This project is aimed at characterizing influences on synonymous codon usage in prokaryotes, eukaryotes, and viruses. Careful assessment of codon usage is of value to those whose interests include the biochemistry of gene expression, horizontal gene transfer (both in evolution and in recombinant DNA technology), gene prediction, selection conflicts, and molecular population genetics and systematics. The project has four specific aims: (1) to rigorously assess codon preferences in phylogenetically diverse organisms; (2) to study conflicts that interfere with selection on codon usage; (3) to study the coevolution of human and viral genomes with respect to codon usage; and (4) to study ongoing selection on codon usage in viruses, bacteria and Drosophila. Software for reading and analyzing genome sequences will be updated as necessary. Codon preferences will be identified by correlations with gene expression and/or multivariate statistical methods. Contributors to within-species variance in preferred codon usage (e.g., among- and within-gene variance in selection intensity, regional variation in compositional biases, regional variation in recombination rate, among-gene variation in gene spacing) will be inferred by statistical analysis. Based on the results of prior Drosophila and yeast studies, analyses will be performed to distinguish between selection conflicts associated with linkage and those associated with antagonistic pleiotropy in closely spaced genes. Based on data that indicate coevolution of phage and bacterial hosts, codon usage of viruses that infect humans should depend on the human gene expression machinery. Phylogenies will be constructed for closely related viruses that infect humans, along with their relatives that infect other mammals, and codon substitutions will be inferred and analyzed using population genetic approaches to test for selection on codon usage. Analysis of virus codon usage will provide information on both its adaptive significance and on the codon preferences that may be shared by highly expressed human genes. Similar analyses will be performed on closely related bacteria and Drosophila. At least twenty genes will be sequenced in several strains of Drosophila, and patterns of polymorphism and divergence will be used to test for the ongoing action of natural selection on codon usage. We will focus, in particular, on variation in the relative intensity of selection (1) in different regions of genes and (2) on different amino acids. ? ?
