A surprising fact that has emerged in recent years is the great degree of genetic similarity between humans and chimpanzees. Ninety-eight percent of human single-copy DNA (the inherited genetic material) is so similar to chimpanzee DNA that it forms hybrid human-chimpanzee DNA molecules when mixed together under appropriate conditions in a test tube. Dr. Ruvolo will study the 2% of human DNA which does not form hybrid molecules with chimpanzee DNA. Because only a fraction of all DNA consists of genes (protein-coding units), the first question to answer is whether there are any genes in this 2% "human- specific" DNA fraction. If there are, they will be characterized by DNA sequencing. If not, then the genes most different between humans and chimpanzees can still be isolated from the other 98% of human DNA and similarly characterized by DNA sequencing. In either case, Dr. Ruvolo will isolate those genes maximally different between humans and chimpanzees. These DNA sequences will be compared with all known DNA sequences by computer search techniques to test whether, and in what way, they resemble any known genes. This research is important because it develops a general method for identifying genes maximally different between closely- related species. Such genes are useful in population biology and in systematics for determining how groups and species are related to one another. Extension of this method may allow isolation of genes common to groups of organisms, such as "primate-specific" or "mammal-specific" genes. Isolation of the most rapidly- evolving genes in humans can help partition the human genome into ancient and modern segments.