First report of novel single-nucleotide polymorphisms and genetic characteristics in the open reading frame of the prion protein gene (PRNP) in bats

Background Prion diseases are fatal neurodegenerative disorders capable of causing transmissible spongiform encephalopathies (TSEs) and have been reported in humans and several animal species. Genetic polymorphisms in the prion protein gene ( PRNP ) are known to influence the conformational conversion of the normal cellular prion protein (PrP C ) into its pathogenic isoform (PrP Sc ), thereby affecting disease susceptibility and pathogenesis. However, single-nucleotide polymorphisms (SNPs) in the PRNP gene have not been reported in bats, which remain free from prion disease reports despite their wide ecological diversity. Methods We analyzed PRNP sequences from 94 bat samples and conducted comparative analyses with PRNP sequences from other animal species. The coding region of the bat PRNP gene was amplified and sequenced to identify genetic variants. Genotype, allele, and haplotype frequencies were calculated, and the potential functional and structural impacts of identified SNPs were predicted using in silico tools, including PolyPhen-2, PANTHER, SIFT, and SODA. Secondary and tertiary structures of bat PrP were modeled and visualized using SWISS-MODEL and Swiss-PdbViewer. Results Five polymorphisms were identified in the bat PRNP gene, among which only one non-synonymous SNP, c.86A>G (K29R), was detected. Linkage disequilibrium and haplotype analyses revealed moderate genetic diversity in the bat PRNP locus. In silico prediction indicated that the K29R substitution is likely to be functionally neutral, without notable alterations in protein solubility or secondary structure. The modeled PrP structure of bats showed high overall conservation compared with other mammalian species. Conclusion This study provides the first report describing PRNP genetic polymorphisms in bats, including the novel K29R variant. These findings offer essential insights into molecular evolution and possible mechanisms underlying natural resistance to prion diseases in bats.