title: Genomic analysis of local variation and recent evolution in Plasmodium vivax.
abstract: The widespread distribution and relapsing nature of Plasmodium vivax infection present major challenges for the elimination of malaria. To characterize the genetic diversity of this parasite in individual infections and across the population, we performed deep genome sequencing of >200 clinical samples collected across the Asia-Pacific region and analyzed data on >300,000 SNPs and nine regions of the genome with large copy number variations. Individual infections showed complex patterns of genetic structure, with variation not only in the number of dominant clones but also in their level of relatedness and inbreeding. At the population level, we observed strong signals of recent evolutionary selection both in known drug resistance genes and at new loci, and these varied markedly between geographical locations. These findings demonstrate a dynamic landscape of local evolutionary adaptation in the parasite population and provide a foundation for genomic surveillance to guide effective strategies for control and elimination of P. vivax.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.|MRC Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Pearson
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.|MRC Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.
authors.forename: Roberto
authors.initials: R
authors.lastname: Amato
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territories 0811, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Auburn
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.|MRC Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.|Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Olivo
authors.initials: O
authors.lastname: Miotto
authors.affiliation: MRC Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.
authors.forename: Jacob
authors.initials: J
authors.lastname: Almagro-Garcia
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
authors.forename: Chanaki
authors.initials: C
authors.lastname: Amaratunga
authors.affiliation: National Centre for Parasitology, Entomology, and Malaria Control, Phnom Penh, Cambodia.
authors.forename: Seila
authors.initials: S
authors.lastname: Suon
authors.affiliation: Sampov Meas Referral Hospital, Pursat, Cambodia.
authors.forename: Sivanna
authors.initials: S
authors.lastname: Mao
authors.affiliation: Eijkman Institute for Molecular Biology, Jakarta 10430, Indonesia.
authors.forename: Rintis
authors.initials: R
authors.lastname: Noviyanti
authors.affiliation: Eijkman Institute for Molecular Biology, Jakarta 10430, Indonesia.
authors.forename: Hidayat
authors.initials: H
authors.lastname: Trimarsanto
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territories 0811, Australia.
authors.forename: Jutta
authors.initials: J
authors.lastname: Marfurt
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territories 0811, Australia.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
authors.affiliation: Infectious Diseases Society Sabah-Menzies School of Health Research Clinical Research Unit and Queen Elizabeth Hospital Clinical Research Centre, Kota Kinabalu, Sabah, Malaysia.
authors.forename: Timothy
authors.initials: T
authors.lastname: William
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Maciej F
authors.initials: MF
authors.lastname: Boni
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Christiane
authors.initials: C
authors.lastname: Dolecek
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Tinh Tran
authors.initials: TT
authors.lastname: Hien
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.|Faculty of Medicine and Health Sciences, Divine Word University, Madang, Papua New Guinea.
authors.forename: Pascal
authors.initials: P
authors.lastname: Michon
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Peter
authors.initials: P
authors.lastname: Siba
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Livingstone
authors.initials: L
authors.lastname: Tavul
authors.affiliation: Division of Population Health and Immunity, The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Harrison
authors.affiliation: Division of Population Health and Immunity, The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Barry
authors.affiliation: Division of Population Health and Immunity, The Walter and Eliza Hall Institute for Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Marcelo U
authors.initials: MU
authors.lastname: Ferreira
authors.affiliation: Department of Parasitology, Faculty of Medicine, University of Colombo, Sri Lanka.
authors.forename: Nadira
authors.initials: N
authors.lastname: Karunaweera
authors.affiliation: Institut Pasteur de Madagascar, Antananarivo, Madagascar.
authors.forename: Milijaona
authors.initials: M
authors.lastname: Randrianarivelojosia
authors.affiliation: Jiangsu Institute of Parasitic Diseases, Key Laboratory of Parasitic Disease Control and Prevention (Ministry of Health), Jiangsu Provincial Key Laboratory of Parasite Molecular Biology, Wuxi, Jiangsu, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Gao
authors.affiliation: MRC Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.
authors.forename: Christina
authors.initials: C
authors.lastname: Hubbart
authors.affiliation: MRC Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.
authors.forename: Lee
authors.initials: L
authors.lastname: Hart
authors.affiliation: MRC Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Jeffery
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Drury
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Mead
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Mihir
authors.initials: M
authors.lastname: Kekre
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Susana
authors.initials: S
authors.lastname: Campino
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Magnus
authors.initials: M
authors.lastname: Manske
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.|MRC Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Cornelius
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Bronwyn
authors.initials: B
authors.lastname: MacInnis
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.|MRC Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Rockett
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.|MRC Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.
authors.forename: Alistair
authors.initials: A
authors.lastname: Miles
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rayner
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Fairhurst
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok 10400, Thailand.|Shoklo Malaria Research Unit, Mae Sot, Tak 63110, Thailand.
authors.forename: Francois
authors.initials: F
authors.lastname: Nosten
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territories 0811, Australia.|Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, OX3 7LJ, UK.
authors.forename: Ric N
authors.initials: RN
authors.lastname: Price
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.|MRC Centre for Genomics and Global Health, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, UK.
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Kwiatkowski
mesh_terms: D005075:Biological Evolution; D005819:Genetic Markers / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D023281:Genomics / Q000379:methods*; D006801:Humans; D016780:Malaria, Vivax / Q000235:genetics* / Q000469:parasitology / Q000635:transmission; D010966:Plasmodium vivax / Q000235:genetics* / Q000472:pathogenicity
chemical_list: D005819:Genetic Markers