms are coexpressed throughout chicken development, suggesting that the relative concentration of these molecules may be important for their functionality. Finally, even though no evidence of positive selection was detected for the entire Dpr1 protein, exon 4 seems to be under more relaxed selective pressure than the other exons. These results are consistent with the notion that alternative splicing can act as a mechanism for opening accelerated paths of evolution by reducing negative selection pressure. / Mestrado / Histologia / Mestre em Biologia Celular e Estrutural

The Diadectomorpha is a central taxon in understanding the origin and early evolution of amniotes. It is considered a sister taxon to Amniota and is so similar to amniotes that some researchers have placed it within the Amniota itself. This group is composed of three families: the Limnoscelidae, the Tseajaiidae, and the Diadectidae. Being the most basal member of this group, the family Limnoscelidae is especially important in these studies.

The cranial anatomy of the basal captorhinid reptile Captorhinikos parvus (Reptilia, Captorhinidae), is reinterpreted here based on analysis of a group of new specimens recovered subsequent to its original diagnosis as well as further analysis of the original specimens utilized in E.C. Olson's original characterization of the species. Structural features inconsistent with the generic description suggest the redefinition of C. parvus as a new genus, Rhodotheratus parvus. Analyses of basal members and selected derived members support the characterization of Rhodotheratus as a distinct taxon.

L’acquisition de données génomiques ne cesse de croître, ainsi que l’appétit pour les interpréter. Mais déterminer les processus qui ont façonné l’évolution des séquences codantes (et leur importance relative) est un défi scientifique passant par le développement de modèles statistiques de l’évolution prenant en compte de plus en plus d’hétérogénéités au niveau des processus mutationnels et de sélection. Identifier la sélection est une tâche qui nécessite typiquement de détecter un écart entre deux modèles : un modèle nulle ne permettant pas de régime évolutif adaptatif et un modèle alternatif qui lui en permet. Lorsqu’un test entre ces deux modèles rejette le modèle nulle, on considère avoir détecter la présence d’évolution adaptative. La tâche est d’autant plus difficile que le signal est faible et confondu avec diverses hétérogénéités négligées par les modèles. La détection de la sélection sur l’usage des codons spécifiquement est controversée, particulièrement chez les Vertébrés. Plusieurs raisons peuvent expliquer cette controverse : (1) il y a un biais sociologique à voir la sélection comme moteur principal de l’évolution, à un tel point que les hétérogénéités relatives aux processus de mutation sont historiquement négligées ; (2) selon les principes de la génétique des populations, la petite taille efficace des populations des Vertébrés limite le pouvoir de la sélection sur les mutations synonymes conférant elles-mêmes un avantage minime ; (3) par contre, la sélection sur l’usage des codons pourrait être très localisée le long des séquences codantes, à des sites précis, relevant de contraintes de sélection relatives à des motifs utilisés par la machinerie d’épissage, par exemple. Les modèles phylogénétiques de type mutation-sélection sont les outils de prédilection pour aborder ces questions, puisqu’ils modélisent explicitement les processus mutationnels ainsi que les contraintes de sélection. Toutes les hétérogénéités négligées par les modèles mutation-sélection de Yang and Nielsen [2008] peuvent engendrer de faux positifs allant de 20% (préférence site-spécifique en acides aminés) à 100% (hypermutabilité des transitions en contexte CpG) [Laurin-Lemay et al., 2018b]. En particulier, l’hypermutabilité des transitions du contexte CpG peut à elle seule expliquer la sélection détectée par Yang and Nielsen [2008] sur l’usage des codons. Mais, modéliser des phénomènes qui prennent en compte des interdépendances dans les données (par exemple l’hypermutabilité du contexte CpG) augmente de beaucoup la complexité des fonctions de vraisemblance. D’autre part, aujourd’hui le niveau de sophistication des modèles fait en sorte que des vecteurs de paramètres de haute dimensionnalité sont nécessaires pour modéliser l’hétérogénéité des processus étudiés, dans notre cas de contraintes de sélection sur la protéine. Le calcul bayésien approché (Approximate Bayesian Computation ou ABC) permet de contourner le calcul de la vraisemblance. Cette approche diffère de l’échantillonnage par Monte Carlo par chaîne de Markov (MCMC) communément utilisé pour faire l’approximation de la distribution a posteriori. Nous avons exploré l’idée de combiner ces approches pour une problématique spécifique impliquant des paramètres de haute dimensionnalité et de nouveaux paramètres prenant en compte des dépendances entre sites. Dans certaines conditions, lorsque les paramètres de haute dimensionnalité sont faiblement corrélés aux nouveaux paramètres d’intérêt, il est possible d’inférer ces mêmes paramètres de haute dimensionnalité avec la méthode MCMC, et puis les paramètres d’intérêt au moyen de l’ABC. Cette nouvelle approche se nomme CABC [Laurin-Lemay et al., 2018a], pour calcul bayésien approché conditionnel (Conditional Approximate Bayesian Computation : CABC). Nous avons pu vérifier l’efficacité de la méthode CABC en étudiant un cas d’école, soit celui de l’hypermutabilité des transitions en contexte CpG chez les Eutheria [Laurin-Lemay et al., 2018a]. Nous trouvons que 100% des 137 gènes testés possèdent une hypermutabilité des transitions significative. Nous avons aussi montré que les modèles incorporant l’hypermutabilité des transitions en contexte CpG prédisent un usage des codons plus proche de celui des gènes étudiés. Ceci suggère qu’une partie importante de l’usage des codons peut être expliquée à elle seule par les processus mutationnels et non pas par la sélection. Finalement nous explorons plusieurs pistes de recherche suivant nos développements méthodologiques : l’application de la détection de l’hypermutabilité des transitions en contexte CpG à l’échelle des Vertébrés ; l’expansion du modèle pour reconnaître des contextes autres que seul le CpG (e.g., hypermutabilité des transitions et transversions en contexte CpG et TpA) ; ainsi que des perspectives méthodologiques d’amélioration de la performance du CABC. / The acquisition of genomic data continues to grow, as does the appetite to interpret them. But determining the processes that shaped the evolution of coding sequences (and their relative importance) is a scientific challenge that requires the development of statistical models of evolution that increasingly take into account heterogeneities in mutation and selection processes. Identifying selection is a task that typically requires comparing two models: a null model that does not allow for an adaptive evolutionary regime and an alternative model that allows it. When a test between these two models rejects the null, we consider to have detected the presence of adaptive evolution. The task is all the more difficult as the signal is weak and confounded with various heterogeneities neglected by the models. The detection of selection on codon usage is controversial, particularly in Vertebrates. There are several reasons for this controversy: (1) there is a sociological bias in seeing selection as the main driver of evolution, to such an extent that heterogeneities relating to mutation processes are historically neglected; (2) according to the principles of population genetics, the small effective size of vertebrate populations limits the power of selection over synonymous mutations conferring a minimal advantage; (3) On the other hand, selection on the use of codons could be very localized along the coding sequences, at specific sites, subject to selective constraints related to DNA patterns used by the splicing machinery, for example. Phylogenetic mutation-selection models are the preferred tools to address these issues, as they explicitly model mutation processes and selective constraints. All the heterogeneities neglected by the mutation-selection models of Yang and Nielsen [2008] can generate false positives, ranging from 20% (site-specific amino acid preference) to 100% (hypermutability of transitions in CpG context)[Laurin-Lemay et al., 2018b]. In particular, the hypermutability of transitions in the CpG context alone can explain the selection on codon usage detected by Yang and Nielsen [2008]. However, modelling phenomena that take into account data interdependencies (e.g., hypermutability of the CpG context) greatly increases the complexity of the likelihood function. On the other hand, today’s sophisticated models require high-dimensional parameter vectors to model the heterogeneity of the processes studied, in our case selective constraints on the protein. Approximate Bayesian Computation (ABC) is used to bypass the calculation of the likelihood function. This approach differs from the Markov Chain Monte Carlo (MCMC) sampling commonly used to approximate the posterior distribution. We explored the idea of combining these approaches for a specific problem involving high-dimensional parameters and new parameters taking into account dependencies between sites. Under certain conditions, when the high dimensionality parameters are weakly correlated to the new parameters of interest, it is possible to infer the high dimensionality parameters with the MCMC method, and then the parameters of interest using the ABC. This new approach is called Conditional Approximate Bayesian Computation (CABC) [Laurin-Lemay et al., 2018a]. We were able to verify the effectiveness of the CABC method in a case study, namely the hypermutability of transitions in the CpG context within Eutheria [Laurin-Lemay et al.,2018a]. We find that 100% of the 137 genes tested have significant hypermutability of transitions. We have also shown that models incorporating hypermutability of transitions in CpG contexts predict a codon usage closer to that of the genes studied. This suggests that a significant part of codon usage can be explained by mutational processes alone. Finally, we explore several avenues of research emanating from our methodological developments: the application of hypermutability detection of transitions in CpG contexts to the Vertebrate scale; the expansion of the model to recognize contexts other than only CpG (e.g., hypermutability of transitions and transversions in CpG and TpA context); and methodological perspectives to improve the performance of the CABC approach.