Genetic diversity and effect of natural selection at apical membrane antigen-1 (AMA-1) among Iranian XXXX isolates.

@entity71393 @entity71392 @entity71396 @entity71397 @entity71391 @entity535 @entity71399 @entity70985 @entity71388 @entity3965 @entity71401 @entity71394 @entity71395 @entity71398 @entity311 @entity71400 @entity71389 @entity71390
Apical membrane antigen-1 (AMA-1) of @entity3965 Grassi et Feletti, 1890 is a promising @entity311 vaccine candidate. However, antigenic variation is a major problem to design a universal @entity311 vaccine. Hence, detailed understanding of the pvama-1 gene polymorphism can provide conductive information on this potential vaccine component. Therefore, this study investigated the extent of genetic polymorphisms at domain I (DI), DII and partial DIII of AMA-1 among Iranian @entity3965 isolates. Out of 107 blood samples, 92 were analysed based on the quality of the sequencing data. The sequences were classified into 53 haplotypes. @entity535 changes were observed at 31 positions that 17 were located at DI, 11 were at DII and the rest of them (3 positions) were at DIII. Thus, codon polymorphisms at DI were found to be higher than DII. Also, five of these polymorphic codons ( @entity71388 , @entity71389 , @entity71390 , @entity71391 , @entity71392 ) were novel and have not been reported yet. Neutrality analysis by using the dN-dS difference (the difference between the rate of non-synonymous and synonymous mutations) showed a negative diversifying selection at DI, DII and across the length of both domains. The potential B-cell epitopes were found in 5 regions of the PvAMA-1 with 10 mutation sites ( @entity71393 , @entity71394 , @entity71395 /K/D, @entity71396 /E, @entity71397 , @entity71398 , @entity71388 , @entity71399 , @entity71400 , @entity70985 ), whereas only one mutation ( @entity71401 ) has been detected in intrinsically unstructured/disordered regions. Fixation index (Fst) estimation between Iranian and Indian isolates (0.0131) indicated a significant low genetic differentiation. Distribution of the polymorphic sites and IURs mapped on a three dimensional structure of PvAMA-1 showed that these regions were located at two opposite faces of the molecule. In conclusion, the results have significant value in the design and development of a @entity311 vaccine based on this antigen.
