The Genome Sequence of Trypanosoma cruzi , Etiologic Agent of Chagas Disease

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.

Proteomic analysis reveals different composition of extracellular vesicles released by two Trypanosoma cruzi strains associated with their distinct interaction with host cells

“…Most of the MASP hits were found in the EVs from both strains, although different clusters were enriched in each one of them. MASP is a member of a multigenic family, with variable amino acid sequences containing a common N-terminal and a GPI-anchoring sequence [50]. Therefore, these proteins appear to be a principal component of the EVs membranes, differently of the TS family that seems to be more easily released in the soluble form.…”

The direct route: a simplified pathway for protein import into the mitochondrion of trypanosomes

“…The genomes of T. brucei and two other trypanosomatids, Trypanosoma cruzi and Leishmania major, have been completely sequenced and a few highly-conserved components of their mitochondrial protein import machinery annotated [16,20,21]. A recent analysis, using advanced statistical models for sequence comparison has added further to our knowledge of the machinery [2].…”

Protein geranylgeranyltransferase-I of Trypanosoma cruzi

“…Among five GTPase-like proteins found to have the CaaX motif, two of those contain the C-terminal Leu ( Table 2) that are predicted to be T. cruzi PGGT-I substrates. One putative Rab GTPase with CWLM [37] may be a PGGT-II substrate, and other two GTPase-like proteins (TcRho1-CQLF [26] and one with CHFM) seem to serve as selective T. cruzi PFT substrates (Table 3). Four of the T. cruzi PRL protein tyrosine phosphatase homologs and five of the DNAJ homologs were found to have the CaaX ending with Met and Gln (Table 2), respectively, and thus these are predicted to be farnesylated (Table 3).…”