Original Publication Date
Parasites & Vectors
Date of Submission
Proline racemase (PRAC) enzymes of Trypanosoma cruzi (TcPRAC), the agent of Chagas disease, and Trypanosoma vivax (TvPRAC), the agent of livestock trypanosomosis, have been implicated in the B-cells polyclonal activation contributing to immunosuppression and the evasion of host defences. The similarity to prokaryotic PRAC and the absence in Trypanosoma brucei andTrypanosoma congolense have raised many questions about the origin, evolution, and functions of trypanosome PRAC (TryPRAC) enzymes.
We identified TryPRAC homologs as single copy genes per haploid genome in 12 of 15Trypanosoma species, including T. cruzi and T. cruzi marinkellei, T. dionisii, T. erneyi, T. rangeli, T. conorhini and T. lewisi, all parasites of mammals. Polymorphisms in TcPRAC genes matched T. cruzi genotypes: TcI-TcIV and Tcbat have unique genes, while the hybrids TcV and TcVI containTcPRACA and TcPRACB from parental TcII and TcIII, respectively. PRAC homologs were identified in trypanosomes from anurans, snakes, crocodiles, lizards, and birds. Most trypanosomes have intact PRAC genes. T. rangeli possesses only pseudogenes, maybe in the process of being lost. T. brucei, T. congolense and their allied species, except the more distantly related T. vivax, have completely lost PRAC genes.
The genealogy of TryPRAC homologs supports an evolutionary history congruent with theTrypanosoma phylogeny. This finding, together with the synteny of PRAC loci, the relationships with prokaryotic PRAC inferred by taxon-rich phylogenetic analysis, and the absence in trypanosomatids of any other genera or in bodonids or euglenids suggest that a common ancestor of Trypanosoma gained PRAC gene by a single and ancient horizontal gene transfer (HGT) from a Firmicutes bacterium more closely related to Gemella and other species of Bacilli than toClostridium as previously suggested. Our broad phylogenetic study allowed investigation ofTryPRAC evolution over long and short timescales. TryPRAC genes diverged to become species-specific and genotype-specific for T. cruzi and T. rangeli, with resulting genealogies congruent with those obtained using vertically inherited genes. The inventory of TryPRAC genes described here is the first step toward the understanding of the roles of PRAC enzymes in trypanosomes differing in life cycles, virulence, and infection and immune evasion strategies.
Copyright © 2015 Caballero et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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VCU Microbiology and Immunology Publications
Table containing the isolates of T. cruzi and T. rangeli and respective host species, geographic origin and lineages, and Genbank accession numbers of their respective PRAC gene sequences.
s13071-015-0829-y-s2.pdf (189 kB)
Genbank accession numbers of gGAPDH gene sequences included in the Figure 2 B.
s13071-015-0829-y-s3.pdf (41 kB)
(A)Network genealogy of entire PRAC amino-acid sequences from T. cruzi isolates of different DTUs.
s13071-015-0829-y-s4.pdf (164 kB)
Alignment of predicted amino acid sequences of PRAC pseudogenes from T. rangeli isolates of all phylogenetic lineages (TrA-TrE). Essential motifs (MCGH and MIII) are in green, active site in red (SPCGT), R1, R2 and R3 in blue and Cys91/267 in yellow.
s13071-015-0829-y-s5.pdf (191 kB)
Maximum likelihood phylogeny of 2,530 PRAC-like protein sequences (Figure 5 A) displayed as rectangular phylogram.
s13071-015-0829-y-s6.pdf (168 kB)
Genbank acession numbers of 2,530 PRAC-like family genes from prokaryotes and eukaryotes retrieved from full NCBI NR database and included in the Figure 5 A.
s13071-015-0829-y-s7.pdf (1116 kB)
Genbank accession numbers of 303 prokaryotic PRAC-like genes closest related to TryPRAC genes retrieved from full NCBI NR database and included in the Figure 5B.