Chlamydia trachomatis is the cause of a variety of sexually transmitted diseases and is the most prevalent reported disease in the United States. Chlamydia are very distantly related to other eubacteria and they are classified in their own order and family, which contain one genus. Of the three major species of Chlamydia, C. trachomatis and C. pneumoniae are major human pathogens. DNA homology between different C. trachomatis strains is greater that 96 percent with nearly identical Bam H1 restriction fragment length patterns. Thus determination of the complete nucleotide sequence of one C. trachomatis strain will be sufficient to fundamentally characterize the biovars causing human disease. While other Chlamydia species significantly differ at the nucleotide level, they share surprising and significant amino acid homology for each of the proteins thus far characterized. Consequently, genomic sequence data for C. trachomatis can be expected to define much of the biological capacity for the genus. Chlamydiae have one of the smallest procaryote chromosomes consisting of 1,045 million bases. In the face of hundreds of millions of individuals infected with chlamydiae, surprisingly little is known about the biology, physiology, immunology, pathogenesis and genetics of those organisms. This paucity of understanding is not for lack of interest but simply emphasizes how difficult these organisms are to study. Genetic approaches to study chlamydiae have been very limited. The difficulties in making chlamydial mutants, the lack of expression of chlamydial genes in other hosts, and especially the lack of a system to transform chlamydiae with exogenous DNA are major handicaps. The investigators propose that knowledge of the chlamydial genome sequence will immediately catapult the understanding of the major biosynthetic capabilities of this organism by identification of homologous genes to other free-living organisms and provide an enduring and important data base from which to research other common and unique genes relevant to the fundamental biology of chlamydiae.
The specific aims are: 1) Determine the DNA sequence of the C. trachomatis chromosome, and 2) Establish a DNA sequence data base for the C. trachomatis genome.
