Phylogenetic Analysis of Voltage Gated Ion Channels

Abstract

Voltage-gated ion channels (VGICs) are among the most fascinating proteins because of their function to generate electrical activity in cells and are responsible for many of the most overt manifestations of life. Although VGICs are seen as being critical to animals, particularly those with complex nervous systems, they are relatively old proteins, some of which are well represented in diverse prokaryotes. The present investigation was carried out to highlight the utility of using an evolutionary approach to glean useful information about ion channel function and, by extension, about the properties of other types of proteins. A total of 8 common organism’s protein sequence for VGKC (Voltage-gated potassium channel), VGCC (Voltage-gated calcium channel), and VGSC (Voltage-gated sodium channel) were obtained from Uniprot and subjected to multiple sequence alignment using Praline & ClustalW. The phylogenetic trees were constructed using different methods in MEGA v5.05. The sequence alignment of VGSC proteins of different species revealed no consensus residue. In the sequence alignment of VGKC proteins, five residues (Isoleucine395, Arginine 400, Aspartic Acid 490, Cysteine 502 and Valine 519) were observed to have 70% conservation across different species, while Cysteine 489 was found to be 80% conserved across the species. The sequence alignment of VGCC proteins of different species revealed very little (~50%) conservation across the species. The nature of residue conservation in VGKC reflects that the conservation is majorly for larger amino-acids that help the protein to form channels. The trees obtained for VGKC and VGCC had a remarkable similarity of forming a monophyletic group which was shared by Xenopus or Rattus and Nocardioidaceae or Streptomyces. Contrary to the results of individual trees obtained for VGSC proteins by different methods, the consensus tree generated had a monophyletic group of Homo sapiens and A. gambiae and the group was found to be again very near to prokaryotic VGSC of Streptomyces. The present study is very much of clinical significance because it has revealed that ion channels also exist in lower organisms which are very much related to higher biological systems.