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

Jose Luis Ramirez

doi:10.3390/tropicalmed5030129

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.

Highlights

Chagas disease or American trypanosomiasis is considered a zoonosis caused by the flagellate Trypanosoma cruzi
For basic researchers working on Chagas disease, it was evident that despite many years of biochemical, clinical, epidemiological and immunological studies, no new tools for the diagnostic or treatment of the disease were available, and the successful vector control measurements implemented in Latin America South-Cone countries were not as successful when applied to sylvatic environments where Reduvii bugs are not limited to domestic environments [10]
Without sharing the reductionist view held by some proponents of the Human Genome Project Initiative (HGP) [6,11], that the key to understanding all genetic diseases was in the genome, Latin America (LA) researchers decided to launch a Trypanosoma cruzi genome initiative [12] hoping to piggyback on the successful Brazilian Xyllela fastidiosa genome project [13]

Summary

A Brief Description of the Initial Findings in the CLB Genome

With the 2005 publication of the first draft [23], scientists realized how complex the T. cruzi genome was; the automated annotations revealed a much higher degree of sequence repetitions, including large multigene families, out of which the Mucin Associated Surface Protein (MASP) family was detected for the first time. In the current taxonomical classification, CLB is included in the hybrid DTU VI [4,23] Despite all these obstacles, syntenic groups were assembled, confirming previous studies [19] about the lack of synteny for some surface protein genes. A final assembly was not achieved, the genome draft presented non-syntenic blocks or islands containing highly repeated genes and blocks made up of simple genes interrupted by a few copies of retrotransposons and genes from surface protein families. A comparative analysis with the L. major and T. brucei genomes revealed that 32% of T. cruzi proteins were species-specific [23]. Another interesting feature was the expansion of the kinome (body of kinases), and the presence of enzymes necessary for meiotic recombination. One the major contributions of the 2005 genome draft was that for the first time a large scale integration of T. cruzi metabolism networks was made possible, which opened the way for whole proteome analysis [27,28] and the application of system biology approaches [29]

What is New and What is Challenging

Final Considerations