CHILOSCYLLIUM PLAGIOSUM LOW-DENSITY-LIPOPROTEIN RECEPTOR - EVOLUTIONARY CONSERVATION OF 5 DIFFERENT FUNCTIONAL DOMAINS

All five functional domains of the low-density lipoprotein (LDL) recep tor were assembled in their modern form more than 450 million years ag o, as revealed from the cloning and sequencing of an LDL receptor cDNA from Chiloscyllium plagiosum (banded cat shark). The shark LDL recept or has the same overall architecture as the mammalian and amphibian co unterparts. Each of the seven cysteine-rich repeats in the ligand bind ing domain resembles its counterpart in the human LDL receptor more th an it does the other repeats in the shark receptor as suggested by the presence of unique ''signature'' sequences, indicating that these rep eats had already acquired their independent structures by the time of shark development. Furthermore, amino acid sequences of the entire lig and binding domain of shark LDL receptor show 35% identity over a stre tch of 294 residues with a Lymnaea stagnalis G-protein-linked receptor (LSGLR). The region of homology between these unrelated proteins incl udes conservation of most of the unique characteristics of the cystein e-rich repeats of LDL receptor at the expected positions in LSGLR. The results presented are consistent with the hypothesis that all seven r epeats in the ligand binding domain of LDL receptor may have been lift ed directly from an ancestral gene instead of being evolutionary dupli cations of a single repeat recruited by the primitive LDL receptor fro m another gene.