In both vertebrates and invertebrates, endogenous clocks governing the expression of biological periodicity are localized in the central nervous system. One such clock in the fruitfly Drosophila has been the subject of extensive genetic and molecular studies. These studies have resulted in the identification of several genes whose products determine the properties of biological clocks in Drosophila. One of these genes, per, has been cloned and sequenced, making it possible to elucidate the structure of a clock protein. The presence of per-homologous transcripts in deletion-bearing mutants lacking the per locus suggests that a family of related clock genes exists in Drosophila. Dr. Jackson has begun to test this hypothesis by using reduced-stringency hybridization conditions to isolate per-homologous clones from phage/Drosophila cDNA and genomic libraries. In order to further characterize these putative biological rhythm genes, he proposes the following studies. (1) He will characterize the tissue and developmental expression of per-homologous genes. (2) The chromosomal location of these genes will be determined, and (3) genetic methods will be used to assess their role in the development and maintenance of biological rhythms. (4) The complete DNA sequence of one of these related genes will be derived in order to predict the primary structure of a per-homologous protein. Completion of these aims will provide information on the genetic basis of biological rhythms.
