Genome variation and meiotic recombination in Plasmodium falciparum: insights from deep sequencing of genetic crosses
| Autor: | Zamin Iqbal, Michel Theron, Paul Vauterin, Kelda Gould, Susana Campino, Julian C. Rayner, Eleanor Drury, Daniel Mead, Upeka Samarakoon, Bronwyn MacInnis, Karen Hayton, Xin-zhuan Su, Michael T. Ferdig, Lisa C. Ranford-Cartwright, Thomas E. Wellems, Alistair Miles, Jonathan M. Mwangi, Gil McVean, Richard D. Pearson, Dominic P. Kwiatkowski, Valentin Ruano Rubio, John O'Brien |
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| Rok vydání: | 2015 |
| Předmět: |
Genetics
0303 health sciences Genomics Single-nucleotide polymorphism Biology Genome Deep sequencing 3. Good health 03 medical and health sciences symbols.namesake 0302 clinical medicine Genotype Mendelian inheritance symbols Copy-number variation Indel 030217 neurology & neurosurgery 030304 developmental biology |
| Popis: | 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 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 analyse 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 recombination that modify 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. We describe a novel web application that allows these data to be explored in detail. |
| Databáze: | OpenAIRE |
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