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Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian Plasmodium falciparum populations.

Garg S, Alam MT, Das MK, Dev V, Kumar A, Dash AP, Sharma YD - Malar. J. (2007)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. sheenagarg2000@yahoo.com

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.

Conclusion: 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.

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Related in: MedlinePlus

Sliding window plot of the nucleotide diversity per site (π) comparing the level of genetic diversity among the domain I sequences of the parasite from all five study areas. The π values were calculated on DnaSP with window length 100 bp and step size of 25 bp. In all study areas, the maximum diversity was seen between the nucleotide positions 50 and 200 bps. n; number of P. falciparum isolates.
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Figure 1: Sliding window plot of the nucleotide diversity per site (π) comparing the level of genetic diversity among the domain I sequences of the parasite from all five study areas. The π values were calculated on DnaSP with window length 100 bp and step size of 25 bp. In all study areas, the maximum diversity was seen between the nucleotide positions 50 and 200 bps. n; number of P. falciparum isolates.

Mentions: The haplotype (gene) diversity (Hd) for all 157 sequences was calculated to be 0.948 ± 0.010 SD. The average number of pairwise nucleotide differences within Indian P. falciparum population (K) was 10.13 with the overall π diversity 0.0222 ± 0.0005 SD (Table 1). However, the sliding window analysis of the entire 456 bp region estimated π diversity ranging from 0.00668–0.05126 with the highest value between nucleotide positions 50 and 200 (0.01501 to 0.02488) (Figure 1). A total of 12 minimum number of recombination (Rm) events were observed between adjacent polymorphic sites (Table 2). The estimates of R = 4Nr between adjacent sites and per gene were 0.123 and 56.2 respectively. The haplotype diversity (Hd), nucleotide diversity per site (π) and average number of pairwise nucleotide differences within population (K) showed regional variations (Table 1). The π diversity was highest between nucleotide positions 50 and 200 among all five populations as estimated by sliding window method using a step size of 25 bp (Figure 1).


Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian Plasmodium falciparum populations.

Garg S, Alam MT, Das MK, Dev V, Kumar A, Dash AP, Sharma YD - Malar. J. (2007)

Sliding window plot of the nucleotide diversity per site (π) comparing the level of genetic diversity among the domain I sequences of the parasite from all five study areas. The π values were calculated on DnaSP with window length 100 bp and step size of 25 bp. In all study areas, the maximum diversity was seen between the nucleotide positions 50 and 200 bps. n; number of P. falciparum isolates.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2211494&req=5

Figure 1: Sliding window plot of the nucleotide diversity per site (π) comparing the level of genetic diversity among the domain I sequences of the parasite from all five study areas. The π values were calculated on DnaSP with window length 100 bp and step size of 25 bp. In all study areas, the maximum diversity was seen between the nucleotide positions 50 and 200 bps. n; number of P. falciparum isolates.
Mentions: The haplotype (gene) diversity (Hd) for all 157 sequences was calculated to be 0.948 ± 0.010 SD. The average number of pairwise nucleotide differences within Indian P. falciparum population (K) was 10.13 with the overall π diversity 0.0222 ± 0.0005 SD (Table 1). However, the sliding window analysis of the entire 456 bp region estimated π diversity ranging from 0.00668–0.05126 with the highest value between nucleotide positions 50 and 200 (0.01501 to 0.02488) (Figure 1). A total of 12 minimum number of recombination (Rm) events were observed between adjacent polymorphic sites (Table 2). The estimates of R = 4Nr between adjacent sites and per gene were 0.123 and 56.2 respectively. The haplotype diversity (Hd), nucleotide diversity per site (π) and average number of pairwise nucleotide differences within population (K) showed regional variations (Table 1). The π diversity was highest between nucleotide positions 50 and 200 among all five populations as estimated by sliding window method using a step size of 25 bp (Figure 1).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India. sheenagarg2000@yahoo.com

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus