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Title: Using phylogenetic models to characterise natural selection from molecular data
Author: Tamuri, A. U.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2012
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Molecular phylogenetics is the application of mathematical and computational techniques to analyse molecular sequences and make inferences about their evolutionary relationships. There is substantial interest in developing probabilistic models of evolution that effectively detect, locate and characterise different type of selection in genes, driven by the relationship of selection to protein structural constraints and function. In this thesis we propose novel approaches that can be used not only to detect the presence of selection but also to characterise its kind and strength. We first develop a phylogenetic method to identify changes in selective constraints and use it to identify those mutations that allow influenza viruses from avian origin to spread successfully in the human population. The model explicitly takes into account differences in the equilibrium frequencies of amino acids in different hosts and locations. We then use these results to develop a measure of the level of adaptation of any given influenza virus sequence to the selective constraints imposed by avian or human hosts. We show that adaptation to the human host has been gradual when applied to historical data. Our results also indicate that the 1918 influenza virus had undergone a period of pre-adaptation prior to 1918 when compared to the adaptation of other avian influenza viruses. Finally, we develop a codon-based model of mutation-selection to estimate the distribution of selection coefficients and find that we can recover distributions similar to those expected by population genetics theory. We show that the distribution of mammalian mitochondrial proteins is bimodal with the majority of mutations being deleterious. When we apply the model to the PB2 influenza polymerase protein following a host shift from birds to humans, we find a trimodal distribution with a significant proportion of advantageous substitutions.
Supervisor: Goldstein, R. A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available