This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this project is to understand the contribution of gene duplication and deletion to genetic variation and adaptation. Gene duplications and deletions contribute significantly to genetic syndromes in humans and recent evidence suggests that humans are surprisingly diverse with respect to gene copy numbers. Moreover, gene duplications have been the primary source of novel functions in evolution and they have been particularly important in the evolution of the immune system. This project uses the nematode, Caenorhabditis elegans, an established model system in genetics and developmental biology, to 1) measure the rate of gene duplication and deletion genome wide, 2) analyze polymorphism caused by duplication and deletion in natural populations and 3) test the role of gene duplication and deletion in genetic adaptation. Comparative Genome Hybridization on DNA microarrays is used to test the hypothesis that gene duplications are more frequent than the per base pair nucleotide substitution rate, and that gene copy number differences are an important component in genetic variation and play a role in adaptation through selection on gene dosage. The gene duplication/deletion rate will be tested on DNA from lines of C. elegans that have been subjected to single individual bottlenecks for 465 generations so that natural selection against deleterious mutations has been almost eradicated. Gene-copy number polymorphism will be analyzed in natural isolates of C. elegans and the role of gene duplications/deletions in adaptation will be tested in populations of C. elegans that are adapting to laboratory conditions following severe decline in fitness.
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