Genome diversity of Leishmania aethiopica

Abstract

Leishmania aethiopica is a zoonotic Old World parasite transmitted by Phlebotomine sand flies and causing cutaneous leishmaniasis in Ethiopia and Kenya. Despite a range of clinical manifestations and a high prevalence of treatment failure, L. aethiopica is one of the most neglected species of the Leishmania genus in terms of scientific attention. Here, we explored the genome diversity of L. aethiopica by analyzing the genomes of twenty isolates from Ethiopia. Phylogenomic analyses identified two strains as interspecific hybrids involving L. aethiopica as one parent and L. donovani and L. tropica respectively as the other parent. High levels of genome-wide heterozygosity suggest that these two hybrids are equivalent to F1 progeny that propagated mitotically since the initial hybridization event. Analyses of allelic read depths further revealed that the L. aethiopica - L. tropica hybrid was diploid and the L. aethiopica - L. donovani hybrid was triploid, as has been described for other interspecific Leishmania hybrids. When focusing on L. aethiopica, we show that this species is genetically highly diverse and consists of both asexually evolving strains and groups of recombining parasites. A remarkable observation is that some L. aethiopica strains showed an extensive loss of heterozygosity across large regions of the nuclear genome, which likely arose from gene conversion/mitotic recombination. Hence, our prospection of L. aethiopica genomics revealed new insights into the genomic consequences of both meiotic and mitotic recombination in Leishmania.

Keywords: asexual evolution; hybridization; interspecific hybrid; loss-of-heterozygosity (LOH); population genomics; triploid hybrid.

Figure 1

(A) Phylogenetic network based on SNPs called across 36 genomes of L. aethiopica, the L. donovani species complex, L. major and L. tropica. (B) Number of heterozygous sites versus number of homozygous sites for each of the 36 Leishmania genomes. (C) Phylogenetic network based on SNPs called in the last 700kb of chromosome 34 and the first 300kb in chromosome 22. Blue dot indicates the position of the interspecific L. aethiopica - L. tropica hybrid L86.

Figure 2

Loss-Of-Heterozygosity regions (red bars) in each of the 20 L. aethiopica genomes across the 36 chromosomes.

Figure 3

Population genomic diversity and structure of L. aethiopica. (A) Bar plots depicting ancestral components as inferred by ADMIXTURE for K = 2 and K = 3 populations, based on 85,725 SNPs. (B) Phylogenetic network based on uncorrected p-distances among 18 L. aethiopica genomes genotyped at 277,156 bi-allelic SNPs. Colored branches and tip labels correspond to the inferred populations by ADMIXTURE at K=3. (C) Linkage decay plot for 1561-80, 68-83, 169-83, 32-83 and 117-82 controlling for spatio-temporal Wahlund effects (see methods). (D) Fis distribution after correction for spatio-temporal Wahlund effects for 1561-80, 68-83, 169-83, 32-83 and 117-82. The solid line represents the mean Fis values (0.027) while the dashed lines represent the standard deviation (± 0.47).

Figure 4

Somy variation across 36 chromosomes for the 28 Leishmania genomes sequenced in this study. Box 1 highlights genomes that are nearly diploid, box 2 highlights genomes with a trisomic chromosome 1 and box 3 highlights genomes showing high somy variability (see text).