Evidence for positive selection in the C-terminal domain of the cholesterol metabolism gene PCSK9 based on phylogenetic analysis in 14 primate species.

ABSTRACT:

Background

Cholesterol homeostasis is maintained through finely tuned mechanisms regulating intestinal absorption, hepatic biosynthesis and secretion as well as plasma clearance. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted enzyme of the serine protease family that reduces cellular uptake of plasma low-density lipoprotein (LDL) cholesterol by promoting LDL receptor (LDL-R) degradation. Species-specific positive selection has been noted in the LDLR promoter, leading to differential expression of LDLR among primates. Whether PCSK9 experienced significant selective pressure to maintain a functional relationship with its target protein, LDL-R, is unknown.

Methodology/principal findings

We compiled the sequences of the coding regions of PCSK9 from 14 primat

SUBMITTER: Ding K 

PROVIDER: S-EPMC2034530 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature