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Population Parameters Underlying an Ongoing Soft Sweep in Southeast Asian Malaria Parasites
- Source :
- Molecular Biology and Evolution
- Publication Year :
- 2016
- Publisher :
- Oxford University Press (OUP), 2016.
-
Abstract
- Multiple kelch13 alleles conferring artemisinin resistance (ART-R) are currently spreading through Southeast Asian malaria parasite populations, providing a unique opportunity to observe an ongoing soft selective sweep, investigate why resistance alleles have evolved multiple times and determine fundamental population genetic parameters for Plasmodium. We sequenced kelch13 (n = 1,876), genotyped 75 flanking SNPs, and measured clearance rate (n = 3,552) in parasite infections from Western Thailand (2001–2014). We describe 32 independent coding mutations including common mutations outside the kelch13 propeller associated with significant reductions in clearance rate. Mutations were first observed in 2003 and rose to 90% by 2014, consistent with a selection coefficient of ∼0.079. ART-R allele diversity rose until 2012 and then dropped as one allele (C580Y) spread to high frequency. The frequency with which adaptive alleles arise is determined by the rate of mutation and the population size. Two factors drive this soft sweep: (1) multiple kelch13 amino-acid mutations confer resistance providing a large mutational target—we estimate the target is 87–163 bp. (2) The population mutation parameter (Θ = 2Neμ) can be estimated from the frequency distribution of ART-R alleles and is ∼5.69, suggesting that short term effective population size is 88 thousand to 1.2 million. This is 52–705 times greater than Ne estimated from fluctuation in allele frequencies, suggesting that we have previously underestimated the capacity for adaptive evolution in Plasmodium. Our central conclusions are that retrospective studies may underestimate the complexity of selective events and the Ne relevant for adaptation for malaria is considerably higher than previously estimated.
- Subjects :
- 0301 basic medicine
Plasmodium falciparum
030106 microbiology
Population
Protozoan Proteins
Single-nucleotide polymorphism
adaptation
Biology
Southeast asian
Polymorphism, Single Nucleotide
Antimalarials
03 medical and health sciences
Gene Frequency
Mutation Rate
Effective population size
Genetics
Animals
Humans
Malaria, Falciparum
Selection, Genetic
Allele
education
rapid evolution
Molecular Biology
Allele frequency
Discoveries
Ecology, Evolution, Behavior and Systematics
education.field_of_study
drug resistance
Population size
Sequence Analysis, DNA
Thailand
Adaptation, Physiological
Artemisinins
3. Good health
Genetics, Population
030104 developmental biology
plasmodium
Evolutionary biology
Mutation
soft selective sweep
Selective sweep
effective population size
Subjects
Details
- ISSN :
- 15371719 and 07374038
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Molecular Biology and Evolution
- Accession number :
- edsair.doi.dedup.....47363c17dc5a48c6498c681ed83e171c
- Full Text :
- https://doi.org/10.1093/molbev/msw228