MonomorphicTrypanozoon: towards reconciling phylogeny and pathologies

Abstract

Trypanosoma brucei evansi and Trypanosoma brucei equiperdum are animal infective trypanosomes conventionally classified by their clinical disease presentation, mode of transmission, host range, kDNA composition and geographic distribution. Unlike other members of the subgenus Trypanozoon, they are non-tsetse transmitted and predominantly morphologically uniform (monomorphic) in their mammalian host. Their classification as independent species or subspecies has been long debated and genomic studies have found that isolates within T. b. evansi and T. b. equiperdum have polyphyletic origins. Since current taxonomy does not fully acknowledge these polyphyletic relationships, we re-analysed publicly available genomic data to carefully define each clade of monomorphic trypanosome. This allowed us to identify, and account for, lineage specific variation. We included a recently published isolate, IVM-t1, which was originally isolated from the genital mucosa of a horse with dourine and typed as T. equiperdum. Our analyses corroborate previous studies in identifying at least four distinct monomorphic T. brucei clades. We also found clear lineage specific variation in the selection efficacy and heterozygosity of the monomorphic lineages, supporting their distinct evolutionary histories. The inferred evolutionary position of IVM-t1 suggests its reassignment to the T. b. evansi type B clade, challenging the relationship between the Trypanozoon species, the infected host, mode of transmission and the associated pathological phenotype. The analysis of IVM-t1 also provides the first evidence of the expansion of T. b. evansi type B, or a 5th monomorphic lineage represented by IVM-t1, outside of Africa, with important possible implications for disease diagnosis.

PAG3 promotes the differentiation of bloodstream forms in Trypanosoma brucei and reveals the evolutionary relationship among the Trypanozoon trypanosomes

“…From our data, the complete lack of PAG3 combined with the monomorphic phenotype found in all strains of T. evansi, that we looked at, and some strains of T. equiperdum suggest a strong link between the function of this gene and differentiation of the bloodstream forms of Trypanozoon parasites. A recent analysis of the relationships between T. brucei, T. evansi and T. equiperdum, using genome sequencing data, demonstrated the presence of two clades of T. evansi (Type A and B) (Cuypers et al, 2017;Oldrieve et al, 2021). A detailed look at a Type B strain (MU10) in the NCBI Sequence Read Archive, we found that the PAG3 gene is probably present but appears to have indels and frameshifts which may possibly render it inactive.…”

“…This might support the notion that the genotypes of T. equiperdum have polyphyletic origins. This is supported by the studies of Oldrieve et al (2021) who demonstrated, by genome analysis, that there is indeed more than one clade of T. equiperdum in the strains that they look at. Unfortunately, their strains do not correspond to our strains.…”

“…This view is supported by the latest reported isolate of T. equiperdum (IVM-t1) from Mongolia (Suganuma et al, 2016). This isolate has been found to be a lost link from T. brucei to a distinct type of T. evansi (Davaasuren et al, 2019;Oldrieve et al, 2021), and is characterized by possessing a possible frameshifted PAG3 gene.…”

“…On the other hand, PAG3 was found to be lost in all of the type A strains of T. evansi we examined. However, the type B strains reported recently (Oldrieve et al, 2021) may also have a possible frameshifted PAG3 as found in IVM-t1. These may support the hypothesis that T. evansi is likely to have polyphyletic origins (Njiru et al, 2006).…”

“…The very precise deletion of this segment of PAG3 tends to suggest a common evolutionary origin and a possible interpretation is that the tested T. evansi and the PAG3 deficient T. equiperdum strains are monophyletic. Interestingly, in a recent study (Oldrieve et al, 2021) reports the presence of another clade of T. evansi (type B) which also contains a recently identified T. equiperdum strain (IVM-t1). We did not have these strains to look at in our study but the genome of the latter strain has been recently sequenced and there is also available sequence data from the MU10 strain (a type B T. evansi).…”