Discussion

Chagas disease (American trypanosomiasis) and visceral leishmaniasis (VL) are major public health scourges that warrant intense research and strenuous international efforts at disease control. Astonishing progress with molecular genetics and comparative genomics is changing perceptions of the biology and molecular epidemiology of the disease agents, Trypanosoma cruzi and Leishmania. The clonal theory of parasitic protozoa considered genetic exchange to be absent or rare and of no epidemiological consequence in T. cruzi and Leishmania. On the contrary, in both instances population genetics has revealed evidence of parents and hybrids among sympatric populations. With putative parents selected from such natural populations, we have achieved experimental genetic crosses for T. cruzi and for Leishmania donovani. Experimental progeny were initially proven and characterised by a combination of targeted multilocus DNA sequencing and microsatellite analysis. Subtetraploid hybrid progeny derived from an intralineage genetic cross of T. cruzi I (TcI; DTU I) in mammalian cell culture, show progressive genome erosion over hundreds of generations of axenic growth in vitro. Crosses of L. donovani strains in two different sand fly species have yielded scores of diverse viable diploid progeny clones, indicating multiple exchange events. Whole genome sequencing allows detailed comparisons of such parents and progeny. For the first time we show that advanced genome sequencing and population genomics have resolved complex repetitive gene families of T. cruzi, giving insight into their structure, function, reassortment and post genetic exchange evolution. It is clear that genetic exchange can have a profound epidemiological impact, on the emergence and spread of virulent and drug resistant strains, on adaptation to new vectors, hosts and ecological niches. Furthermore understanding the impact of genetic exchange on genetic diversity will inform both diagnostics discovery and vaccine research. A major challenge remains to bridge the gap between such pioneering research, and the delivery of simple, proven mechanisms of controlling these neglected diseases. Funded by the EC Marie Curie EUROLEISH-NET GA No. 6426; the Swedish Research Council; the Wellcome Trust, the Ministry of Education of the Czech Republic, and institutional support.