title: Selections, frameshift mutations, and copy number variation detected on the surf4.1gene in the western Kenyan Plasmodium falciparum population.
abstract: Plasmodium falciparum SURFIN4.1is a putative ligand expressed on the merozoite and likely on the infected red blood cell, whose gene was suggested to be under directional selection in the eastern Kenyan population, but under balancing selection in the Thai population. To understand this difference, surf4.1sequences of western Kenyan P. falciparum isolates were analysed. Frameshift mutations and copy number variation (CNV) were also examined for the parasites from western Kenya and Thailand.
  
  
  
  Positively significant departures from neutral expectations were detected on the surf4.1region encoding C-terminus of the variable region 2 (Var2) by 3 population-based tests in the western Kenyan population as similar in the Thai population, which was not covered by the previous analysis for eastern Kenyan population. Significant excess of non-synonymous substitutions per nonsynonymous site over synonymous substitutions per synonymous site was also detected in the Var2 region. Negatively significant departures from neutral expectations was detected on the region encoding Var1 C-terminus consistent to the previous observation in the eastern Kenyan population. Parasites possessing a frameshift mutation resulting a product without intracellular Trp-rich (WR) domains were 22/23 in western Kenya and 22/36 in Thailand. More than one copy of surf4.1gene was detected in western Kenya (4/24), but no CNV was found in Thailand (0/36).
  
  
  
  The authors infer that the high polymorphism of SURFIN4.1Var2 C-terminus in both Kenyan and Thai populations were shaped-up by diversifying selection and maintained by balancing selection. These phenomena were most likely driven by immunological pressure. Whereas the SURFIN4.1Var1 C-terminus is suggested to be under directional selection consistent to the previous report for the eastern Kenyan population. Most western Kenyan isolates possess a frameshift mutation that would limit the expression of SURFIN4.1on the merozoite, but only 60% of Thai isolates possess this frameshift, which would affect the level and type of the selection pressure against this protein as seen in the two extremities of Tajima's D values for Var1 C-terminus between Kenyan and Thai populations. CNV observed in Kenyan isolates may be a consequence of this frameshift mutation to increase benefits on the merozoite surface.
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.|Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.|Department of Clinical Medicine, Mount Kenya University, PO Box 342-01000, Thika, Kenya.
authors.forename: Jesse N
authors.initials: JN
authors.lastname: Gitaka
authors.affiliation: Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Radioisotope Centre, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Island Malaria Group, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Nobels väg 16, SE 171 77, Stockholm, Sweden.|Department of Parasitology and Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, 56000, Kuala Lumpur, Malaysia.
authors.forename: Zulkarnain Md
authors.initials: ZM
authors.lastname: Idris
authors.affiliation: Island Malaria Group, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Nobels väg 16, SE 171 77, Stockholm, Sweden.
authors.forename: Chim W
authors.initials: CW
authors.lastname: Chan
authors.affiliation: Nairobi Research Station, Nagasaki University Institute of Tropical Medicine-Kenya Medical Research Institute (NUITM-KEMRI) Project, Institute of Tropical Medicine (NEKKEN), Nagasaki University, P. O. Box 19993-00202, Nairobi, Kenya.
authors.forename: James
authors.initials: J
authors.lastname: Kongere
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.|Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yahata
authors.affiliation: Department of Clinical Medicine, Mount Kenya University, PO Box 342-01000, Thika, Kenya.
authors.forename: Francis W
authors.initials: FW
authors.lastname: Muregi
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.|Nairobi Research Station, Nagasaki University Institute of Tropical Medicine-Kenya Medical Research Institute (NUITM-KEMRI) Project, Institute of Tropical Medicine (NEKKEN), Nagasaki University, P. O. Box 19993-00202, Nairobi, Kenya.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ichinose
authors.affiliation: Island Malaria Group, Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Nobels väg 16, SE 171 77, Stockholm, Sweden.|Department of Parasitology and Research Center for Infectious Disease Sciences, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.|Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kaneko
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan. okaneko@nagasaki-u.ac.jp.|Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan. okaneko@nagasaki-u.ac.jp.
authors.forename: Osamu
authors.identifier: 0000-0003-0675-8296
authors.initials: O
authors.lastname: Kaneko
mesh_terms: D016368:Frameshift Mutation; D018628:Gene Dosage; D007630:Kenya; D008565:Membrane Proteins / Q000235:genetics*; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013785:Thailand
chemical_list: D008565:Membrane Proteins; D015800:Protozoan Proteins; C583416:SURFIN4.1 protein, Plasmodium falciparum
keywords: Copy number variation; Frameshift; Malaria; Plasmodium falciparum; SURFIN4.1; Selection