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)
|
Text
129719.pdf - Published Version Available under License Creative Commons Attribution. 1MB |
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 > School of Infection & Immunity |
| 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 |
University Staff: Request a correction | Enlighten Editors: Update this record
Altmetric
Altmetric