Genomic analysis of natural intra-specific hybrids among Ethiopian isolates ofLeishmania donovani
Authors: Cotton James A. , Durrant Caroline , Franssen Susanne U. , Gelanew Tesfaye , Hailu Asrat , Mateus David , Sanders Mandy J. , Berriman Matthew , Volf Petr , Miles Michael A. , Yeo Matthew 
Published: January 2019

Parasites of the genusLeishmania(Kinetoplastida: Trypanosomatidae) cause widespread and devastating human diseases, ranging from self-healing but disfiguring cutaneous lesions to destructive mucocutaneous presentations or usually fatal visceral disease. Visceral leishmaniasis due toLeishmania donovaniis endemic in Ethiopia where it has also been responsible for major epidemics. The presence of hybrid genotypes has been widely reported in surveys of natural populations, genetic variation reported in a number ofLeishmaniaspecies, and the extant capacity for genetic exchange demonstrated in laboratory experiments. However, patterns of recombination and evolutionary history of admixture that produced these hybrid populations remain unclear, as most of the relevant literature examines only a limited number (typically fewer than 10) genetic loci. Here, we use whole-genome sequence data to investigate EthiopianL. donovaniisolates previously characterised as hybrids by microsatellite and multi-locus sequencing. To date there is only one previous study on a natural population ofLeishmaniahybrids, based on whole-genome sequence. The current findings demonstrate important differences. We propose hybrids originate from recombination between two different lineages of EthiopianL. donovanioccurring in the same region. Patterns of inheritance are more complex than previously reported with multiple, apparently independent, origins from similar parents that include backcrossing with parental types. Analysis indicates that hybrids are representative of at least three different histories. Furthermore, isolates were highly polysomic at the level of chromosomes with startling differences between parasites recovered from a recrudescent infection from a previously treated individual. The results demonstrate that recombination is a significant feature of natural populations and contributes to the growing body of evidence describing how recombination, and gene flow, shape natural populations ofLeishmania.

Author Summary

Leishmaniasis is a spectrum of diseases caused by the protozoan parasiteLeishmania. It is transmitted by sandfly insect vectors and is responsible for an enormous burden of human suffering. In this manuscript we examineLeishmaniaisolates from Ethiopia that cause the most serious form of the disease, namely visceral leishmaniasis, which is usually fatal without treatment. Historically the general view was that such parasites reproduce clonally, so that their progeny are genetically identical to the founding cells. This view has changed over time and it is increasingly clear that recombination between genetically differentLeishmaniaparasites occurs. The implication is that new biological traits such as virulence, resistance to drug treatments or the ability to infect new species of sandfly could emerge. The frequency and underlying mechanism of such recombination in natural isolates is poorly understood. Here we perform a detailed whole genome analysis on a cohort of hybrid isolates from Ethiopia together with their potential parents to assess the genetic nature of hybrids in more detail. Results reveal a complex pattern of mating and inbreeding indicative of multiple mating events that has likely shaped the epidemiology of the disease agent. We also show that some hybrids have very different relative amounts of DNA (polysomy) the implications of which are discussed. Together the results contribute to a fuller understanding of the nature of genetic recombination in natural populations ofLeishmania.