Abstract
Genetic exchange among disease-causing micro-organisms can generate progeny that combine different pathogenic traits. Though sexual reproduction has been described in trypanosomes, its impact on the epidemiology of Human African Trypanosomiasis (HAT) remains controversial. However, human infective and non-human infective strains of Trypanosoma brucei circulate in the same transmission cycles in HAT endemic areas in subsaharan Africa, providing the opportunity for mating during the developmental cycle in the tsetse fly vector. Here we investigated inheritance among progeny from a laboratory cross of T. brucei and then applied these insights to genomic analysis of field-collected isolates to identify signatures of past genetic exchange. Genomes of two parental and four hybrid progeny clones with a range of DNA contents were assembled and analysed by k-mer and single nucleotide polymorphism (SNP) frequencies to determine heterozygosity and chromosomal inheritance. Variant surface glycoprotein (VSG) genes and kinetoplast (mitochondrial) DNA maxi- and minicircles were extracted from each genome to examine how each of these components was inherited in the hybrid progeny. The same bioinformatic approaches were applied to an additional 37 genomes representing the diversity of T. brucei in subsaharan Africa and T. evansi. SNP analysis provided evidence of crossover events affecting all 11 pairs of megabase chromosomes and demonstrated that polyploid hybrids were formed post-meiotically and not by fusion of the parental diploid cells. VSGs and kinetoplast DNA minicircles were inherited biparentally, with approximately equal numbers from each parent, whereas maxicircles were inherited uniparentally. Extrapolation of these findings to field isolates allowed us to distinguish clonal descent from hybridization by comparing maxicircle genotype to VSG and minicircle repertoires. Discordance between maxicircle genotype and VSG and minicircle repertoires indicated inter-lineage hybridization. Significantly, some of the hybridization events we identified involved human infective and non-human infective trypanosomes circulating in the same geographic areas.
Highlights
Sexual reproduction allows the mixing of genes from different individuals with formation of hybrid progeny
We investigated the inheritance of two other features of trypanosomes: the large family of variant surface glycoprotein (VSG) genes, and the mitochondrial DNA
While most isolates shared few VSGs or minicircles, a group of mostly human-infective strains from Uganda had a large proportion of their repertoires in common. Most of these trypanosomes were probably related by clonal descent, but we identified that some were hybrids by the mismatch between their maxicircle genotype and their VSG and minicircle repertoires
Summary
Sexual reproduction allows the mixing of genes from different individuals with formation of hybrid progeny. For microbial pathogens this is important, as new combinations of traits such as drug resistance or virulence may be generated, potentially leading to more pathogenic strains and outbreaks of disease. Tsetse-transmitted trypanosomes such as Trypanosoma brucei and T. congolense are parasitic protists that cause severe human and livestock diseases in tropical Africa. During their developmental cycles in the tsetse fly, these trypanosomes undergo complex cycles of differentiation and proliferation in the fly’s alimentary tract, ending up as infective metacyclics that are transmitted to the host via the fly’s saliva. Polyploid hybrids are frequently found in experimental crosses of Leishmania spp. [10,11,12,13,14]; of 24 hybrid clones from an in vitro cross of L. tropica, 19 (79%) were 3N or 4N [15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
