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Inferring Evolutionary Processes of HumansLi, Sen January 2012 (has links)
More and more human genomic data has become available in recent years by the improvement of DNA sequencing technologies. These data provide abundant genetic variation information which is an important resource to help us to understand the evolutionary history of humans. In this thesis I evaluated the performance of the Approximate Bayesian Computation (ABC) approach for inferring demographic parameters for large-scale population genomic data. According to simulation results, I can conclude that the ABC approach will continue to be a useful tool for analysing realistic genome-wide population-genetic data in the post-genomic era. Secondly, I implemented the ABC approach to estimate the pre-historic events connected with the “Bantu-expansion”, the spread of peoples from West Africa. The analysis based on genetic data with a large number of loci support a rapid population growth in west Africans, which lead to their concomitant spread to southern and eastern Africa. Contrary to hypotheses based on language studies, I found that Bantu-speakers in south Africa likely migrated directly from west Africa, and not from east Africa. Thirdly, I evaluated Thomson's estimator of the time to most recent common ancestor (TMRCA). It is robust to different recombination rates and the least-biased compared to other commonly used approaches. I used the Thomson estimator to infer the genome-wide distribution of TMRCA for complete human genome sequence data in various populations from across the world and compare the result to simulated data. Finally, I investigated and analysed the effects of selection and demography on genetic polymorphism patterns. In particular, we could detect a clear signal in the distribution of TMRCA caused by selection for a constant-size population. However, if the population was growing, the signal of selection will be difficult to detect under some circumstances. I also discussed and gave a few suggestions that might lead to a more realistic path of successful identification of genes targeted by selection in large-scale genomic data.
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Sur l'origine de Toxoplasma Gondii : approches phylogénétique et spatialement-explicite pour la détermination de l'origine géographique d'un parasite ubiquiste / On the origin of Toxoplasma gondii : phylogenetic and spatially explicit approaches for the identification of the geographical origin of an ubiquitous parasiteBertranpetit, Emilie 19 December 2016 (has links)
Toxoplasma gondii, protozoaire ubiquitaire chez les mammifères et les oiseaux, est l’agent étiologique de la toxoplasmose, une maladie posant un réel problème de santé publique dans le monde avec environ 200 000 nouveaux cas de toxoplasmose congénitale chaque année. Il a été montré que la sévérité clinique de la toxoplasmose variait en fonction des régions géographiques, avec en particulier l’Amérique du Sud qui paie le plus lourd tribu de cette maladie. Malheureusement, les mécanismes de ces disparités géographiques sont encore peu compris et l’origine géographique ainsi que l'histoire évolutive du pathogène sont encore incertaines. Une collection mondiale de 168 isolats de T. gondii recueillis dans 13 populations de 5 continents a été séquencée pour cinq fragments de gènes (140 single nucleotide polymorphisms à partir de 3153 bp par isolat). La phylogénie basée sur les méthodes de Maximum de vraisemblance avec une estimation de l’âge du plus récent ancêtre commun (TMRCA) et des analyses géostatistiques ont été réalisées afin d’inférer l’origine hypothétique de T. gondii. Nous montrons que les souches actuelles de ce parasite ont vraisemblablement évolué à partir d’un ancêtre Sud-Américain il y a environ 1,5 million d’années et avons reconstruit la propagation mondiale du pathogène qui a suivi. Cette émergence est beaucoup plus récente que l’apparition de la forme ancestrale de T. gondii il y a environ 11 Ma et est postérieure à l’arrivée des félidés dans cette partie du monde. Nous proposons que la lignée ancestrale de T. gondii ait été introduite en Amérique du Sud avec les félidés et que l’évolution de l’infectivité orale des kystes tissulaires à travers le carnivorisme ainsi que la diversification des félidés dans cette région du monde a permis l'apparition d'une nouvelle souche ayant une capacité de transmission beaucoup plus efficace que la lignée ancestrale, ce qui lui a permis de la supplanter et d’avoir une distribution pandémique. / Toxoplasma gondii, a protozoan found ubiquitously in mammals and birds, is the etiologic agent of toxoplasmosis, a disease causing substantial Public Health burden worldwide, including about 200,000 new cases of congenital toxoplasmosis each year. Clinical severity has been shown to vary across geographical regions with South America exhibiting the highest burden. Unfortunately, the drivers of these heterogeneities are still poorly understood, and the geographical origin and historical spread of the pathogen worldwide are currently uncertain. A worldwide sample of 168 T. gondii isolates gathered in 13 populations was sequenced for five fragments of genes (140 single nucleotide polymorphisms from 3,153 bp per isolate). Phylogeny based on Maximum likelihood methods with estimation of the time to the most recent common ancestor (TMRCA) and geostatistical analyses were performed for inferring the putative origin of T. gondii. We show that extant strains of the pathogen likely evolved from a South American ancestor, around 1.5 million years ago, and reconstruct the subsequent spread of the pathogen worldwide. This emergence is much more recent than the appearance of ancestral T. gondii, believed to have taken place about 11 My ago, and follows the arrival of felids in this part of the world. We posit that an ancestral lineage of T. gondii likely arrived in South America with felids and that the evolution of oral infectivity through carnivorism and the radiation of felids in this region enabled a new strain to outcompete the ancestral lineage and undergo a pandemic radiation.
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