Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian <it>Plasmodium falciparum </it>populations

<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>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 polymorphis...

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Main Authors: Kumar Ashwani, Dev Vas, Das Manoj K, Alam Mohammad T, Garg Sheena, Dash Aditya P, Sharma Yagya D
Format: Article
Language:English
Published: BMC 2007-11-01
Series:Malaria Journal
Online Access:http://www.malariajournal.com/content/6/1/154
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author Kumar Ashwani
Dev Vas
Das Manoj K
Alam Mohammad T
Garg Sheena
Dash Aditya P
Sharma Yagya D
author_facet Kumar Ashwani
Dev Vas
Das Manoj K
Alam Mohammad T
Garg Sheena
Dash Aditya P
Sharma Yagya D
author_sort Kumar Ashwani
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>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 <it>ama1 </it>gene among Indian <it>P. falciparum </it>isolates.</p> <p>Methods</p> <p>The part of the <it>ama</it>1 gene covering domain I was PCR amplified and sequenced from 157 <it>P. falciparum </it>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.</p> <p>Results</p> <p>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 π as compared to low malaria transmission areas (Uttar Pradesh and Goa). The comparison of all five Indian <it>P. falciparum </it>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.</p> <p>Conclusion</p> <p>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.</p>
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spelling doaj.art-8e5e2b03b1f64b788dbc205b8c9b52d82022-12-22T00:10:39ZengBMCMalaria Journal1475-28752007-11-016115410.1186/1475-2875-6-154Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian <it>Plasmodium falciparum </it>populationsKumar AshwaniDev VasDas Manoj KAlam Mohammad TGarg SheenaDash Aditya PSharma Yagya D<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>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 <it>ama1 </it>gene among Indian <it>P. falciparum </it>isolates.</p> <p>Methods</p> <p>The part of the <it>ama</it>1 gene covering domain I was PCR amplified and sequenced from 157 <it>P. falciparum </it>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.</p> <p>Results</p> <p>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 π as compared to low malaria transmission areas (Uttar Pradesh and Goa). The comparison of all five Indian <it>P. falciparum </it>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.</p> <p>Conclusion</p> <p>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.</p>http://www.malariajournal.com/content/6/1/154
spellingShingle Kumar Ashwani
Dev Vas
Das Manoj K
Alam Mohammad T
Garg Sheena
Dash Aditya P
Sharma Yagya D
Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian <it>Plasmodium falciparum </it>populations
Malaria Journal
title Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian <it>Plasmodium falciparum </it>populations
title_full Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian <it>Plasmodium falciparum </it>populations
title_fullStr Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian <it>Plasmodium falciparum </it>populations
title_full_unstemmed Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian <it>Plasmodium falciparum </it>populations
title_short Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian <it>Plasmodium falciparum </it>populations
title_sort sequence diversity and natural selection at domain i of the apical membrane antigen 1 among indian it plasmodium falciparum it populations
url http://www.malariajournal.com/content/6/1/154
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