Trypanosoma Cruzi Genome: Organization, Multi-Gene Families, Transcription, and Biological Implications

Abstract

Chagas disease caused by the parasite Trypanosoma cruzi affects millions of people. Although its first genome dates from 2005, its complexity hindered a complete assembly and annotation. However, the new sequencing methods have improved genome annotation of some strains elucidating the broad genetic diversity and complexity of this parasite. Here, we reviewed the genomic structure and regulation, the genetic diversity, and the analysis of the principal multi-gene families of the recent genomes for several strains. The telomeric and sub-telomeric regions are sites with high recombination events, the genome displays two different compartments, the core and the disruptive, and the genome plasticity seems to play a key role in the survival and the infection process. Trypanosoma cruzi (T. cruzi) genome is composed mainly of multi-gene families as the trans-sialidases, mucins, and mucin-associated surface proteins. Trans-sialidases are the most abundant genes in the genome and show an important role in the effectiveness of the infection and the parasite survival. Mucins and MASPs are also important glycosylated proteins of the surface of the parasite that play a major biological role in both insect and mammal-dwelling stages. Altogether, these studies confirm the complexity of T. cruzi genome revealing relevant concepts to better understand Chagas disease.

Keywords: Trypanosoma cruzi strain; gene expression; genome plasticity; mucins; sequencing methods; trans-sialidases.

Figure 1

Different classifications of Trypanosoma cruzi since 1999. (A) Classification of the meeting of 1999. (B) First consensus classification of 2009. (C) Second consensus classification of 2009. (D) Alternative classification proposed in 2016.

Figure 2

Transcription process of T. cruzi. RNA polymerase II produces polycistronic RNAs that are modified by trans-splicing and polyadenylation. The final mature mRNAs contain the Cap with the SL and the poly A tail. SL: spliced leader.

Figure 3

Genome copy number of the most abundant multi-gene families of T. cruzi and the B7 strain of T. cruzi marinkellei. BNEL: CL Brener Non-Esmeraldo-like; BEL: CL Brener Esmeraldo-like; DGF-1: Dispersed Gene Family 1; GP63: Glycoprotein 63; MASP: Mucin-Associated Surface Proteins; RHS: Retrotransposon Hot Spot genes.

Figure 4

First classification of TS members. Four groups were described according to their sequence similarity and functional properties. The structure and functions of each group are displayed as well as the known members with their host and parasite-stage in which they are expressed. BT: bloodstream trypomastigotes; A: amastigotes; MT: metacyclic trypomastigotes; E: epimastigotes.

Figure 5

Classification of 2011 of TS members according to a sequence cluster analysis. Each group is defined by specific motifs. Logos of each Asp-box and canonical TS motifs are displayed. Adapted from Freitas, L. M. et al., 2011 [110].

Figure 6

TS group distribution in genomes of different strains of T. cruzi and B7 strain of T. cruzi marinkellei. The percentage of each TS group is displayed. BNEL: CL Brener Non-Esmeraldo-like; BEL: CL Brener Esmeraldo-like.