University of Sussex
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Patterns of natural selection across the human genome

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posted on 2023-06-10, 02:02 authored by Vivak Soni
Natural selection is one of the key mechanisms by which evolution proceeds. It is the process by which different allelic types become more or less common in successive generations of a population due to differential genotypic responses to the environment. In this thesis I investigate genome wide patterns of natural selection in hominids. I investigated the prevalence of balancing selection in the human genome using a novel method based on the McDonald-Kreitman (MK) test framework. Having shown that this test is robust to demographic change and that it can also give a direct estimate of the number of shared polymorphisms that are directly maintained by balancing selection, I applied this method to population genomic data from humans, finding that more than a thousand nonsynonymous polymorphisms are subject to balancing selection. It has been shown that the rate of adaptive evolution can be affected by numerous factors at the gene level and the site level. I correlated the rates of adaptive (wa) and non-adaptive (wna) evolution with four gene-level factors: recombination rate, gene age, gene length, and gene expression. For each factor I controlled for the other three factors in turn, finding a significant positive correlation between recombination rate and rates of adaptive and non-adaptive evolution. I also investigated the correlation between the rates of adaptive and non-adaptive evolution and four site-level factors: relative solvent accessibility, amino acid volume difference, amino acid polarity difference and a measure of evolutionary dissimilarity, pN/pS, finding similar correlations to those found previously in Drosophilids, except in the case of pN/pS, where the slope of the relationship is significantly lower in hominids. This can be explained by contracting population size along the human and chimpanzee lineages. The statistic pN/pS is strongly correlated to the mean strength of selection acting against deleterious mutations, and this is expected to attenuate the relationship between the rate of adaptive evolution and pN/pS as we observe. Effective population size (Ne) is an important quantity in determining the effectiveness of selection. It can vary not only between species but also across genomes. I investigate patterns of diversity across the human genome. Neutral diversity is expected to be a function of the mutation rate, effective population size and mean genealogy length. Surprisingly I find that the variation in diversity is less than the variation in the mutation rate, inferred from de novo mutation data. This suggests that the effective population size of a genomic region is negatively related to the mutation rate. I fit models and find that the effects of linked selection must be strong to explain the observed data.


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University of Sussex

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