title: Worldwide population genetic analysis and natural selection in the Plasmodium vivax Generative Cell Specific 1 (PvGCS1) as a transmission-blocking vaccine candidate.
abstract: GENERATIVE CELL SPECIFIC 1 (GCS1) is one of the Transmission Blocking Vaccine (TBV) candidate antigens, which is expressed on the surface of male gametocytes and gametes of Plasmodium species. Since antigenic diversity could inhibit the successful development of a malaria vaccine, it is crucial to determine the diversity of gcs1 gene in global malaria-endemic areas. Therefore, gene diversity and selection of gcs1 gene were analyzed in Iranian Plasmodium vivax isolates (n=52) and compared with the corresponding sequences from worldwide clinical P. vivax isolates available in PlasmoDB database. Totally 12 SNPs were detected in the pvgcs1 sequences as compared to Sal-1 sequence. Five out of 12 SNPs including three synonymous (T797C, G1559A, and G1667T) and two amino acid replacements (Y133S and Q634P) were detected in Iranian pvgcs1 sequences. According to four amino acid replacements (Y133S, N575S, Q634P and D637N) observed in all world PvGCS1 sequences, totally 5 PvGCS1 haplotypes were detected in the world, that three of them observed in Iranian isolates including the PvGCS-A (133S/634Q, 92.3%), PvGCS-B (133Y/634Q, 5.8%), and PvGCS-C (133S/634P, 1.9%). The overall nucleotide diversity (π) for all 52 sequences of Iranian pvgcs1 gene was 0.00018±0.00006, and the value of dN-dS (-0.00031) were negative, however, it was not statistically significant. In comparison with global isolates, Iranian and PNG pvgcs1 sequences had the lowest nucleotide and haplotype diversity, while the highest nucleotide and haplotype diversity was observed in China population. Moreover, epitope prediction in this antigen showed that all B-cell epitopes were located in conserved regions. However, Q634P (in one Iranian isolate) and D637N (observed in Thailand, China, Vietnam and North Korea) mutations are involved in predicted IURs. The obtained results in this study could be used in development of PvGCS1 based malaria vaccine.
authors.affiliation: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, P.O. Box 1316943551, Tehran, Iran. Electronic address: abouei@gmail.com.
authors.forename: Akram Abouie
authors.initials: AA
authors.lastname: Mehrizi
authors.affiliation: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, P.O. Box 1316943551, Tehran, Iran; Department of Genetics, Tehran Medical Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Dodangeh
authors.affiliation: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, P.O. Box 1316943551, Tehran, Iran.
authors.forename: Sedigheh
authors.initials: S
authors.lastname: Zakeri
authors.affiliation: Malaria and Vector Research Group (MVRG), Biotechnology Research Center (BRC), Pasteur Institute of Iran, P.O. Box 1316943551, Tehran, Iran.
authors.forename: Navid Dinparast
authors.initials: ND
authors.lastname: Djadid
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000953:Antigens, Protozoan; D002648:Child; D005260:Female; D014644:Genetic Variation; D005828:Genetics, Population; D006801:Humans; D007492:Iran; D017780:Malaria Vaccines; D016780:Malaria, Vivax / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010966:Plasmodium vivax / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines
keywords: Generative cell specific 1 (GCS1); Genetic diversity; Plasmodium vivax