Sarcocystis neurona major surface antigen gene 1 (SAG1) shows evidence of having evolved under positive selection pressure

Abstract

The major surface antigen gene 1 (SAG1) is conserved among members of Sarcocystidae and may play an important role in parasite pathogenesis. Additionally, generation and selection of different antigenic variants of SAG1 has the potential for inclusion in a subunit vaccine or in the development of a diagnostic assay. In this study, patterns of nucleotide polymorphism were used to test the hypothesis that natural selection promotes diversity in different parts of SAG1 of Sarcocystis neurona. Nucleotide and amino acid sequence analysis of SAG1 from multiple S. neurona isolates identified two alleles. Sequences were identical intra-allele and highly divergent inter-alleles. Also, phylogenetic reconstruction showed sequences clustering into two clades. Tajima's and Fu and Li's neutrality tests indicated that selection is more likely to be acting on SAG1. Moreover, a sliding window analysis based on the ratio of silent substitutions to amino acid replacements provided strong evidence that two short segments in the central and 3' domain of SAG1 have been under positive selection in the divergence of the two alleles, suggesting that it may be important for the evasion of host immune responses and would be a suitable target for vaccine development.