ABSTRACT
Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
Subject(s)
Genome, Protozoan , Protozoan Proteins/genetics , Sequence Analysis, DNA , Trypanosoma cruzi/genetics , Animals , Chagas Disease/drug therapy , Chagas Disease/parasitology , DNA Repair , DNA Replication , DNA, Mitochondrial/genetics , DNA, Protozoan/genetics , Genes, Protozoan , Humans , Meiosis , Membrane Proteins/chemistry , Membrane Proteins/genetics , Membrane Proteins/physiology , Multigene Family , Protozoan Proteins/chemistry , Protozoan Proteins/physiology , Recombination, Genetic , Repetitive Sequences, Nucleic Acid , Retroelements , Signal Transduction , Telomere/genetics , Trypanocidal Agents/pharmacology , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi/chemistry , Trypanosoma cruzi/physiologyABSTRACT
Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.
