The ste3 pheromone receptor gene of Pneumocystis carinii is surrounded by a cluster of signal transduction genes

Although the clinical aspects of Pneumocystis carinii pneumonia are well ch aracterized, the basic biology of the causative organism is poorly understo od. Most proposed life cycles of P. carinii include both asexual and sexual replicative cycles. The two most prominent morphological forms are a troph ic form, thought to undergo asexual replication by binary fission, and a cy stic form or ascus containing intracystic bodies or ascospores, the product s of sexual replication. To facilitate the Pneumocystis genome project, a P . carinii f. sp. carinii genomic cosmid library and an additional lambda cD NA library were generated. A partial expressed sequence tag database, creat ed as part of the genome project, revealed the transcription of meiosis-spe cific genes and other genes related to sexual reproduction. The ortholog of Ste3, an a-factor pheromone receptor, was cloned and genes surrounding the ste3 locus were examined. Clustered around the ste3 gene are genes encodin g elements functional in the pheromone response signal transduction cascade of model fungal organisms. These include the SteB20 protein kinase, the St e12 homoeodomain transcriptional regulator, a potential pheromone mating fa ctor, and other DNA-binding proteins. The genomic organization of the ste3 locus bears significant similarity to that of the mating locus recently des cribed in Crytococcus neoformans. The P. carinii genome contains much of th e genetic machinery necessary for pheromone responsiveness, and these data support the existence of a sexual replication cycle.