title: Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian Plasmodium falciparum populations.
abstract: BACKGROUND
  The Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading malaria vaccine candidate antigen. The complete AMA1 protein is comprised of three domains where domain I exhibits high sequence polymorphism and is thus named as the hyper-variable region (HVR). The present study describes the extent of genetic polymorphism and natural selection at domain I of the ama1 gene among Indian P. falciparum isolates.
  
  
  METHODS
  The part of the ama1 gene covering domain I was PCR amplified and sequenced from 157 P. falciparum isolates collected from five different geographical regions of India. Statistical and phylogenetic analyses of the sequences were done using DnaSP ver. 4. 10. 9 and MEGA version 3.0 packages.
  
  
  RESULTS
  A total of 57 AMA1 haplotypes were observed among 157 isolates sequenced. Forty-six of these 57 haplotypes are being reported here for the first time. The parasites collected from the high malaria transmission areas (Assam, Orissa, and Andaman and Nicobar Islands) showed more haplotypes (H) and nucleotide diversity pi as compared to low malaria transmission areas (Uttar Pradesh and Goa). The comparison of all five Indian P. falciparum subpopulations indicated moderate level of genetic differentiation and limited gene flow (Fixation index ranging from 0.048 to 0.13) between populations. The difference between rates of non-synonymous and synonymous mutations, Tajima's D and McDonald-Kreitman test statistics suggested that the diversity at domain I of the AMA1 antigen is due to positive natural selection. The minimum recombination events were also high indicating the possible role of recombination in generating AMA1 allelic diversity.
  
  
  CONCLUSIONS
  The level of genetic diversity and diversifying selection were higher in Assam, Orissa, and Andaman and Nicobar Islands populations as compared to Uttar Pradesh and Goa. The amounts of gene flow among these populations were moderate. The data reported here will be valuable for the development of AMA1-based malaria vaccine.
authors.affiliation: Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. sheenagarg2000@yahoo.com
authors.forename: Sheena
authors.initials: S
authors.lastname: Garg
authors.forename: Mohammad T
authors.initials: MT
authors.lastname: Alam
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Das
authors.forename: Vas
authors.initials: V
authors.lastname: Dev
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.forename: Aditya P
authors.initials: AP
authors.lastname: Dash
authors.forename: Yagya D
authors.initials: YD
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D017780:Malaria Vaccines / Q000276:immunology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000469:parasitology; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D044469:Racial Groups; D012641:Selection, Genetic
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium