Fig 1.
Illustration of PCSKS domains and the amino acids which codon has been under positive selection during placental mammalian evolution. Domains are in different colors as indicated.
Fig 2.
The comparative genomic regions surrounding the PCSK9 gene or remnants in the genome of the species with intact or putatively lost PCSK9.
The red vertical lines indicate the genomic location of the PCSK9 remnants.
Fig 3.
The comparative genomic region around PCSK9 gene remnants in species with putatively lost PCSK9.
The red vertical lines indicate the genomic location of the PCSK9 remnants.
Fig 4.
Blast comparison of genomic region between two adjacent genes of pcsk9 (BSND and USP24) in the syntenic block of Camelus Dromedarius and the indicated species with putative loss of pcsk9.
Red blocks indicate regions with significant homology to query (intergenic region of USP24 and BSND in Camel). Numbers indicate the start and end position of the subject sequence (intergenic region of USP24 and BSND in the indicated species with putative loss of pcsk9).
Fig 5.
Phylogenetic trees constructed by Maximum Likelihood method analysis of the coding sequences of PCSKS (bootstrap 1000) in mammalian species belonging to major placental mammalian orders. Orders are indicated by different colors. Branch length scale represents number of 0.05 substitutions per site.
Fig 6.
Phylogenetic analysis of six PCSKs.
The analysis involves the codon sequences of each PCSK’s members from 14 species. Each branch is marked by its PCSK name on the right side. Branch length scale represents 1 substitution per site. The number written at each node represents the bootstrap value indicating the phylogenetic confidence of the tree topology.
Table 1.
Parameter estimates and LRT test of the site models in pcsk1, pcsk3, pcsk5, pcsk7, mbtps1 and pcs.
Fig 7.
Sites under positive selection in the 3D structure of human PCSK9, PCSK1 and FURIN.
A) Homology-based 3D model of PCSK1 catalytic (Red), p-domain (yellow) and part of C-terminal domain (green) (aa 673–731), with sites under positive selection indicated. B) 3D model of PCSK3(FURIN) catalytic (Red) and p-domain (green) (PDB: 4Z2A) and homology-based 3D model of pro-domain (blue) (aa30-108) with sites under positive selection indicated. C) 3D structure of human PCSK9 (PDB: 2PMW) catalytic, pro-domain and v-domain with sites under positive selection indicated.
Table 2.
Parameter estimates for pcsk1, pcsk3, pcsk7 and mbtps1 Clade model C and the result of LRT tests.
Table 3.
Parameter estimates for pcsk1, pcsk5, pcsk7 and pcsk9 branch site model.