TY - JOUR
T1 - Plasmodium vivax
T2 - Sequence polymorphism and effect of natural selection at apical membrane antigen 1 (PvAMA1) among Indian population
AU - Thakur, Ankur
AU - Alam, Mohammad Tauqeer
AU - Bora, Hema
AU - Kaur, Punit
AU - Sharma, Yagya D.
N1 - Funding Information:
We thank Dr. Sumiti Vinayak for help in analyzing the data and proofreading the manuscript. We also thank Manoj Kumar for his help in generating the 3-D structure of PvAMA1. MTA (for Senior Research Fellowship) and HB (for Junior Research Fellowship) acknowledge Council of Scientific and Industrial Research (CSIR) and Indian Council of Medical Research (ICMR), respectively. Financial support for the work granted by Indian Council of Medical Research (ICMR), and Department of Biotechnology (DBT), Government of India, is acknowledged. We are also grateful to Bioinformatics facilities of Biotechnology Information System (BTIS).
PY - 2008/8/1
Y1 - 2008/8/1
N2 - Present study describes the characterization of apical membrane antigen 1 (PvAMA1) polymorphisms among Indian Plasmodium vivax isolates. The partial PvAMA1 gene (covering domain I and domain II regions) sequenced from sixty-one (n = 61) isolates in this study resulted into 49 haplotypes. Comparison with the previously available PvAMA1 sequences in the GenBank database revealed that 45 of these were new haplotypes that have never been reported till date. For further analyses, we also included 11 previously reported PvAMA1 sequences from India available in the database. Thus genetic diversity and effect of natural selection were analyzed both at domain I and domain II of this promising malaria vaccine candidate among 72 Indian P. vivax isolates. Non-synonymous mutations were found at 25 codons (16 at domain I and 9 at domain II) where 17 codons were dimorphic while rest of them (8 codons) were trimorphic. Thus codon polymorphisms were observed to be more at domain I as compared to domain II. Although the difference between the rate of non-synonymous (dN) and synonymous (dS) mutations was positive (dN-dS, 0.002 ± 0.004SE) at domain II, it was not significantly different from each other (P = 0.272), indicating tendency of stronger diversifying selection at this domain. The dN-dS difference for domain I (- 0.006 ± 0.009SE, P = 0.268) and for entire 900 bp region (- 0.002 ± 0.005E, P = 0.320) being negative and statistically insignificant suggests the role of both positive as well as purifying selection. Three-dimensional distributions of all polymorphic residues were mapped on a modeled PvAMA1 structure. Results suggested that almost all of the observed polymorphisms were located at one surface of the antigen. In conclusion, PvAMA1 antigen displays high diversity among Indian isolates with more diversifying selection at domain II. The result has significant value in malaria vaccine development using this antigen.
AB - Present study describes the characterization of apical membrane antigen 1 (PvAMA1) polymorphisms among Indian Plasmodium vivax isolates. The partial PvAMA1 gene (covering domain I and domain II regions) sequenced from sixty-one (n = 61) isolates in this study resulted into 49 haplotypes. Comparison with the previously available PvAMA1 sequences in the GenBank database revealed that 45 of these were new haplotypes that have never been reported till date. For further analyses, we also included 11 previously reported PvAMA1 sequences from India available in the database. Thus genetic diversity and effect of natural selection were analyzed both at domain I and domain II of this promising malaria vaccine candidate among 72 Indian P. vivax isolates. Non-synonymous mutations were found at 25 codons (16 at domain I and 9 at domain II) where 17 codons were dimorphic while rest of them (8 codons) were trimorphic. Thus codon polymorphisms were observed to be more at domain I as compared to domain II. Although the difference between the rate of non-synonymous (dN) and synonymous (dS) mutations was positive (dN-dS, 0.002 ± 0.004SE) at domain II, it was not significantly different from each other (P = 0.272), indicating tendency of stronger diversifying selection at this domain. The dN-dS difference for domain I (- 0.006 ± 0.009SE, P = 0.268) and for entire 900 bp region (- 0.002 ± 0.005E, P = 0.320) being negative and statistically insignificant suggests the role of both positive as well as purifying selection. Three-dimensional distributions of all polymorphic residues were mapped on a modeled PvAMA1 structure. Results suggested that almost all of the observed polymorphisms were located at one surface of the antigen. In conclusion, PvAMA1 antigen displays high diversity among Indian isolates with more diversifying selection at domain II. The result has significant value in malaria vaccine development using this antigen.
KW - DNA sequencing
KW - Diversifying selection
KW - Genetic diversity
KW - Malaria antigen
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U2 - 10.1016/j.gene.2008.04.012
DO - 10.1016/j.gene.2008.04.012
M3 - Article
C2 - 18547744
AN - SCOPUS:45449086019
SN - 0378-1119
VL - 419
SP - 35
EP - 42
JO - Gene
JF - Gene
IS - 1-2
ER -