Experimental microevolution of Trypanosoma cruzi reveals hybridization and clonal mechanisms driving rapid diversification of genome sequence and structure

  1. Gabriel Machado Matos
  2. Michael D Lewis
  3. Carlos Talavera-López
  4. Matthew Yeo
  5. Edmundo C Grisard
  6. Louisa A Messenger
  7. Michael Miles
  8. Björn Andersson  Is a corresponding author
  1. Universidade Federal de Santa Catarina, Brazil
  2. London School of Hygiene and Tropical Medicine, United Kingdom
  3. Helmholtz Zentrum München, Germany
  4. Karolinska Institute, Sweden

Abstract

Protozoa and fungi are known to have extraordinarily diverse mechanisms of genetic exchange. However, the presence and epidemiological relevance of genetic exchange in Trypanosoma cruzi, the agent of Chagas disease, has been controversial and debated for many years. Field studies have identified both predominantly clonal and sexually recombining natural populations. Two of six natural T. cruzi lineages (TcV and TcVI) show hybrid mosaicism, using analysis of single-gene locus markers. The formation of hybrid strains in vitro has been achieved and this provides a framework to study the mechanisms and adaptive significance of genetic exchange. Using whole genome sequencing of a set of experimental hybrids strains, we have confirmed that hybrid formation initially results in tetraploid parasites. The hybrid progeny showed novel mutations that were not attributable to either (diploid) parent showing an increase in amino acid changes. In long-term culture, up to 800 generations, there was a variable but gradual erosion of progeny genomes towards triploidy, yet retention of elevated copy number was observed at several core housekeeping loci. Our findings indicate hybrid formation by fusion of diploid T. cruzi, followed by sporadic genome erosion, but with substantial potential for adaptive evolution, as has been described as a genetic feature of other organisms, such as some fungi.

Data availability

The data generated in this study have been submitted to the NCBI BioProject database (https://www.ncbi.nlm.nih.gov/bioproject/) under accession number PRJNA748998.

The following data sets were generated

Article and author information

Author details

  1. Gabriel Machado Matos

    Universidade Federal de Santa Catarina, Florianopolis, Brazil
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3744-2673
  2. Michael D Lewis

    Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Carlos Talavera-López

    Helmholtz Zentrum München, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Matthew Yeo

    Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Edmundo C Grisard

    Universidade Federal de Santa Catarina, Florianopolis, Brazil
    Competing interests
    The authors declare that no competing interests exist.
  6. Louisa A Messenger

    Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Michael Miles

    Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Björn Andersson

    Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden
    For correspondence
    bjorn.andersson@ki.se
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4624-0259

Funding

Swedish Research Council, Bjorn Andersson, Michael Miles (Project Grant)

  • Gabriel Machado Matos

CAPES, Edmundo Grisard, Bjorn Andersson (Student Scholarship)

  • Björn Andersson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Antoine Claessens, University of Montpellier, France

Version history

  1. Preprint posted: October 24, 2021 (view preprint)
  2. Received: November 3, 2021
  3. Accepted: April 22, 2022
  4. Accepted Manuscript published: May 10, 2022 (version 1)
  5. Version of Record published: May 12, 2022 (version 2)
  6. Version of Record updated: May 13, 2022 (version 3)

Copyright

© 2022, Matos et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,792
    views
  • 227
    downloads
  • 8
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Gabriel Machado Matos
  2. Michael D Lewis
  3. Carlos Talavera-López
  4. Matthew Yeo
  5. Edmundo C Grisard
  6. Louisa A Messenger
  7. Michael Miles
  8. Björn Andersson
(2022)
Experimental microevolution of Trypanosoma cruzi reveals hybridization and clonal mechanisms driving rapid diversification of genome sequence and structure
eLife 11:e75237.
https://doi.org/10.7554/eLife.75237

Share this article

https://doi.org/10.7554/eLife.75237

Further reading

    1. Genetics and Genomics
    2. Neuroscience
    Céline Petitgas, Laurent Seugnet ... Serge Birman
    Research Article

    Adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) are two structurally related enzymes involved in purine recycling in humans. Inherited mutations that suppress HGPRT activity are associated with Lesch–Nyhan disease (LND), a rare X-linked metabolic and neurological disorder in children, characterized by hyperuricemia, dystonia, and compulsive self-injury. To date, no treatment is available for these neurological defects and no animal model recapitulates all symptoms of LND patients. Here, we studied LND-related mechanisms in the fruit fly. By combining enzymatic assays and phylogenetic analysis, we confirm that no HGPRT activity is expressed in Drosophila melanogaster, making the APRT homolog (Aprt) the only purine-recycling enzyme in this organism. Whereas APRT deficiency does not trigger neurological defects in humans, we observed that Drosophila Aprt mutants show both metabolic and neurobehavioral disturbances, including increased uric acid levels, locomotor impairments, sleep alterations, seizure-like behavior, reduced lifespan, and reduction of adenosine signaling and content. Locomotor defects could be rescued by Aprt re-expression in neurons and reproduced by knocking down Aprt selectively in the protocerebral anterior medial (PAM) dopaminergic neurons, the mushroom bodies, or glia subsets. Ingestion of allopurinol rescued uric acid levels in Aprt-deficient mutants but not neurological defects, as is the case in LND patients, while feeding adenosine or N6-methyladenosine (m6A) during development fully rescued the epileptic behavior. Intriguingly, pan-neuronal expression of an LND-associated mutant form of human HGPRT (I42T), but not the wild-type enzyme, resulted in early locomotor defects and seizure in flies, similar to Aprt deficiency. Overall, our results suggest that Drosophila could be used in different ways to better understand LND and seek a cure for this dramatic disease.

    1. Genetics and Genomics
    Gbolahan Bamgbose, Guillaume Bordet ... Alexei Tulin
    Research Article

    PARP-1 is central to transcriptional regulation under both normal and stress conditions, with the governing mechanisms yet to be fully understood. Our biochemical and ChIP-seq-based analyses showed that PARP-1 binds specifically to active histone marks, particularly H4K20me1. We found that H4K20me1 plays a critical role in facilitating PARP-1 binding and the regulation of PARP-1-dependent loci during both development and heat shock stress. Here, we report that the sole H4K20 mono-methylase, pr-set7, and parp-1 Drosophila mutants undergo developmental arrest. RNA-seq analysis showed an absolute correlation between PR-SET7- and PARP-1-dependent loci expression, confirming co-regulation during developmental phases. PARP-1 and PR-SET7 are both essential for activating hsp70 and other heat shock genes during heat stress, with a notable increase of H4K20me1 at their gene body. Mutating pr-set7 disrupts monomethylation of H4K20 along heat shock loci and abolish PARP-1 binding there. These data strongly suggest that H4 monomethylation is a key triggering point in PARP-1 dependent processes in chromatin.