Bestrophins are newly identified family of Cl- channels. To clarify the phylogenetic relationship among bestrophin homologues and to statistically evaluate functional divergence between bestrophin subfamilies, a comprehensive bioinformatics- phylogenetic study of the bestrophin protein family was performed. Phylogenetic analysis of the bestrophin homologues reveals existence of four evolutionary conserved family members in mammals, with high homology to the human VMD2, VMD2- L1 to L3 proteins, suggesting that the evolution of the bestrophin family has been facilitated by gene duplication. Furthermore, we show that functional divergence had occurred between bestrophin subfamilies after gene duplication in the lineage leading to mammals, and residues critical for the functional divergence between bestrophins 1 and 4 (VMD2 and VMD2-L2) were predicted. In addition multiple amino acid sequence alignments of bestrophin orthologous revealed motifs conserved across family members that might be important for structure and function of the protein.

Supported by DFG Schr752/2-2

SFB 699 A7