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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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The linkage disequilibrium (LD) plot showing non-random association between nucleotide variants at different polymorphic sites. The R^2 values are plotted against the nucleotide distances with two-tailed Fisher's exact test of significance using DnaSP. The value of LD index (range from -1 to +1) declines with increasing nucleotide distance, indicating that recombination events are taking place. The analysis was performed considering all polymorphic sites. (A) Assam, (B) Orissa, (C) A & N, (D) Goa, (E) UP, and (F) Total.
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Figure 3: The linkage disequilibrium (LD) plot showing non-random association between nucleotide variants at different polymorphic sites. The R^2 values are plotted against the nucleotide distances with two-tailed Fisher's exact test of significance using DnaSP. The value of LD index (range from -1 to +1) declines with increasing nucleotide distance, indicating that recombination events are taking place. The analysis was performed considering all polymorphic sites. (A) Assam, (B) Orissa, (C) A & N, (D) Goa, (E) UP, and (F) Total.

Mentions: The minimum number of recombination events (Rm) between adjacent polymorphic sites for Assam, Orissa, A & N, UP and Goa isolates were 9, 11, 7, 8 and 6 respectively (Table 2). The value of R (both between adjacent sites and for the entire domain) was highest in Assam (0.178 and 81), followed by Orissa (0.118 and 53.7), Goa (0.0741 and 33.3), A & N (0.0571 and 26), and UP (0.0165 and 8) parasite population. The higher value of the recombination parameters (Rm and R) indicate that high meiotic recombination is taking place between the sites generating genetic diversity in the gene. As LD index R^2 plotted against the nucleotide distances also demonstrated a decline across the entire 456 bp region (Figure 3), it can be assumed that intragenic recombination may be contributing to the increased diversity observed at AMA1 domain I.


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)

The linkage disequilibrium (LD) plot showing non-random association between nucleotide variants at different polymorphic sites. The R^2 values are plotted against the nucleotide distances with two-tailed Fisher's exact test of significance using DnaSP. The value of LD index (range from -1 to +1) declines with increasing nucleotide distance, indicating that recombination events are taking place. The analysis was performed considering all polymorphic sites. (A) Assam, (B) Orissa, (C) A & N, (D) Goa, (E) UP, and (F) Total.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: The linkage disequilibrium (LD) plot showing non-random association between nucleotide variants at different polymorphic sites. The R^2 values are plotted against the nucleotide distances with two-tailed Fisher's exact test of significance using DnaSP. The value of LD index (range from -1 to +1) declines with increasing nucleotide distance, indicating that recombination events are taking place. The analysis was performed considering all polymorphic sites. (A) Assam, (B) Orissa, (C) A & N, (D) Goa, (E) UP, and (F) Total.
Mentions: The minimum number of recombination events (Rm) between adjacent polymorphic sites for Assam, Orissa, A & N, UP and Goa isolates were 9, 11, 7, 8 and 6 respectively (Table 2). The value of R (both between adjacent sites and for the entire domain) was highest in Assam (0.178 and 81), followed by Orissa (0.118 and 53.7), Goa (0.0741 and 33.3), A & N (0.0571 and 26), and UP (0.0165 and 8) parasite population. The higher value of the recombination parameters (Rm and R) indicate that high meiotic recombination is taking place between the sites generating genetic diversity in the gene. As LD index R^2 plotted against the nucleotide distances also demonstrated a decline across the entire 456 bp region (Figure 3), it can be assumed that intragenic recombination may be contributing to the increased diversity observed at AMA1 domain I.

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