The genome of the kinetoplastid parasite, Leishmania major

Abstract

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.

Fig. 1

Trypanosomatid RNA polymerase subunits and transcription factors. (A) The TRIBE-MCL (table S2) protein families containing subunits of human RNA polymerase II (Rpb-1 to -12) and basal transcription factors (TBP and TFII-B, -E, -F, -H) are shown as ovals and circles respectively. Families containing Tritryp sequences are colored sepia and indicated by “+” or “(+)” (when the Tritryp gene is not a direct ortholog), whereas families lacking Tritryp sequences are indicated by “−” or “(−)” (when a Tritryp ortholog was detected only by BlastP analysis). Orthologs present in other taxa are indicated by “+”. The genomes queried for each taxon are detailed in (10). (B) Subunits of the yeast TFIIS, Elongator, Cdc73/Paf1, and Elongin complexes are displayed in blue boxes, with the first column of the row indicating whether Tritryp sequences with high “X”, weak “(X)”, or no “∼” similarity were detected. The remaining columns of the row are marked as in (A); “?” indicates that the S. cerevisiae sequence is not present in the TAP reference set.

Fig. 2

Protein domains associated with regulation of gene expression in trypanosomatids. The Pfam accession numbers for HMMs that match Tritryp predicted proteins are shown at the left, with the next column indicating the total number of sequences matched in the Tritryp genomes. The matches in individual genomes (normalized by genome size) are shown by the bar graphs, expressed per 10,000 genes. Abbreviations: L. major (L_m); T. brucei (T_b); T. cruzi (T_c); P. falciparum (P_f); Cryptosporidium parvum (C_p); S. pombe (S_p); S. cerevisiae (S_c); Magnaporthe grisea (M_g); N. crassa (N_c); A. thaliana (A_t); C. elegans (C_e); D. melanogaster (D_m); Mus musculus (M_m); Rattus norvegicus (R_n); H. sapiens (H_s). The two numbers immediately to the right of the bar graphs show the maximum and minimum matches observed for all genomes, and the next column shows the mean ± SD for the 10 free-living eukaryotes. The Pfam description of the HMM is shown at the right, with the normalized and actual (in square brackets) number of matches in the L. major, T. brucei, and T. cruzi genomes shown beneath.