Multiple mitochondrial introgression events and heteroplasmy in trypanosoma cruzi revealed by Maxicircle MLST and next generation sequencing

Traub-Csekö, Y.M., Messenger, L.A., Llewellyn, M.S. , Bhattacharyya, T., Franzén, O., Lewis, M.D., Ramírez, J.D., Carrasco, H.J., Andersson, B. and Miles, M.A. (2012) Multiple mitochondrial introgression events and heteroplasmy in trypanosoma cruzi revealed by Maxicircle MLST and next generation sequencing. PLoS Neglected Tropical Diseases, 6(4), e1584. (doi: 10.1371/journal.pntd.0001584) (PMID:22506081) (PMCID:PMC3323513)

[img]
Preview
Text
112748.pdf - Published Version

1MB

Abstract

Background Mitochondrial DNA is a valuable taxonomic marker due to its relatively fast rate of evolution. In Trypanosoma cruzi, the causative agent of Chagas disease, the mitochondrial genome has a unique structural organization consisting of 20–50 maxicircles (∼20 kb) and thousands of minicircles (0.5–10 kb). T. cruzi is an early diverging protist displaying remarkable genetic heterogeneity and is recognized as a complex of six discrete typing units (DTUs). The majority of infected humans are asymptomatic for life while 30–35% develop potentially fatal cardiac and/or digestive syndromes. However, the relationship between specific clinical outcomes and T. cruzi genotype remains elusive. The availability of whole genome sequences has driven advances in high resolution genotyping techniques and re-invigorated interest in exploring the diversity present within the various DTUs. Methodology/Principal Findings To describe intra-DTU diversity, we developed a highly resolutive maxicircle multilocus sequence typing (mtMLST) scheme based on ten gene fragments. A panel of 32 TcI isolates was genotyped using the mtMLST scheme, GPI, mini-exon and 25 microsatellite loci. Comparison of nuclear and mitochondrial data revealed clearly incongruent phylogenetic histories among different geographical populations as well as major DTUs. In parallel, we exploited read depth data, generated by Illumina sequencing of the maxicircle genome from the TcI reference strain Sylvio X10/1, to provide the first evidence of mitochondrial heteroplasmy (heterogeneous mitochondrial genomes in an individual cell) in T. cruzi. Conclusions/Significance mtMLST provides a powerful approach to genotyping at the sub-DTU level. This strategy will facilitate attempts to resolve phenotypic variation in T. cruzi and to address epidemiologically important hypotheses in conjunction with intensive spatio-temporal sampling. The observations of both general and specific incidences of nuclear-mitochondrial phylogenetic incongruence indicate that genetic recombination is geographically widespread and continues to influence the natural population structure of TcI, a conclusion which challenges the traditional paradigm of clonality in T. cruzi.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Llewellyn, Professor Martin
Authors: Traub-Csekö, Y.M., Messenger, L.A., Llewellyn, M.S., Bhattacharyya, T., Franzén, O., Lewis, M.D., Ramírez, J.D., Carrasco, H.J., Andersson, B., and Miles, M.A.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2012 Messenger et al.
First Published:First published in PLoS Neglected Tropical Diseases 6(4):e1584
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record