Genome variation and meiotic recombination in Plasmodium falciparum: insights from deep sequencing of genetic crosses
Alistair Miles, Zamin Iqbal, Paul Vauterin, Richard Pearson, Susana Campino, Michel Theron, Kelda Gould, Daniel Mead, Eleanor Drury, John O’Brien, Valentin Ruano Rubio, Bronwyn MacInnis, Jonathan Mwangi, Upeka Samarakoon, Lisa Ranford-Cartwright, Michael Ferdig, Karen Hayton, Xinzhuan Su, Thomas Wellems, Julian Rayner, Gil McVean, Dominic Kwiatkowski
The malaria parasite Plasmodium falciparum has a great capacity for evolutionary adaptation to evade host immunity and develop drug resistance. Current understanding of parasite evolution is impeded by the fact that a large fraction of the genome is either highly repetitive or highly variable, and thus difficult to analyse using short read technologies. Here we describe a resource of deep sequencing data on parents and progeny from genetic crosses, which has enabled us to perform the first integrated analysis of SNP, INDEL and complex polymorphisms, using Mendelian error rates as an indicator of genotypic accuracy. These data reveal that INDELs are exceptionally abundant and the dominant mode of polymorphism within the core genome. We analyse patterns of meiotic recombination, including the relative contribution of crossover and non-crossover events, and we observe several instances of recombination that modify copy number variants associated with drug resistance. We describe a novel web application that allows these data to be explored in detail.