Graur, Dan2017-06-232017-06-23May 20142014-05May 2014Portions of this document appear in: Nicholas Price, Reed A. Cartwright, Niv Sabath, Dan Graur, Ricardo B.R. Azevedo; Neutral Evolution of Robustness in Drosophila microRNA Precursors. Mol Biol Evol 2011; 28 (7): 2115-2123. doi: 10.1093/molbev/msr029http://hdl.handle.net/10657/1823During my dissertation I used a combination of comparative and phylogenetic approaches to test for selection on genic regions. Specifically, I tested for mutational and environmental robustness in Drosophila pre-miRNAs, as well as selection on synonymomous and nonsynonymous sites in mammalian protein coding genes. Contrary to previous claims of selection for mutational robustness in mammalian pre-miRNAs, I demonstrate that mutational robustness evolved neutrally in Drosophila pre-miRNas. Furthermore, I show that mutational robustness did not evolve as a byproduct of selection for environmental robustness. In Chapter 3, I identify orthologous processed pseudogenes and use them to test for selection on synonymous sites. By estimating the rate of substitution at synonymous sites in genes (d_S), and corresponding sites in pseudogenes (d_ψ), I demonstrate that only about ~8% of synonymous changes could possibly be under selection. This is in stark contrast to the ~30% previously claimed. However, I show that both deviations from neutrality can be caused by an increase in divergence between the sequences examined, in combination, with a difference in nucleotide composition between genes and pseudogenes. In the last part of my dissertation, I estimate selection on nonsynonymous sites in mammals (d_N/d_S), and examine the previously claimed positive correlation between generation time and selection. To ensure the correct estimation of selection, I examine the effects of sequencing errors and alignment quality. After accounting for phylogenetic independence, I find no correlation between generation time and selection. Furthermore, I find a significant decrease in the efficiency of selection in monkeys, after the simian and prosimian split.  application/pdfengThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).SelectionGenic regions2017-06-23Thesisborn digital