Comprehensive genomic analysis of Trypanosoma rangeli reveals key insights into the biology and evolution of this non-virulent American mammalian trypanosome

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Abstract

ABSTRACT Background Trypanosoma rangeli is a non-virulent hemoflagellate protozoan parasite that infects mammals, including humans, in Central and South America. It is primarily transmitted through the bites of triatomine bugs and shares an overlapping geographical distribution with T. cruzi , as well as triatomine vectors and mammalian hosts, and various shared surface antigens. The life cycle of T. rangeli differs from those of other human-infecting trypanosomes, such as T. cruzi and T. brucei , and the molecular mechanisms underlying host-parasite and host-vector interactions are not well understood, demanding improved molecular and genomic resources. Results The use of a hybrid approach to sequence and assemble the T. rangeli genome, complemented by transcriptomics and proteomics for functional gene annotation, led to the generation of the near-complete genome sequence of the parasite. Detailed intra- and inter-specific comparative genomics allowed analysis of polymorphisms, genome structure and improved resolution of genes coding for important surface molecules such as Mucins, TASV and GP63. Conclusions The improved T. rangeli genome assembly, combined with comparative genomics has yielded novel biological insights. These included the first description of a metalloprotease activity, attributed to specific GP63 genes that are absent in Leishmania species. In addition, a TASV gene family that is absent in T. cruzi was identified, which indicates a possible role in the T. rangeli infection process.
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Abstract

Background Trypanosoma rangeli is a non-virulent hemoflagellate protozoan parasite that infects mammals, including humans, in Central and South America. It is primarily transmitted through the bites of triatomine bugs and shares an overlapping geographical distribution with T. cruzi, as well as triatomine vectors and mammalian hosts, and various shared surface antigens. The life cycle of T. rangeli differs from those of other human-infecting trypanosomes, such as T. cruzi and T. brucei, and the molecular mechanisms underlying host-parasite and host-vector interactions are not well understood, demanding improved molecular and genomic resources.

Results

The use of a hybrid approach to sequence and assemble the T. rangeli genome, complemented by transcriptomics and proteomics for functional gene annotation, led to the generation of the near-complete genome sequence of the parasite. Detailed intra- and inter-specific comparative genomics allowed analysis of polymorphisms, genome structure and improved resolution of genes coding for important surface molecules such as Mucins, TASV and GP63.

Conclusions

The improved T. rangeli genome assembly, combined with comparative genomics has yielded novel biological insights. These included the first description of a metalloprotease activity, attributed to specific GP63 genes that are absent in Leishmania species. In addition, a TASV gene family that is absent in T. cruzi was identified, which indicates a possible role in the T. rangeli infection process. Competing Interest Statement The authors have declared no competing interest. Footnotes Corrections on two of the authors names (minor typos) - ABBREVIATIONS - AB - Allele Balance - Bp - Base pairs - CCNV - Chromosome Copy Number Variation - CDS - Coding sequence - DGF-1 - Disperse Gene Family 1 - GO - Gene Onthology - GP - Glycoprotein - GPI - Glycosylphosphatidylinositol - Kb - Kilobases - Kbp - Thousand base pairs - kcal/mol - Kilocalories per mole - kDa - Kilodaltons - KMP - Kinetoplastid Membrane Protein - mAb - Monoclonal antibody - MASP - Mucin-Associated Surface Proteins - Mb - Megabase - Mbp - Million base-pairs - pTM - Predicted template modelling - RDC - Read Depth Coverage - RHS - Retrotransposon Hot Spot - RMSD - Root Mean Square Deviation - RNAi - RNA interference machinery - SNP - Single Nucleotide Polymorphism - TASV - Trypomastigote, Alanine, Serine and Valine rich protein glycoprotein family - VSG - Variable Surface Glycoprotein.

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