Analysis of genetic diversity and population structure of gene encoding cell-traversal protein for ookinetes and sporozoites (CelTOS) vaccine candidate antigen in global Plasmodium falciparum populations

Analysis of genetic diversity and population structure of gene encoding cell-traversal protein... Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites (PfCelTOS) has been reported as one of the most attractive malaria vaccine candidate antigens. To design a broadly effective malaria vaccine based on this antigen, it is crucial to have adequate information on genetic diversity in global PfCelTOS. Therefore, the extent of sequence diversity at the full-length of the pfceltos was assessed among both natural P. falciparum isolates collected from Iran (n = 93) and from available global pfceltos sequence data retrieved from PlasmoDB database (n = 159). Also, recombination, natural selection, the degree of genetic differentiation as well as the predicted immunodominant regions in PfCelTOS were analyzed. In total, 40 SNPs (including 1 synonymous and 39 non-synonymous) were detected in 34 positions, as compared to 3D7 sequence, which led to 66 distinct haplotypes with different frequencies. Among those haplotypes, 34 (51.5%, excluded from further analysis) were singleton haplotype and mostly detected among Senegalese parasite isolates. PfCelt-1 was found as predominant haplotype (32.6% total frequency) that was only detected in Iranian P. falciparum isolates. Nucleotide diversity was low in French Guiana (0.00236 ± 0.00203) and Iranian (0.00259 ± 0.00048) P. falciparum isolates in comparison with African populations. Evidence for positive selection by host immunity and intragenic recombination were detected that are two key factors responsible for gene evolution and genetic diversity of pfceltos gene. The results of Fst analysis and haplotype network revealed that PfCelTOS antigen displayed evident genetic structure between geographical parasite populations. In conclusion, the present analysis demonstrates that there is a limited antigenic diversity and geographic variation in global PfCelTOS, and this finding may be associated with the critical function of this antigen in cell traversal of the parasite in sporozoite and ookinete. Besides, most of the predicted B- and T-cell epitopes were located in the conserved region of the gene, but most of the amino acid replacements were located at the C-terminal region of PfCelTOS. The obtained results in this investigation could provide knowledge for better design of PfCelTOS-based malaria vaccine. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Infection, Genetics and Evolution Elsevier

Analysis of genetic diversity and population structure of gene encoding cell-traversal protein for ookinetes and sporozoites (CelTOS) vaccine candidate antigen in global Plasmodium falciparum populations

Loading next page...
 
/lp/elsevier/analysis-of-genetic-diversity-and-population-structure-of-gene-2xB88oSp0p
Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier Ltd
ISSN
1567-1348
D.O.I.
10.1016/j.meegid.2018.01.023
Publisher site
See Article on Publisher Site

Abstract

Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites (PfCelTOS) has been reported as one of the most attractive malaria vaccine candidate antigens. To design a broadly effective malaria vaccine based on this antigen, it is crucial to have adequate information on genetic diversity in global PfCelTOS. Therefore, the extent of sequence diversity at the full-length of the pfceltos was assessed among both natural P. falciparum isolates collected from Iran (n = 93) and from available global pfceltos sequence data retrieved from PlasmoDB database (n = 159). Also, recombination, natural selection, the degree of genetic differentiation as well as the predicted immunodominant regions in PfCelTOS were analyzed. In total, 40 SNPs (including 1 synonymous and 39 non-synonymous) were detected in 34 positions, as compared to 3D7 sequence, which led to 66 distinct haplotypes with different frequencies. Among those haplotypes, 34 (51.5%, excluded from further analysis) were singleton haplotype and mostly detected among Senegalese parasite isolates. PfCelt-1 was found as predominant haplotype (32.6% total frequency) that was only detected in Iranian P. falciparum isolates. Nucleotide diversity was low in French Guiana (0.00236 ± 0.00203) and Iranian (0.00259 ± 0.00048) P. falciparum isolates in comparison with African populations. Evidence for positive selection by host immunity and intragenic recombination were detected that are two key factors responsible for gene evolution and genetic diversity of pfceltos gene. The results of Fst analysis and haplotype network revealed that PfCelTOS antigen displayed evident genetic structure between geographical parasite populations. In conclusion, the present analysis demonstrates that there is a limited antigenic diversity and geographic variation in global PfCelTOS, and this finding may be associated with the critical function of this antigen in cell traversal of the parasite in sporozoite and ookinete. Besides, most of the predicted B- and T-cell epitopes were located in the conserved region of the gene, but most of the amino acid replacements were located at the C-terminal region of PfCelTOS. The obtained results in this investigation could provide knowledge for better design of PfCelTOS-based malaria vaccine.

Journal

Infection, Genetics and EvolutionElsevier

Published: Apr 1, 2018

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

Monthly Plan

  • Read unlimited articles
  • Personalized recommendations
  • No expiration
  • Print 20 pages per month
  • 20% off on PDF purchases
  • Organize your research
  • Get updates on your journals and topic searches

$49/month

Start Free Trial

14-day Free Trial

Best Deal — 39% off

Annual Plan

  • All the features of the Professional Plan, but for 39% off!
  • Billed annually
  • No expiration
  • For the normal price of 10 articles elsewhere, you get one full year of unlimited access to articles.

$588

$360/year

billed annually
Start Free Trial

14-day Free Trial