The primary objective of this research is to assess alterations in the genome-wide expression pattern caused by accumulation of spontaneous deleterious mutations in the nematode Caenorhabditis elegans. Mildly deleterious mutations play a central role in a broad array of evolutionary and genetic phenomena, including the distribution of the transposable elements, the level of nucleotide diversity in various regions of the genome, the magnitude of inbreeding depression, the evolution of sex and recombination, the degeneration of Y chromosome, the senescence and extinction of endangered species. Presently the knowledge of deleterious mutations has been limited to two levels of biological organization: the DNA and the organism. Difficulty in predicting the effects of most DNA mutations on organismal phenotypes limits the first. The second is unsatisfactory, because the high phenotypic variances of the fitness-related traits obscure effects of mildly deleterious mutations. This project will survey the consequences of spontaneous deleterious mutations on the genome-wide gene expression level because microevolutionary changes in fitness are likely caused by mutations that change gene expression, rather than mutations that alter protein structure. The mutant strains used for this study will be mutation-accumulation lines, which have been created by propagating worms from single individuals from a population without selection for 400 generations. The combination of the complete genome sequence of C. elegans allowing DNA microarrays available to screen genome-wide expression, and the longest mutation-accumulation lines among eukaryotes presents an unparalleled opportunity to investigate deterioration of the global gene expression by spontaneous deleterious mutations. This work will contribute to establishing a basis for prediction of the evolutionary and genetic consequences of spontaneous mutations on genome-wide expression patterns.
