Widespread, focal copy number variations (CNV) and whole chromosome aneuploidies in Trypanosoma cruzi strains revealed by array comparative genomic hybridization

Abstract

BackgroundTrypanosoma cruzi is a protozoan parasite and the etiologic agent of Chagas disease, an important public health problem in Latin America. T. cruzi is diploid, almost exclusively asexual, and displays an extraordinarily diverse population structure both genetically and phenotypically. Yet, to date the genotypic diversity of T. cruzi and its relationship, if any, to biological diversity have not been studied at the whole genome level.ResultsIn this study, we used whole genome oligonucleotide tiling arrays to compare gene content in biologically disparate T. cruzi strains by comparative genomic hybridization (CGH). We observed that T. cruzi strains display widespread and focal copy number variations (CNV) and a substantially greater level of diversity than can be adequately defined by the current genetic typing methods. As expected, CNV were particularly frequent in gene family-rich regions containing mucins and trans-sialidases but were also evident in core genes. Gene groups that showed little variation in copy numbers among the strains tested included those encoding protein kinases and ribosomal proteins, suggesting these loci were less permissive to CNV. Moreover, frequent variation in chromosome copy numbers were observed, and chromosome-specific CNV signatures were shared by genetically divergent T. cruzi strains.ConclusionsThe large number of CNV, over 4,000, reported here uphold at a whole genome level the long held paradigm of extraordinary genome plasticity among T. cruzi strains. Moreover, the fact that these heritable markers do not parse T. cruzi strains along the same lines as traditional typing methods is strongly suggestive of genetic exchange playing a major role in T. cruzi population structure and biology.

Adaptive mechanisms in pathogens: universal aneuploidy in Leishmania

“…The same is true for the related parasite Trypanosoma cruzi that has extraordinary diversity within hosts [31]. Comparative genomic hybridization of different T. cruzi strains has illustrated frequent variation in chromosome copy numbers [32].…”

Is Predominant Clonal Evolution a Common Evolutionary Adaptation to Parasitism in Pathogenic Parasitic Protozoa, Fungi, Bacteria, and Viruses?

“…b Llewellyn et al (2009aLlewellyn et al ( d , 2009bLlewellyn et al ( , 2011 b ) Sarkar and Guttman (2004) b,e Lymbery and Thompson (2012) c Sheppard et al (2010) b Minning et al (2011) a,b Smyth and Robinson (2010) b,e Miotto et al (2013) …”

“…'far from being a clonal species' (Coscoll a et al, 2011), 'extensive genetic exchange' (Caugant and Maiden, 2009), 'gross' incongruences (between phylogenetic trees) (Messenger et al, 2012), 'widespread genetic exchange' Ramírez and Lllewellyn, 2014), 'intense lateral exchange of genetic information' (Ramírez and Llewellyn, 2015), 'genetic exchange is a fairly common phenomenon' (Lima et al, 2014), 'genetic exchange playing a major role in T. cruzi population structure' (Minning et al, 2011), and others. It is impossible to totally discard such expressions in the scientific literature.…”

“…In this species, there is LD: (1) among MLEE loci (Tibayrenc et al, 1981(Tibayrenc et al, , 1986 and (2) between different kinds of markers: nuclear and mitochondrial polymorphisms (de Freitas et al, 2006;Machado and Ayala, 2001;Ramírez et al, 2011;Spotorno et al, 2008), random amplified polymorphic DNA (RAPD) and MLEE (Tibayrenc et al, 1993;Brisse et al, 2000), microsatellite polymorphism and DNA content , neutral markers and strongly selected antigen genes (Lima et al, 2012;Rozas et al, 2007), as well as neutral genetic markers and the protein polymorphism revealed by proteomic analysis (Telleria et al, 2010). Although Minning et al (2011) considered that their data suggested 'genetic exchange playing a major role in T. cruzi population structure', in their study, there is an obvious LD between CNV polymorphism and near-clade classification: all near-clade TCI strains clearly group together, as do all non-TCI strains (see their Fig. 3).…”

“…In Leishmania donovani (included in the Leishmania infantum complex), there is a strong LD between single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) (Downing et al, 2011;Minning et al, 2011).). In the same species, high-resolution typing by WGS/SNP of 204 clinical isolates from Nepal and India (Imamura et al, 2016) reveals a remarkable case of RD pattern.…”