Novel polymorphisms and functional characterization of the prion protein gene in sparrows ().

Abstract

BACKGROUND: Misfolding of the prion protein (PrP) into an aberrant conformation causes prion diseases in several mammalian species; however, no prion infections have been documented in birds so far. The prion protein gene () has been extensively studied in mammals, but little is known aboutpolymorphisms in avian species and their potential roles in resistance to prion pathogenesis. However, the genetic variation of the sparrowgene remains largely uncharacterized. MATERIALS AND METHODS: To better understand the genetic diversity ofgene in sparrows, we sequenced the coding region from genomic DNA of 44 individuals. We analyzed the genetic characteristics of the sparrowgene, including genotype, allele, and haplotype distributions, as well as linkage disequilibrium (LD) among single nucleotide polymorphisms (SNPs) and insertion/deletion (indel) variants. The functional effects of the identified polymorphisms were predicted using multipletools, including PolyPhen-2, SIFT, AMYCO, SODA, and MutPred-Indel. In addition, the structural impact of non-synonymous substitutions was assessed by structural modeling tools, and the amino acid sequences of the hexapeptide tandem repeat were compared across avian species. RESULTS: A total of 24 polymorphisms were identified in the sparrowgene, including 9 non-synonymous substitutions and 3 indels. Among these, the A121V substitution was predicted to have the most detrimental effect, causing pronounced structural perturbation and increased amyloid propensity of sparrow PrP. The L5P and W105R substitutions also showed potentially deleterious impacts on protein stability. Among the indel polymorphisms, c.190_207delAACCCGGGCTACCCCCAC and c.243_244insAACCCCGGCTACCCCCAC were predicted to reduce solubility, whereas c.225_226insAACCCGGGCTACCCCCAC increased solubility. Furthermore, sparrow PrP exhibited a comparable length to that of quail, with both species containing eight hexapeptide repeat units. CONCLUSION: As far as we know, this study represents the first report of PRNP genetic polymorphisms in sparrows, providing baseline data for future studies on avian prion resistance.