Caballero Zuleima C, Costa-Martins Andre G, Ferreira Robson C, P Alves João M, Serrano Myrna G, Camargo Erney P, Buck Gregory A, Minoprio Paola, G Teixeira Marta M
Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, 05508-900, Brazil.
Instituto de Investigaciones Científicas y Servicios de Alta Tecnología-AIP (INDICASAT-AIP), Ciudad del Saber, Clayon, Panamá.
Parasit Vectors. 2015 Apr 12;8:222. doi: 10.1186/s13071-015-0829-y.
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 and Trypanosoma 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 15 Trypanosoma 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 contain TcPRACA 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 the Trypanosoma 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 to Clostridium as previously suggested. Our broad phylogenetic study allowed investigation of TryPRAC 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.
恰加斯病病原体克氏锥虫（TcPRAC）和家畜锥虫病病原体活泼锥虫（TvPRAC）的脯氨酸消旋酶（PRAC），与B细胞多克隆激活有关，这会导致免疫抑制和宿主防御的逃避。与原核PRAC的相似性以及在布氏锥虫和刚果锥虫中不存在该酶，引发了许多关于锥虫PRAC（TryPRAC）酶的起源、进化和功能的问题。
我们在15种锥虫中的12种单倍体基因组中鉴定出TryPRAC同源物为单拷贝基因，这些锥虫包括克氏锥虫、克氏锥虫马林凯莱变种、迪氏锥虫、埃尔内伊锥虫、兰氏锥虫、科诺里锥虫和刘易斯锥虫，均为哺乳动物寄生虫。克氏锥虫PRAC基因中的多态性与克氏锥虫基因型相匹配：TcI - TcIV和Tcbat具有独特的基因，而杂交种TcV和TcVI分别包含来自亲本TcII和TcIII的TcPRACA和TcPRACB。在来自无尾两栖类、蛇、鳄鱼、蜥蜴和鸟类的锥虫中也鉴定出了PRAC同源物。大多数锥虫具有完整的PRAC基因。兰氏锥虫仅拥有假基因，可能正处于丢失过程中。布氏锥虫、刚果锥虫及其相关物种，除了亲缘关系较远的活泼锥虫外，已完全丢失PRAC基因。
TryPRAC同源物的谱系支持了与锥虫系统发育一致的进化历史。这一发现，连同PRAC基因座的共线性、通过丰富分类群的系统发育分析推断出的与原核PRAC的关系，以及在其他属的锥虫、波豆虫或眼虫中不存在该酶，表明锥虫的一个共同祖先通过一次古老的水平基因转移（HGT）从一种与孪生球菌和其他芽孢杆菌属物种关系比与梭菌属更密切的厚壁菌门细菌获得了PRAC基因，而不是如先前所认为的那样来自梭菌属。我们广泛的系统发育研究允许在长和短时间尺度上研究TryPRAC的进化。TryPRAC基因发生分歧，成为克氏锥虫和兰氏锥虫物种特异性和基因型特异性的基因，其产生的谱系与使用垂直遗传基因获得的谱系一致。此处描述的TryPRAC基因清单是理解PRAC酶在生命周期、毒力、感染和免疫逃避策略不同的锥虫中的作用的第一步。
