Indels, structural variation, and recombination drive genomic diversity inPlasmodium falciparum

Miles, A. et al. (2016) Indels, structural variation, and recombination drive genomic diversity inPlasmodium falciparum. Genome Research, 26(9), pp. 1288-1299. (doi:10.1101/gr.203711.115) (PMID:27531718) (PMCID:PMC5052046)

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Abstract

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 analyze using short-read sequencing 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 genome-wide, 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, being more common than SNPs and thus the dominant mode of polymorphism within the core genome. We use the high density of SNP and indel markers to analyze patterns of meiotic recombination, confirming a high rate of crossover events and providing the first estimates for the rate of non-crossover events and the length of conversion tracts. We observe several instances of meiotic recombination within copy number variants associated with drug resistance, demonstrating a mechanism whereby fitness costs associated with resistance mutations could be compensated and greater phenotypic plasticity could be acquired.

Item Type:Articles
Additional Information:This work was supported by the Wellcome Trust (090770/Z/09/Z; 098051) and Medical Research Council UK & DFID (MR/ M006212/1) and by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Research in L.R.-C.’s laboratory was supported by the Wellcome Trust (091791).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ranford-Cartwright, Dr Lisa and Mwangi, Dr Jonathan
Authors: Miles, A., Iqbal, Z., Vauterin, P., Pearson, R., Campino, S., Theron, M., Gould, K., Mead, D., Drury, E., O'Brien, J., Ruano Rubio, V., MacInnis, B., Mwangi, J., Samarakoon, U., Ranford-Cartwright, L., Ferdig, M., Hayton, K., Su, X.-z., Wellems, T., Rayner, J., McVean, G., and Kwiatkowski, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Genome Research
Publisher:Cold Spring Harbor Laboratory Press
ISSN:1088-9051
ISSN (Online):1549-5469
Published Online:16 August 2016
Copyright Holders:Copyright © 2016 Miles et al
First Published:First published in Genome Research 26(9):1288-1299
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
534421Genetic analysis of growth rates in Plasmodium falciparumLisa Ranford-CartwrightWellcome Trust (WELLCOME)091791/Z/10/ZIII - PARASITOLOGY
534422Genetic analysis of growth rates in Plasmodium falciparumLisa Ranford-CartwrightWellcome Trust (WELLCOME)091791/Z/10/AIII - PARASITOLOGY