Population Structure of Leishmania using POPSICLE reveals extensive dichotomy in zygosity and discloses the role of sex in diversity of the parasite

Abstract

Mosaic aneuploidy prevalent in organisms such as Leishmania and Fungi and in genomes of some neurological disorders and cancers manifest as non-integer haplotypes due to heterogeneity in somy across a population of cells. Thus, the tools designed for strictly haploid or diploid genomes are insufficient to study them. We addressed this issue by upgrading our population genetics tool POPSICLE for aneuploid genomes and studied the population structure of 50 strains of Leishmania to understand genetic diversity and the sexual strategies that predispose to that diversity. Leishmania showed enormous diversity but a dichotomic nature of extreme zygosities. To understand this dichotomy, we specifically studied two species, L. tropica that contained strains with both hetero and homozygosities and L. major that were mainly homozygous. The homozygosity in L. tropica was a consequence of extreme inbreeding while heterozygosity was due to recent hybridizations involving two different genotypes. In contrast, L. major also contained two different genotypes and products of extreme inbreeding but no recent hybridizations. The heterozygous strains of L. tropica that were geographically isolated from the homozygous strains were F1 hybrids that appeared sterile to each other while those in proximity to the homozygous strains were outcrosses involving multiple cycles of hybridization indicating their mating preference with homozygous strains. Development of POPSICLE for aneuploid genomes offers a unique tool for determining the shared ancestries and in reinforcing sex as one of the driving mechanisms for speciation as demonstrated for Leishmania. POPSICLE is a Java based utility available for free download at https://popsicleadmixture.sourceforge.io/