| Summary: | Understanding genetic variation underlying phenotypic differences between populations and species is an active area of research in evolutionary and medical genetics. In this thesis, I present a thorough analysis of pooled sequencing data from three experimental evolution experiments conducted in Drosophila melanogaster. In Chapter 1, I give a general overview of the experimental evolution approach in investigating genetic basis of complex traits in model organisms. In Chapter 2, using the E&R approach and a generalized linear mixed model I show several thousand standing variants show marked allele frequency divergence in response to hypoxia. I demonstrate that many of these variants cluster together in certain genomic regions, indicating that hitchhiking effects are prevalent in experimental evolution. By filtering the variants using stringent filters, I identify about one hundred hypoxia associated genes in flies. Using RNAi mediated knockdown of gene expression, I show that candidate genes affect survival in hypoxia. Finally, I show parallel adaptation in response to hypoxia in experimentally evolved flies and four geographically distinct high-altitude human populations. In Chapter 3, using the methods developed in Chapter 2, I show that genetic variants responding to egg size selection are also primarily standing variations involving over one hundred genes. The results from these two chapters provide empirical evidence that standing variation can be primary contributors in evolution of complex traits. However, a vast majority of standing variants usually appear neutral, indicating that there may be mechanisms that buffer their effects. In Chapter 4, I show one such mechanism that involves microRNAs. I demonstrate that microRNA-9a (miR-9a) plays a critical role in dampening the effect of genomic diversity in Drosophila proneural network. Finally, in the final chapter, I summarize the findings from these three experimental evolution studies and highlight several steps to improve this approach in future.
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