Trypanosoma cruzi Genome 15 Years Later: What Has Been Accomplished?

Abstract

On 15 July 2020 was the 15th anniversary of the Science Magazine issue that reported three trypanosomatid genomes, namely Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi. That publication was a milestone for the research community working with trypanosomatids, even more so, when considering that the first draft of the human genome was published only four years earlier after 15 years of research. Although nowadays, genome sequencing has become commonplace, the work done by researchers before that publication represented a huge challenge and a good example of international cooperation. Research in neglected diseases often faces obstacles, not only because of the unique characteristics of each biological model but also due to the lower funds the research projects receive. In the case of Trypanosoma cruzi the etiologic agent of Chagas disease, the first genome draft published in 2005 was not complete, and even after the implementation of more advanced sequencing strategies, to this date no final chromosomal map is available. However, the first genome draft enabled researchers to pick genes a la carte, produce proteins in vitro for immunological studies, and predict drug targets for the treatment of the disease or to be used in PCR diagnostic protocols. Besides, the analysis of the T. cruzi genome is revealing unique features about its organization and dynamics. In this work, I briefly summarize the actions of Latin American researchers that contributed to the first publication of the T. cruzi genome and discuss some features of the genome that may help to understand the parasite’s robustness and adaptive capabilities.

Modulation of Virulence Factors during Trypanosoma cruzi Differentiation

“…In general, only a few T. cruzi stage-specific genes encoding major surface antigens were initially described before 1999 [ 22 , 23 , 24 , 25 , 26 ]. However, the knowledge of genes involved in pathogenesis, response to environmental changes, and genetic variations among strains increased significantly after sequencing its genome [ 27 ]. The first version of the T. cruzi genome was published in 2005 using the CLBrenner strain [ 28 ] and the improved assemblies using genome sequences of two clones (TcVI and Dm28c) permitted accurate estimation of gene copy number and better annotation of surface multigene families, mucins and trans-sialidases [ 29 ].…”

Genomics and functional genomics in Leishmania and Trypanosoma cruzi: statuses, challenges and perspectives

“…Important genomic initiatives launched before 1994 were included in a comprehensive and recent review by Ramírez, 2020. (5) out the genome. (10) Wang et al (13) proposed the occurrence of three genomic compartments: (i) one corresponding to the disruptive compartment described by Berná encompassing rapidly evolving gene families associated with immune evasion; (ii) a second compartment containing gene families, such as TcSMUG, expressed in the vector stage, distributed as tandem arrays and displaying minimal diversification; and (iii) a third compartment containing all other core genes.…”

“…Important genomic initiatives launched before 1994 were included in a comprehensive and recent review by Ramírez, 2020. 5 …”

The long and winding road of reverse genetics in Trypanosoma cruzi

“…The second aspect is the availability of accurate T. cruzi genomic data, which is critical to develop gene editing strategies. The first T. cruzi genome sequence corresponding to the hybrid strain CL Brener was released in 2005, after more than a decade of effort involving laboratories and researchers from different countries [ 11 , 12 ]. Based on this genomic data, four years later a chromosomal-level assembly for each CL Brener haplotype was generated, including bacterial artificial choromosome (BAC) end sequences and synteny information from the T. brucei genome.…”