Indels, structural variation, and recombination drive genomic diversity in Plasmodium falciparum

  1. Dominic Kwiatkowski1,2
  1. 1MRC Centre for Genomics and Global Health, University of Oxford, Oxford OX3 7BN, United Kingdom;
  2. 2Malaria Programme, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, United Kingdom;
  3. 3Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom;
  4. 4Bowdoin College, Brunswick, Maine 04011, USA;
  5. 5Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA;
  6. 6Department of Biochemistry, Medical School, Mount Kenya University, 01000 Thika, Kenya;
  7. 7Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom;
  8. 8Eck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556, USA;
  9. 9Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 20892-9806, USA;
  10. 10Department of Statistics, University of Oxford, Oxford OX1 3LB, United Kingdom
  1. Corresponding author: alistair.miles{at}well.ox.ac.uk

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.

Footnotes

  • [Supplemental material is available for this article.]

  • Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.203711.115.

  • Freely available online through the Genome Research Open Access option.

  • Received December 22, 2015.
  • Accepted June 28, 2016.

This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.

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