RNA structures and their molecular evolution in HIV: evolution of robustness in RNA structures and theoretical systems

The known functions of RNA structures have expanded of late, such that RNA is considered a more active player in molecular biology. The presence of RNA secondary structure in a sequence should constrain evolution of its constituent nucleotides because of the requirement to maintain the base-pairing regions in the structure. In a previous work, we found support for this hypothesis in nine molecules from various organisms, the exception being a structure found in a protein-coding region of the HIV-1 genome. In this work, I examine the interaction of constraints imposed by RNA structures and host-induced hypermutation on molecular evolution in HIV-1. I conclude that RNA structures in HIV do evolve via compensatory evolution, but that hypermutation can obscure the expected signal. Since RNA's known roles have increased, so have the methods for identification and prediction of RNA structures in genetic sequence. I use a method adapted for searching in multiple coding regions to identify conserved RNA structures throughout the HIV-1 and HIV-2 genomes. I find evidence for several new, small structures in HIV-1, but evidence is less strong for HIV-2. Finally, I consider the evolution of robustness, the property of phenotypic constancy, using RNA structures and two other theoretical model systems. I find that pervasive environmental variation can select for environmental and genetic robustness in all three systems, and conclude that it may be a generic mechanism for the evolution of robustness.