9806913 Eichler Gene duplication is one of the primary forces of evolutionary change. It is by this process that new genes are believed to arise in the genome of an organism. Despite its importance in evolution, the mechanism by which this process occurs is not well understood. The objective of this proposal is to investigate one such mechanism that has been recently identified within the genomes of higher primates. An unusual bias for duplicating segments containing entire genes or gene-segments has been documented for regions near the centromeres of primate chromosomes. Dr. Eichler will conduct experiments to determine precisely what segments of the genome have been duplicated, when the duplication events occurred within an evolutionary timeframe, how large are the duplicated segments, where these duplication events have occurred and what molecular sequences define the breakpoints between ancestral and duplicated loci. Due to the unusually high degree of sequence similarity between these segments, the study will focus primarily on man and his most closely related species (chimpanzee, gorilla and orangutan). The chromosomes of multiple individuals from each species will be analyzed to determine if these events contribute to differences in the architecture of the genome both between species and within species. The results of this process should provide important clues in understanding the mechanism which has been responsible for the distribution of these segments across the primate genome and help to explain the bias for these events to occur near the centromeres of chromosomes. Furthermore, the results of these studies should shed light on the role of gene duplication in the evolution and organization of chromosomes in man and other primates.