Abstract

BackgroundTransmission of the malaria parasite Plasmodium falciparum from humans to the mosquito vector requires differentiation of a sub-population of asexual forms replicating within red blood cells into non-dividing male and female gametocytes. The nature of the molecular mechanism underlying this key differentiation event required for malaria transmission is not fully understood.MethodsWhole genome sequencing was used to examine the genomic diversity of the gametocyte non-producing 3D7-derived lines F12 and A4. These lines were used in the recent detection of the PF3D7_1222600 locus (encoding PfAP2-G), which acts as a genetic master switch that triggers gametocyte development.ResultsThe evolutionary changes from the 3D7 parental strain through its derivatives F12 (culture-passage derived cloned line) and A4 (transgenic cloned line) were identified. The genetic differences including the formation of chimeric var genes are presented.ConclusionA genomics resource is provided for the further study of gametocytogenesis or other phenotypes using these parasite lines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1254-1) contains supplementary material, which is available to authorized users.

Highlights

  • Transmission of the malaria parasite Plasmodium falciparum from humans to the mosquito vector requires differentiation of a sub-population of asexual forms replicating within red blood cells into non-dividing male and female gametocytes

  • A comprehensive analysis is presented of the three P. falciparum genomes that were previously used as part of a study to determine that the transcriptional regulator AP2-G is a key determinant of sexual differentiation

  • These cloned lines have been in long-term culture, so as expected several Single nucleotide polymorphisms (SNPs), indels, structural variants and some new chimeric var genes were identified

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Summary

Introduction

Transmission of the malaria parasite Plasmodium falciparum from humans to the mosquito vector requires differentiation of a sub-population of asexual forms replicating within red blood cells into non-dividing male and female gametocytes. Malaria control efforts focus mainly on the application of insecticides to kill the mosquito vector, and on the use of anti-malarial drugs that prevent the parasite from replicating/proliferating in the liver or red blood cell stages in the host. These tools reduce the prevalence of infection, but to reach elimination additional efforts will be required to interrupt transmission. Interventions that disrupt the switch to sexual development that occurs in the human host could

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