Trypanosoma rangeli is phylogenetically closer to Old World trypanosomes than to Trypanosoma cruzi.

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Trypanosoma rangeli and Trypanosoma cruzi are generalist trypanosomes sharing a wide range of mammalian hosts; they are transmitted by triatomine bugs, and are the only trypanosomes infecting humans in the Neotropics. Their origins, phylogenetic relationships, and emergence as human parasites have long been subjects of interest. In the present study, taxon-rich analyses (20 trypanosome species from bats and terrestrial mammals) using ssrRNA, glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH), heat shock protein-70 (HSP70) and Spliced Leader RNA sequences, and multilocus phylogenetic analyses using 11 single copy genes from 15 selected trypanosomes, provide increased resolution of relationships between species and clades, strongly supporting two main sister lineages: lineage Schizotrypanum, comprising T. cruzi and bat-restricted trypanosomes, and Tra[Tve-Tco] formed by T. rangeli, Trypanosoma vespertilionis and Trypanosoma conorhini clades. Tve comprises European T. vespertilionis and African T. vespertilionis-like of bats and bat cimicids characterised in the present study and Trypanosoma sp. Hoch reported in monkeys and herein detected in bats. Tco included the triatomine-transmitted tropicopolitan T. conorhini from rats and the African NanDoum1 trypanosome of civet (carnivore). Consistent with their very close relationships, Tra[Tve-Tco] species shared highly similar Spliced Leader RNA structures that were highly divergent from those of Schizotrypanum. In a plausible evolutionary scenario, a bat trypanosome transmitted by cimicids gave origin to the deeply rooted Tra[Tve-Tco] and Schizotrypanum lineages, and bat trypanosomes of diverse genetic backgrounds jumped to new hosts. A long and independent evolutionary history of T. rangeli more related to Old World trypanosomes from bats, rats, monkeys and civets than to Schizotrypanum spp., and the adaptation of these distantly related trypanosomes to different niches of shared mammals and vectors, is consistent with the marked differences in transmission routes, life-cycles and host-parasite interactions, resulting in T. cruzi (but not T. rangeli) being pathogenic to humans.This study was supported by grants awarded to MMGT and EPC from CNPq (National Council for Scientific and Technological Development) PROAFRICA, PROSUL and UNIVERSAL programs, CAPES (Coordination for the Improvement of Higher Education Personnel) PNIPB, PNPD and PROTAX programs, and FAPESP (São Paulo Research Foundation; process 2016/07487-0). Genome sequencing was supported by the Assembling the Tree of Life (ATOL) Project of the National Science Foundation, USA (NSF DEB-0830056), and TCC-USP (Trypanosomatid Culture Collection of the University of São Paulo) projects. OEA received PhD fellowships from CNPq (PROTAX) and COLCIENCIAS (Administrative Department of Science, Technology and Innovation, Colombia); PAO is a postdoctoral fellow of CAPES (PNPD); LL and AGCM are supported by a postdoctoral fellowship from CAPES (PROTAX)