title: Genome-wide SNP and microsatellite variation illuminate population-level epidemiology in the Leishmania donovani species complex.
abstract: The species of the Leishmania donovani species complex cause visceral leishmaniasis, a debilitating infectious disease transmitted by sandflies. Understanding molecular changes associated with population structure in these parasites can help unravel their epidemiology and spread in humans. In this study, we used a panel of standard microsatellite loci and genome-wide SNPs to investigate population-level diversity in L. donovani strains recently isolated from a small geographic area spanning India, Bihar and Nepal, and compared their variation to that found in diverse strains of the L. donovani complex isolates from Europe, Africa and Asia. Microsatellites and SNPs could clearly resolve the phylogenetic relationships of the strains between continents, and microsatellite phylogenies indicated that certain older Indian strains were closely related to African strains. In the context of the anti-malaria spraying campaigns in the 1960s, this was consistent with a pattern of episodic population size contractions and clonal expansions in these parasites that was supported by population history simulations. In sharp contrast to the low resolution provided by microsatellites, SNPs retained a much more fine-scale resolution of population-level variability to the extent that they identified four different lineages from the same region one of which was more closely related to African and European strains than to Indian or Nepalese ones. Joining results of in vitro testing the antimonial drug sensitivity with the phylogenetic signals from the SNP data highlighted protein-level mutations revealing a distinct drug-resistant group of Nepalese and Indian L. donovani. This study demonstrates the power of genomic data for exploring parasite population structure. Furthermore, markers defining different genetic groups have been discovered that could potentially be applied to investigate drug resistance in clinical Leishmania strains.
authors: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK. Tim.Downing@sanger.ac.uk
authors: Tim
authors: T
authors: Downing
authors: Olivia
authors: O
authors: Stark
authors: Manu
authors: M
authors: Vanaerschot
authors: Hideo
authors: H
authors: Imamura
authors: Mandy
authors: M
authors: Sanders
authors: Saskia
authors: S
authors: Decuypere
authors: Simonne
authors: S
authors: de Doncker
authors: Ilse
authors: I
authors: Maes
authors: Suman
authors: S
authors: Rijal
authors: Shyam
authors: S
authors: Sundar
authors: Jean-Claude
authors: JC
authors: Dujardin
authors: Matthew
authors: M
authors: Berriman
authors: Gabriele
authors: G
authors: Schönian
mesh_terms: D000349:Africa; D000965:Antimony / Q000494:pharmacology; D001208:Asia; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance; D005060:Europe; D056426:Genetic Loci; D018503:Genome, Protozoan; D005838:Genotype; D006801:Humans; D007194:India; D007893:Leishmania donovani / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D007898:Leishmaniasis, Visceral / Q000453:epidemiology / Q000469:parasitology; D018895:Microsatellite Repeats; D010802:Phylogeny; D058974:Phylogeography; D020641:Polymorphism, Single Nucleotide
chemical_list: D016054:DNA, Protozoan; D000965:Antimony