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.

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

  • 260
    downloads

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
    Yi Li, Long Gong ... Shangbang Gao
    Research Article

    Resistance to anthelmintics, particularly the macrocyclic lactone ivermectin (IVM), presents a substantial global challenge for parasite control. We found that the functional loss of an evolutionarily conserved E3 ubiquitin ligase, UBR-1, leads to IVM resistance in Caenorhabditis elegans. Multiple IVM-inhibiting activities, including viability, body size, pharyngeal pumping, and locomotion, were significantly ameliorated in various ubr-1 mutants. Interestingly, exogenous application of glutamate induces IVM resistance in wild-type animals. The sensitivity of all IVM-affected phenotypes of ubr-1 is restored by eliminating proteins associated with glutamate metabolism or signaling: GOT-1, a transaminase that converts aspartate to glutamate, and EAT-4, a vesicular glutamate transporter. We demonstrated that IVM-targeted GluCls (glutamate-gated chloride channels) are downregulated and that the IVM-mediated inhibition of serotonin-activated pharynx Ca2+ activity is diminished in ubr-1. Additionally, enhancing glutamate uptake in ubr-1 mutants through ceftriaxone completely restored their IVM sensitivity. Therefore, UBR-1 deficiency-mediated aberrant glutamate signaling leads to ivermectin resistance in C. elegans.

    1. Genetics and Genomics
    Minsoo Noh, Xiangguo Che ... Sihoon Lee
    Research Article

    Osteoporosis, characterized by reduced bone density and strength, increases fracture risk, pain, and limits mobility. Established therapies of parathyroid hormone (PTH) analogs effectively promote bone formation and reduce fractures in severe osteoporosis, but their use is limited by potential adverse effects. In the pursuit of safer osteoporosis treatments, we investigated R25CPTH, a PTH variant wherein the native arginine at position 25 is substituted by cysteine. These studies were prompted by our finding of high bone mineral density in a hypoparathyroidism patient with the R25C homozygous mutation, and we explored its effects on PTH type-1 receptor (PTH1R) signaling in cells and bone metabolism in mice. Our findings indicate that R25CPTH(1–84) forms dimers both intracellularly and extracellularly, and the synthetic dimeric peptide, R25CPTH(1–34), exhibits altered activity in PTH1R-mediated cyclic AMP (cAMP) response. Upon a single injection in mice, dimeric R25CPTH(1–34) induced acute calcemic and phosphaturic responses comparable to PTH(1–34). Furthermore, repeated daily injections increased calvarial bone thickness in intact mice and improved trabecular and cortical bone parameters in ovariectomized (OVX) mice, akin to PTH(1–34). The overall results reveal a capacity of a dimeric PTH peptide ligand to activate the PTH1R in vitro and in vivo as PTH, suggesting a potential path of therapeutic PTH analog development.