Genomic analysis of natural intra-specific hybrids among Ethiopian isolates of Leishmania donovani

Abstract

Parasites of the genus Leishmania (Kinetoplastida: Trypanosomatidae) cause widespread and devastating human diseases. Visceral leishmaniasis due to Leishmania donovani is 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 of Leishmania species, and the extant capacity for genetic exchange demonstrated in laboratory experiments. However, patterns of recombination and the evolutionary history of admixture that produced these hybrid populations remain unclear. Here, we use whole-genome sequence data to investigate Ethiopian L. donovani isolates previously characterized as hybrids by microsatellite and multi-locus sequencing. To date there is only one previous study on a natural population of Leishmania hybrids based on whole-genome sequences. We propose that these hybrids originate from recombination between two different lineages of Ethiopian L. donovani occurring 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 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 data that shows how recombination, and gene flow, shape natural populations of Leishmania.

Multiple targets of balancing selection inLeishmania donovanicomplex parasites

“…Phylogenetic analysis provides some qualitative insight to the history of these species ( Figure 1 , Panel C ). The basal position of EA2 and early-branching position of EA1 support the relative age of these populations in East Africa, as does the high genetic diversity in this region and genetic distance between these populations, consistent with previous studies (Gelanew et al , 2010(Gelanew et al , , 2014Ferreira et al , 2012;Teixeira et al , 2017;Zackay et al , 2018;Cotton et al , 2020;Franssen et al , 2020) . The high nucleotide diversity of EA1 ( Table 1 ) is reflected in the branch lengths in this clade of the phylogeny.…”

“…Although hybrids have been shown to occur between L. donovani complex populations in both East Africa and Turkey (Rogers et al , 2014;Cotton et al , 2020) , large proportions of the genetic variation within these five populations is generally derived from independent ancestry since fixation index (F ST ) values range from 0.27 to 0.90 ( Supplementary Table 7 ).…”

Evidence that interspeciesLeishmaniahybrids contribute to changes in disease pathology

“…Parasites from Africa formed three separate clusters, largely determined by their geographical isolation location, as previously reported 7 . Parasites from the north of Ethiopia and Sudan formed a cluster distinct from southern Ethiopian and Kenyan clusters with hybrid parasites between the north and south of Ethiopia forming a small intermediate cluster (highlighted in blue) 6–9,31 .…”

“…The ratios of heterozygous SNPs were plotted for all the sequenced L. donovani isolates and are shown in Figure 2B. A group of isolates originating from Ethiopia were considered separately as these were previously reported to be intra-species hybrids of two distinct L. donovani populations and therefore served as a benchmark for hybrid parasites 7,8,31 . The Ethiopian hybrid L. donovani isolates are highlighted in blue in Figure 2B.…”

Dipeptidyl peptidase III as a DNA marker to investigate epidemiology and taxonomy of Old World Leishmania species

“…Some assays are specific to certain taxonomic groups [30], others lack sensitivity [39] or specificity [34], or are only suitable for intra-specific analyses using for instance microsatellites markers [15,[40][41][42]. Increasing knowledge about evolutionary relationships is generated through genome projects [43,44] but also by resorting to well characterized markers that provide thorough supplementary data about inter and intra-species variations in clinical isolates. Such knowledge improves debated phylogeny and taxonomy [43,[45][46][47] and strengthens capacity for molecular epidemiology investigations.…”