title: Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia.
abstract: Cambodia, in which both Plasmodium vivax and Plasmodium falciparum are endemic, has been the focus of numerous malaria-control interventions, resulting in a marked decline in overall malaria incidence. Despite this decline, the number of P vivax cases has actually increased. To understand better the factors underlying this resilience, we compared the genetic responses of the two species to recent selective pressures. We sequenced and studied the genomes of 70 P vivax and 80 P falciparum isolates collected between 2009 and 2013. We found that although P falciparum has undergone population fracturing, the coendemic P vivax population has grown undisrupted, resulting in a larger effective population size, no discernable population structure, and frequent multiclonal infections. Signatures of selection suggest recent, species-specific evolutionary differences. Particularly, in contrast to P falciparum, P vivax transcription factors, chromatin modifiers, and histone deacetylases have undergone strong directional selection, including a particularly strong selective sweep at an AP2 transcription factor. Together, our findings point to different population-level adaptive mechanisms used by P vivax and P falciparum parasites. Although population substructuring in P falciparum has resulted in clonal outgrowths of resistant parasites, P vivax may use a nuanced transcriptional regulatory approach to population maintenance, enabling it to preserve a larger, more diverse population better suited to facing selective threats. We conclude that transcriptional control may underlie P vivax's resilience to malaria control measures. Novel strategies to target such processes are likely required to eradicate P vivax and achieve malaria elimination.
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Parobek
authors.affiliation: Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Jessica T
authors.initials: JT
authors.lastname: Lin
authors.affiliation: US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand 10400.
authors.forename: David L
authors.initials: DL
authors.lastname: Saunders
authors.affiliation: Upstate Medical University, State University of New York, Syracuse, NY 13210.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Barnett
authors.affiliation: US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand 10400.|US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Phnom Penh, Cambodia.
authors.forename: Chanthap
authors.initials: C
authors.lastname: Lon
authors.affiliation: US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand 10400.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Lanteri
authors.affiliation: Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Sujata
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Brazeau
authors.affiliation: Program in Bioinformatics and Integrative Biology, University of Massachusetts School of Medicine, Worcester, MA 01655.
authors.forename: Derrick K
authors.initials: DK
authors.lastname: DeConti
authors.affiliation: Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Deen L
authors.initials: DL
authors.lastname: Garba
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Meshnick
authors.affiliation: US Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand 10400.
authors.forename: Michele D
authors.initials: MD
authors.lastname: Spring
authors.affiliation: National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia.
authors.forename: Char Meng
authors.initials: CM
authors.lastname: Chuor
authors.affiliation: Program in Bioinformatics and Integrative Biology, University of Massachusetts School of Medicine, Worcester, MA 01655.|Division of Transfusion Medicine, University of Massachusetts School of Medicine, Worcester, MA 01655.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bailey
authors.affiliation: Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; jjuliano@med.unc.edu.|Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.|Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Juliano
mesh_terms: D002160:Cambodia / Q000453:epidemiology; D056915:DNA Copy Number Variations; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D019353:Endemic Diseases / Q000517:prevention & control; D014644:Genetic Variation; D018503:Genome, Protozoan; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology / Q000517:prevention & control; D016780:Malaria, Vivax / Q000453:epidemiology / Q000469:parasitology* / Q000517:prevention & control*; D010963:Plasmodium falciparum / Q000235:genetics; D010966:Plasmodium vivax / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D013045:Species Specificity; D014158:Transcription, Genetic
chemical_list: D016054:DNA, Protozoan
keywords: Plasmodium; genome; malaria; transcription; vivax