ArticlePLoS genetics2019
Genetic mapping of fitness determinants across the malaria parasite Plasmodium falciparum life cycle.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- Impact of intensive control on malaria population genomics under elimination settings in Southeast Asia.Nature microbiology · 2026Article
- Towards an evolutionary baseline model ofbioRxiv : the preprint server for biology · 2025Article
- Target gene mutation discovery and amplicon sequencing for evaluating maduramicin resistance in Eimeria tenella.Communications biology · 2025Article
- Characterizing Plasmodium falciparum genetic diversity and complexity of infections in clinical malaria infections in Western and Coastal Kenya using the poly-alpha microsatellite marker.Malaria journal · 2025Article
- In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025Review
- MalKinID: A classification model for identifying malaria parasite genealogical relationships using identity-by-descent.Genetics · 2025Article
- Molecular dissection of laboratory contamination between two schistosome populations.Parasites & vectors · 2024Article
- Plasmodium falciparum genetic diversity and multiplicity of infection among asymptomatic and symptomatic malaria-infected individuals in Uganda.Tropical medicine and health · 2024Article
- Rapid phenotypic and genotypic change in a laboratory schistosome population.Research square · 2024Article
- Rapid phenotypic and genotypic change in a laboratory schistosome population.bioRxiv : the preprint server for biology · 2024Article
- AmBio · 2024Article
- Mapping the genomic landscape of multidrug resistance inScience advances · 2023Article
- Cultivation of Asexual Intraerythrocytic Stages ofPathogens (Basel, Switzerland) · 2023Review
- Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1.Nature microbiology · 2023Article
- Assessment of artemisinin tolerance in Plasmodium falciparum clinical isolates in children with uncomplicated malaria in Ghana.Malaria journal · 2023Article
- Bulk segregant linkage mapping for rodent and human malaria parasites.Parasitology international · 2022Review
- Article
- AiScience · 2022Article
- Nutrient Limitation Magnifies Fitness Costs of Antimalarial Drug Resistance Mutations.Antimicrobial agents and chemotherapy · 2022Article
- Optimizing bulk segregant analysis of drug resistance usingiScience · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Determining the genetic basis of fitness is central to understanding evolution and transmission of microbial pathogens. In human malaria parasites (Plasmodium falciparum), most experimental work on fitness has focused on asexual blood stage parasites, because this stage can be easily cultured, although the transmission of malaria requires both female Anopheles mosquitoes and vertebrate hosts. We explore a powerful approach to identify the genetic determinants of parasite fitness across both invertebrate and vertebrate life-cycle stages of P. falciparum. This combines experimental genetic crosses using humanized mice, with selective whole genome amplification and pooled sequencing to determine genome-wide allele frequencies and identify genomic regions under selection across multiple lifecycle stages. We applied this approach to genetic crosses between artemisinin resistant (ART-R, kelch13-C580Y) and ART-sensitive (ART-S, kelch13-WT) parasites, recently isolated from Southeast Asian patients. Two striking results emerge: we observed (i) a strong genome-wide skew (>80%) towards alleles from the ART-R parent in the mosquito stage, that dropped to ~50% in the blood stage as selfed ART-R parasites were selected against; and (ii) repeatable allele specific skews in blood stage parasites with particularly strong selection (selection coefficient (s) ≤ 0.18/asexual cycle) against alleles from the ART-R parent at loci on chromosome 12 containing MRP2 and chromosome 14 containing ARPS10. This approach robustly identifies selected loci and has strong potential for identifying parasite genes that interact with the mosquito vector or compensatory loci involved in drug resistance.
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