Genetic divergence of the dihydrofolate reductase and dihydropteroate synthase genes in Pneumocystis carinii from 7 different host species

To investigate the phylogenetic and therapeutic implications of the genetic divergence in the dihydrofolate reductase (DHFR) and dihydropteroate synth ase (DHPS) genes among different Pneumocystis carinii strains, these 2 gene s in P. carinii obtained from 7 different host species were sequenced. Pair wise comparison of the DHPS sequences demonstrated 6%-24% and 6%-30% diverg ence in the nucleotide and deduced amino acid sequences, respectively. The DHFR gene was even more divergent, with differences of 15%-34% and 18%-42% in the nucleotide and deduced amino acid sequences, respectively. Phylogene tic analysis of DHFR and DHPS sequences revealed that all P. carinii strain s were confined within a distinct group that was closely related to ascomyc ete fungi and that human-derived P. carinii was most closely related to mon key-derived P. carinii. Recognizing the substantial differences in the DHFR and DHPS genes among P. carinii from different host species has important implications for drug discovery and the development of new diagnostic metho ds.