| Mutation Description |
"Finally, the data for the nine-banded armadillo, one of the three Cingulata species analysed, is ambiguous. The PCSK9 sequence displays multiple features suggesting that the gene is functional—conservation of a 12-exon structure, conserved internal exon sizes, absence of nonsense mutations, and conservation of known functionally important amino acids (SF1)—but the genomic reference sequence has a 1-bp deletion in exon 12, which should result in a nonfunctional protein. In the reference sequence, this alteration has been “compensated for” by a 3′ extension of exon 11 to include an additional 10 bp (SF2). As this entails the use on a non-canonical splice donor sequence, it is unlikely that it reflects the true transcript. A third possibility is that the 1-bp deletion is not actually present in the DNA of theninebanded armadillo. Indeed, the genome of the species was sequenced at low coverage (6×), and the only available raw sequence covering the intron 11-exon 12 border does not have the 1-bp deletion in exon 12—although a single raw sequence is insufficient to settle this issue. An additional unusual feature of PCSK9 in the nine-banded armadillo is that the stop codon is positioned 114 bp downstream relative to its human counterpart. However, it is also unlikely that this has an impact on protein function, since even larger C-terminal tags have been engineered into human PCSK9 without apparent functional impairment (Poirier et al. 2016)." |
10.1007/s10709-021-00113-x |