No description available.

The variation of genome content and structure across the tree of life is astounding and can provide clues to understand the process of evolution. Overall, this helps us understand the history of life and how organisms have fundamentally changed and adapted to their environments. Gene duplication is an important mechanism for molecular evolution because it provides opportunity for functional novelty and molecular innovation. Gene duplication creates new functional gene copies with different selective pressures that allow them to take on new or specialized functions. Throughout this work, I explored the interplay between genetic changes, molecular phenotype, and the selection of duplicate gene copies. I particularly focused on the genetic opportunity, consequences, and selective pressures of the mechanisms for short-term and long-term duplicate copy retention. I modeled the stochastic processes of mutation and selection and their effect on duplicate gene copy retention. Specifically, I modeled the interplay between subfunctionalization and dosage balance and found that selection may cause genes that are sensitive to dosage balance effects to experience delayed subfunctionalization, but ultimately lead to higher levels of subfunctionalization. These findings suggest that subfunctionalization may not occur as a purely neutral process. Next, I used survival analysis methods to model patterns of duplicate gene retention in genomes experiencing consecutive whole genome duplication events. I modeled three hypotheses to explain patterns of duplicate gene retention including the Independence Hypothesis, the Gene Duplicability Hypothesis, and a novel Mutational Opportunity Hypothesis. Under the Gene Duplicability and Mutational Opportunity hypotheses, the expected patterns of duplicate gene retention after consecutive whole genome duplication events are greatly affected by the ages of the whole genome duplication events and the functional properties of the genomic content that influence opportunity and selection. Additionally, I describe how statistical model testing techniques can be applied to investigate which hypothesis is consistent with patterns of retention in real-world phylogenetic datasets. I used these described techniques to explore the hypotheses’ parameter space consistent with a modest dataset of fish and plant lineages. These results suggest that a gene duplicate’s retention after whole genome duplication events may be influenced by its functional properties. Key findings underscore the multifaceted nature of duplicate gene retention, influenced by a myriad of factors including genetic opportunity, selective pressures, and evolutionary context. By dissecting the underlying mechanisms driving duplicate gene retention, this dissertation advances our understanding of the evolutionary dynamics shaping genome evolution and functional diversity across diverse biological systems. / Biology

Les gènes, qui servent à encoder les fonctions biologiques des êtres vivants, forment l'unité moléculaire de base de l'hérédité. Afin d'expliquer la diversité des espèces que l'on peut observer aujourd'hui, il est essentiel de comprendre comment les gènes évoluent. Pour ce faire, on doit recréer le passé en inférant leur phylogénie, c'est-à-dire un arbre de gènes qui représente les liens de parenté des régions codantes des vivants. Les méthodes classiques d'inférence phylogénétique ont été élaborées principalement pour construire des arbres d'espèces et ne se basent que sur les séquences d'ADN. Les gènes sont toutefois riches en information, et on commence à peine à voir apparaître des méthodes de reconstruction qui utilisent leurs propriétés spécifiques. Notamment, l'histoire d'une famille de gènes en terme de duplications et de pertes, obtenue par la réconciliation d'un arbre de gènes avec un arbre d'espèces, peut nous permettre de détecter des faiblesses au sein d'un arbre et de l'améliorer. Dans cette thèse, la réconciliation est appliquée à la construction et la correction d'arbres de gènes sous trois angles différents: 1) Nous abordons la problématique de résoudre un arbre de gènes non-binaire. En particulier, nous présentons un algorithme en temps linéaire qui résout une polytomie en se basant sur la réconciliation. 2) Nous proposons une nouvelle approche de correction d'arbres de gènes par les relations d'orthologie et paralogie. Des algorithmes en temps polynomial sont présentés pour les problèmes suivants: corriger un arbre de gènes afin qu'il contienne un ensemble d'orthologues donné, et valider un ensemble de relations partielles d'orthologie et paralogie. 3) Nous montrons comment la réconciliation peut servir à "combiner'' plusieurs arbres de gènes. Plus précisément, nous étudions le problème de choisir un superarbre de gènes selon son coût de réconciliation. / Genes encode the biological functions of all living organisms and are the basic molecular units of heredity. In order to explain the diversity of species that can be observed today, it is essential to understand how genes evolve. To do this, the past has to be recreated by inferring their phylogeny, i.e. a gene tree depicting the parental relationships between the coding regions of living beings. Traditional phylogenetic inference methods have been developed primarily to construct species trees and are solely based on DNA sequences. Genes, however, are rich in information and only a few known reconstruction methods make usage of their specific properties. In particular, the history of a gene family in terms of duplications and losses, obtained by the reconciliation of a gene tree with a tree species, may allow us to detect weaknesses in a tree and improve it. In this thesis, reconciliation is applied to the construction and correction of gene trees from three different angles: 1) We address the problem of resolving a non-binary gene tree. In particular, we present a linear time algorithm that solves a polytomy based on reconciliation. 2) We propose a new gene tree correction approach based on orthology and paralogy relations. Polynomial-time algorithms are presented for the following problems: modify a gene tree so that it contains a given set of orthologous genes, and validate a set of partial orthology and paralogy relations. 3) We show how reconciliation can be used to "combine'' multiple gene trees. Specifically, we study the problem of choosing a gene supertree based on its reconciliation cost.

The duplication of genes followed by selection is perhaps the most prominent way in which molecular biological systems gain multiplicity, diversity and functional complexity in evolution. Whole genome duplications (WGDs) therefore have the potential of generating an extraordinary amount of evolutionary innovation. It is now accepted that the vertebrate lineage has gone through two rounds of WGD in its early stages, after the divergence of invertebrate chordates and before the emergence of jawed vertebrates. These basal vertebrate WGDs are called 2R for two rounds of whole genome duplication. An additional WGD called 3R occurred early in the evolution of teleost fishes, before the radiation of this species-rich group. This thesis describes the evolution of several endocrine and neuronal gene families in relation to the vertebrate WGDs, through a comparative genomic approach including both phylogenetic analyses and chromosomal location data across a wide range of vertebrate taxa. These results show that numerous endocrine gene families have expanded in 2R and in several cases also in 3R. These include the gene families of oxytocin and vasopressin receptors (OT/VP-R), somatostatin receptors (SSTR) and insulin-like growth factor binding proteins (IGFBP). For the OT/VP-R and SSTR families, previously undescribed subtypes were identified. The protein hormone family that includes growth hormone (GH), prolactin (PRL) and somatolactin (SL) acquired a new PRL gene in 2R, however the origins of GH, PRL and SL likely predate 2R. The corresponding family of receptors diversified during different time periods through a combination of local duplications and 3R. Neuronal gene families of the visual system have also expanded in 2R and 3R. The results presented here demonstrate that the vertebrate repertoire of visual opsin genes arose in 2R as part of chromosomal blocks that also include the OT/VP-R genes. The gene families including the transducin alpha, beta and gamma subunits also arose in 2R, hinting at the importance of these events in the diversification and specialization of phototransduction cascades for rods and cones. Thus, the whole genome duplications have been important contributors to the evolution of both vision and endocrine regulation in the vertebrates.

Thesis (MComm)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: PEP is a devision of Pepkor Retail Limited and is the biggest single brand store network in Southern Africa and also owns and runs the largest clothing factory in Southern Africa. It was founded in 1965 and has since grown to more than 1 400 stores in 9 African countries (there is a PEP store in almost every town and village in South Africa). Currently the warehouse management system (WMS) implemented by PEP only allows for a stock keeping unit (SKU) to be placed on one picking line in one location when the distribution list (DBN) is released. Because pickers are only allowed to walk clockwise around the conveyor belt, they are forced to pass a location at least the same number of times as the number of branches to which the SKU is to be distributed to. Therefore if the SKUs with the highest pick frequency can be assigned to 2 locations (it is duplicating the SKU), the number of times each of these locations must be passed may be reduced. In this study 4 questions are considered when 15 algorithms are constructed that will determine how an algorithm assign the SKUs to picking lines. Question 1 determines whether the original picking lines are to be treated separately (PS) or to combine them rst (PC). The second question is to decide if the SKUs are rst to be duplicated and then assigned to picking lines (DA) or if they are rst assigned to picking lines and then duplicated (AD). Question 3 determines whether the non-duplicate and duplicate SKUs are treated separately (ND) or simultaneously (S) when they are assigned to the picking lines. The nal question is to specify how the SKUs are assigned to the picking lines. Three assignment methods (cyclical, set length subset sequential assignment, remaining high, low cyclical assignment) and 6 clustering algorithms are introduced. The conclusion is made that the SKUs with the highest pick frequency is duplicated rst to yield the biggest saving in the number of cycles. Between 40{70% of the SKUs should be duplicated, dependant on the algorithm used. The only decision that has a major in uence on the number of cycles is the assignment method used. Algorithm 5 and 8 yielded the greatest saving in the number of cycles (40.7% and 39.8% respectively), both implementing set length subset sequential assignment, followed by the clustering algorithms. / AFRIKAANSE OPSOMMING: PEP is 'n afdeling van Pepkor Retail Limited en is die grootste enkel-handelsmerk winkelnetwerk in Suidelike Afrika. PEP besit en bestuur ook die grootste klerefabriek in Suidelike Afrika. PEP is gestig in 1965 en het sedertien gegroei tot meer as 1 400 winkels in 9 Afrika lande (daar is 'n PEP winkel in amper elke dorp in Suid-Afrika). Op die oomblik laat die pakhuisbestuurstelsel, wat deur PEP in sy distribusie sentrum ge mplementeer word, slegs toe dat voorraadeenhede (VEs) in 'n enkele vakkie langs 'n enkele uitsoeklyn geplaas word. Aangesien werkers slegs toegelaat word om kloksgewys om die vervoerband te beweeg, word hulle gedwing om ten minste soveel keer verby elke vakkie in die uitsoeklyn te loop as wat die aantal winkels is waarna die VEs in daardie vakkie versprei moet word. Dus indien die vakkies wat die VEs bevat wat na die meeste winkels versprei moet word, tussen 2 vakkies verdeel word (die VE word gedupliseer), verminder die aantal kere wat beide vakkies besoek moet word. In hierdie studie word 4 vrae beskou wat geantwoord moet word wanneer die 15 algoritmes opgestel word, wat sal bepaal hoe die algoritme die VEs hanteer. Vraag 1 bepaal of die oorspronklike uitsoeklyne wat deur PEP verskaf is apart hanteer word en of hulle eers gekombineer moet word. Die tweede vraag bepaal of die VEs eers gedupliseer word en dan aan die onderskeie uitsoeklyne toegedeel word en of die VEs eers aan die uitsoeklyne toegedeel word en dan gedupliseer word. Vraag 3 is slegs van toepassing wanneer die VEs eers gedupliseer word en dan toegedeel word aan die uitsoeklyne, en bepaal of die nie-gedupliseerde en gedupliseerde VEs apart of gelyktydig hanteer word. Die laaste vraag spesi seer met behulp van watter metode die VEs toegedeel word aan die onderskeie uitsoeklyne. Drie toedelingsmetodes (sikliese toedeling, vaste lengte subversameling opeenvolgende toedeling, oorblywende hoogste/laagste sikliese toedeling) en 6 bondelalgoritmes word voorgestel. Die gevolgtrekking word gemaak dat die VEs met die hoogste uitsoek frekwensie eerste gedupliseer moet word om die grootste besparing mee te bring in die aantal siklusse om al die VEs uit te soek. Tussen 40{70% van die VEs moet gedupliseer word afhangende van die algoritme wat gebruik word. Die enigste besluit wat 'n noemenswaardige invloed op die aantal siklusse het is die toedelingsmetode. Algoritme 5 en 8 lewer die grootste besparing in die aantal siklusse (40.7% en 39.8% onderskeidelik), beide implementeer die vaste lengte subversameling opeenvolgende toedeling, gevolg deur die bondelalgoritmes.

Les microsatellites, séquences répétées en tandem de période une à six paires de bases, sont des entités génomiques présentes dans tous les organismes qu'ils soient animaux, végétaux ou microbiens. Ils présentent un cycle de vie caractérisé par trois phases principales : une apparition et une maturation, une dynamique à l'état mature, puis une dégénérescence. Nous nous intéressons dans cette thèse à la première phase, l'apparition des microsatellites. <br />Pour traiter ces questions, nous nous sommes basés sur l'analyse de la séquence du génome humain. L'une des lacunes de ce type d'analyse est qu'il faut d'abord extraire les microsatellites du génome, et qu'il existe plusieurs algorithmes de nature et fonctionnement différents. La première partie de cette thèse se concentre donc sur la comparaison de quelques-uns des principaux algorithmes de recherche de répétitions en tandem, et dresse un portait des différentes qualités et limitations de chacun des algorithmes.<br />Deux possibilités majeures sont détaillées, l'apparition par l'intermédiaire d'éléments transposables (ETs), et l'apparition spontanée à partir d'une séquence quelconque. Dans le premier cas, l'étude est focalisée sur le rôle des queues polyA des séquences Alu chez les primates. La question de l'apparition à partir d'une séquence quelconque cherche à établir l'impact de trois mécanismes mutationnels différents sur la création et le développement primordial des microsatellites : la mutation ponctuelle, le glissement de polymérase et la micro-duplication adjacente de quelques nucléotides. Un modèle général d'apparition des microsatellites est aussi proposé, suggérant une dynamique d'apparition plus complexe que ce qui était précédemment supposé.

Neopterygian fishes represent over half of vertebrate richness in the Recent and display staggering phenotypic variety, yet little is known about the first 150 million years of their evolution. Furthermore, neopterygian richness and disparity is highly unevenly partitioned between teleost fishes, with ~29,000 species expressing a plethora of phenotypes, and holostean fishes, with 8 species and just two morphological styles. Fossil phenotypes have the unique ability to illuminate the assembly of neopterygian disparity, and can reveal the pattern by which the uneven partitioning of disparity arose. Morphology and function were quantified with landmarks and six functional traits, respectively, for 356 neopterygian species known globally throughout the first 150 million years of their history. The main axes of morphological and functional variation were derived and used to examine a series of evolutionary questions. Pertinently, they revealed how disparity was accumulated for 60% of the neopterygian radiation; morphological disparity increased through time, whereas functional disparity remained stable. The morphological dataset was expanded to include shape data for 398 species and size data for 471 species. Time scaled supertrees containing 671 mostly Mesozoic, but also living neopterygian species, were created. Together, the trees and traits were used to quantify evolutionary rates and innovation and test the predictions of genome duplication enhanced morphological diversification in teleosts, and the presence of 'living fossil' characteristics in holosteans. The analyses revealed higher rates and greater innovation in teleosts guaranteed to possess duplicated genomes, consistent with the predictions of genome duplication enhanced diversification. The only 'living fossil' characteristic of holosteans is their poor capacity for size innovation, yet they possess relatively high rates of shape evolution. However, estimates of rates and innovation are heavily influenced by timescale choice, emphasising the need for workers to perform their analyses on a variety of plausible timescales to determine the limits of their conclusions.

Notre travail s’est intéressé aux anomalies du développement embryonnaire d’origine génétique en étudiant : -d’une part des patients associant des malformations congénitales multiples plus ou moins associées à un retard mental et à un syndrome dysmorphique, -et d’autre part des patients présentant un phénotype particulier : le spectre oculo-auriculo-vertébral (OAVS) incluant le syndrome de Goldenhar. L’analyse a consisté en l’étude pangénomique de ces patients au moyen de puces à ADN (CGH-array), dans le but d’identifier de nouveaux remaniements chromosomiques avec anomalie du nombre de copies. Nous avons identifié différentes régions variantes et analysé pour chacune leur caractère pathogène potentiel en fonction de leur nature, de leur taille, de leur caractère hérité ou de novo, de leur contenu en gènes et en polymorphismes du nombre de copies, des éléments déjà décrits dans les bases de données et la littérature. Les régions variantes identifiées ont été vérifiées par d’autres techniques de recherche d’anomalies de dosage génique. L’ensemble de ces résultats permet de formuler des hypothèses quant à de nouveaux gènes candidats pour plusieurs symptômes observés, et pour l’OAVS. Ils permettent d’ajouter de nouvelles données à l’ensemble des anomalies décrites depuis quelques années grâce à ces techniques innovantes. / Our work focused on embryonic development abnormalities of genetic origin by studying: - patients with multiple congenital malformations associated or not associated with mental retardation and a dysmorphic syndrome; - patients presenting with the oculo-auriculo-vertebral spectrum (OAVS) that includes the Goldenhar syndrome. Patients were analysed by array-CGH in order to identifying novel chromosomal rearrangements with copy number abnormalities. We have identified several chromosomal regions with copy number variations and analysed for each of those their pathogenic potential, according to their nature, size, either inherited or de novo status, genes and copy number polymorphisms content, and data already reported both in databases and in the literature. The existence of a copy number variation was confirmed by other experimental approaches able to detect gene dosage abnormalities. Our results allowed discussing the possible involvement of candidate genes with respect to the symptoms observed in the patients and to OAVS. They also allowed to add new data to the growing field of copy number variations gathered over the recent years.

Fragmentos de código duplicado, ou clones, são inseridos em aplicativos por serem uma maneira simples de reúso, dentre outros motivos. Clones são, portanto, comuns em programas. No entanto, a atividade de manutenção pode ficar custosa se o código do programa analisado possuir muitos clones, principalmente os semânticos, os quais podem possuir códigos distintos, mas realizam tarefas similares. Nesse sentido, a utilização de ferramentas que automatizam a tarefa de detectar clones é desejável. Ferramentas atuais de detecção de clones semânticos são capazes de identificar esses clones com altas taxas de acerto. No entanto, elas não são capazes de identificar clones semânticos considerando também os fluxos dos procedimentos ou funções que são invocados dentro dos fragmentos de código comparados. Essa limitação pode levar as ferramentas a indicarem clones semânticos falso positivos. Este trabalho apresenta uma técnica de detecção de clones semânticos que considera as chamadas de procedimentos presentes nos programas. Essa técnica apresentou uma taxa de acertos 2,5% maior do que técnicas convencionais de acordo com um benchmark, também desenvolvido neste trabalho. Esse benchmark foi criado com base nas classificações de clones fornecidas por programadores da indústria e da academia. A técnica interprocedimental de detecção de clones semânticos pode ser utilizada para evolução, manutenção, refatoração e entendimento de programas. / Fragments of duplicated code, or clones, are embedded in applications as they are a simple way to reuse code, among other reasons. Clones are therefore common in programs. However, the maintenance activity may be costly if the program code has many clones to analyze, specially semantic clones, which are semantically similar but may have different syntax. In this regard, the use of tools that automate the task of detecting clones is desirable. Current tools for detecting semantic clones are able to identify those clones with high hit rates. However, they are not able to detect semantic clones also considering the flow of procedures or functions that are invoked within the compared code fragments. This limitation can lead the tools to indicate false positive semantic clones. This paper presents a technique that takes into account the procedure calls in programs to detect semantic clones. This technique showed a 2.5% higher hit rate than conventional techniques according to a benchmark also developed in this work. This benchmark was created based on evaluations provided by programmers from academic and industrial settings. The interprocedural semantic clone detection technique can be used for evolution, maintenance, refactoring and understanding of programs.

Fragmentos de código duplicado, ou clones, são inseridos em aplicativos por serem uma maneira simples de reúso, dentre outros motivos. Clones são, portanto, comuns em programas. No entanto, a atividade de manutenção pode ficar custosa se o código do programa analisado possuir muitos clones, principalmente os semânticos, os quais podem possuir códigos distintos, mas realizam tarefas similares. Nesse sentido, a utilização de ferramentas que automatizam a tarefa de detectar clones é desejável. Ferramentas atuais de detecção de clones semânticos são capazes de identificar esses clones com altas taxas de acerto. No entanto, elas não são capazes de identificar clones semânticos considerando também os fluxos dos procedimentos ou funções que são invocados dentro dos fragmentos de código comparados. Essa limitação pode levar as ferramentas a indicarem clones semânticos falso positivos. Este trabalho apresenta uma técnica de detecção de clones semânticos que considera as chamadas de procedimentos presentes nos programas. Essa técnica apresentou uma taxa de acertos 2,5% maior do que técnicas convencionais de acordo com um benchmark, também desenvolvido neste trabalho. Esse benchmark foi criado com base nas classificações de clones fornecidas por programadores da indústria e da academia. A técnica interprocedimental de detecção de clones semânticos pode ser utilizada para evolução, manutenção, refatoração e entendimento de programas. / Fragments of duplicated code, or clones, are embedded in applications as they are a simple way to reuse code, among other reasons. Clones are therefore common in programs. However, the maintenance activity may be costly if the program code has many clones to analyze, specially semantic clones, which are semantically similar but may have different syntax. In this regard, the use of tools that automate the task of detecting clones is desirable. Current tools for detecting semantic clones are able to identify those clones with high hit rates. However, they are not able to detect semantic clones also considering the flow of procedures or functions that are invoked within the compared code fragments. This limitation can lead the tools to indicate false positive semantic clones. This paper presents a technique that takes into account the procedure calls in programs to detect semantic clones. This technique showed a 2.5% higher hit rate than conventional techniques according to a benchmark also developed in this work. This benchmark was created based on evaluations provided by programmers from academic and industrial settings. The interprocedural semantic clone detection technique can be used for evolution, maintenance, refactoring and understanding of programs.