Natural selection in molecular evolution: Genome-scale, parsimony-based approach

The analysis and comparison of genome sequences allows us to address the fundamental questions of the evolutionary theory, assigning quantitative parameters to processes that could previously only be guesstimated. Elucidating the relative roles of natural selection and neutral processes in evolution is arguably the main of these questions, and was the ultimate objective of this work.; In Chapters 2 and 3, an approach to inference of positive selection is suggested which is based on temporal non-uniformity of substitution rates. Analysis of rapidly evolving amino acid sites in mammalian coding sequences (Chapter 2) revealed the role of positive selection on changing selective landscapes. In complex phylogenies of four genes of HIV-1 (Chapter 3), positive selection is shown to be important in conservative amino acid positions.; Inferring the role of selection can be restated as inferring the distribution of selection coefficients associated with the accepted mutations. This distribution can be informed by the rate of parallel evolution. In Chapter 4, I use the comparisons of coding sequences from several groups of species to estimate the mean selective coefficient associated with the accepted mutations, and the maximal fraction of neutral sites among the sites capable of evolving.; The neutral theory of molecular evolution predicts that the identity of amino acids at some sites does not affect the fitness of the encoded protein, and can be biased by other forces. Under strong continual positive selection, it can be influenced by the structure of the genetic code. As Chapter 5 shows, the patterns of evolution of some viral proteins are consistent with this prediction, possibly indicating the role of the structure of the genetic code in determining the amino acid sequence composition.; A large fraction of genome sequences which is not coding for proteins is also subject to natural selection due to its functional significance. The analysis of the distribution of selective constraint in yeast cis -regulatory regions (Chapter 6) revealed a complex pattern of conservation and functional importance. The functional TATA box sequences evolve between closely related species at substantial rate (Chapter 7), although the selective importance of this evolution remains to be determined.