With the aim of understanding the process and mechanism of molecular evolution, three mutually related research projects are proposed. The first project is for identifying positive Darwinian selection at the DNA level by examining the relative rates of synonymous and nonsynonymous (amino acid altering) nucleotide substitution. Both statistical analyses of DNA sequence data and mathematical modeling of nucleotide substitution will be conducted. Special attention will be given to the active and contact sites of proteins involved in the immune and nonimmune systems in vertebrates. We are particularly interested in examining whether overdominant selection is involved in the antigen-recognition sites of proteins concerned with the immune system. The second project is intended to clarify the effect of population bottlenecks on the divergence of nucleotide sequences within and between populations. Stochastic theory of population genetics will be used to solve this problem, and the mathematical theory developed will be applied to analyze data on mitochondrial DNA phylogenies. The third project is to study the evolution of the major histocompatibility complex gene family, which is one of the most complicated genetic systems in vertebrates. Analyzing DNA sequences available, we will examine the evolutionary relationships of genes within and between loci as well as within and between species. The functional change of different groups of genes in the evolutionary process will also be investigated.
