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.
Infection with pathogenic Leishmania results in a spectrum of human diseases, termed the leishmaniases, with an annual incidence of 2 million cases in 88 countries (1). Leishmania parasites are transmitted by sand flies as proliferative promastigotes, which differentiate into nondividing metacyclic forms before inoculation into the vertebrate host and phagocytosis by macrophages. The metacyclics subsequently differentiate into amastigotes, which proliferate in the phagolysosome, leading to macrophage lysis and serial infection of other macrophages (2). The outcome of infection is determined by the infecting species, host genetic factors, and the immune response.
Old World Leishmania (L. donovani and L. major groups) have 36 chromosome pairs (0.28 to 2.8 Mb) (3), whereas New World species have 34 or 35, with chromosomes 8+29 and 20+36 fused in the L. mexicana group and 20+34 in the L. braziliensis group (4). Gene order and sequence are highly conserved among the ~30 Leishmania species (5). The genome sequence of L. major MHOM/IL/81/Friedlin was determined on a chromosome-by-chromosome basis. Here we present the structure and content of the L. major genome, with an emphasis on fundamental molecular processes such as chromatin remodeling, transcription, RNA processing, translation, posttranslational modification, and protein turnover. We also discuss the synthesis of complex surface glycoconjugates that are characteristic of Leishmania species and essential at the host-parasite interface. Discussion of cytoskeleton, metabolism, and transport can be found in the accompanying description of the Trypanosoma brucei genome (6), while signaling pathways, DNA repair, recombination, and replication are discussed in the Trypanosoma cruzi article (7).