Domain-based approaches to understanding phylogeny and orthology

Domain-based approaches are used in phylogenetic reconstruction and functional identification. Two groups of ionotropic glutamate receptors (iGluR???s) were identified with the topology of the binding core and pore-loop of the eukaryotic iGluR???s. Group 1 has a potassium-like selectivity filter and Group 2 is most closely related to eukaryotic iGluR???s. The relationship among them was investigated in this research. Then, the domain complexity of proteins was analysed on a comprehensive basis. Our results showed that bacterial and archaeal proteins are as complex as eukaryotic proteins in domain abundance, but more promiscuous. Proteins emerged in early stage are also more promiscuous, but with low domain abundance. The possible application of protein comparison based on domain content was also suggested in this research and could be used to help the identification of function and orthology. Therefore, domain-based approaches are proved to be useful in many areas of proteome research, including functional annotation, evolutionary illustration, and protein-protein network construction

Domain-Based Identification and Analysis of Glutamate Receptor Ion Channels and Their Relatives in Prokaryotes

Voltage-gated and ligand-gated ion channels are used in eukaryotic organisms for the purpose of electrochemical signaling. There are prokaryotic homologues to major eukaryotic channels of these sorts, including voltage-gated sodium, potassium, and calcium channels, Ach-receptor and glutamate-receptor channels. The prokaryotic homologues have been less well characterized functionally than their eukaryotic counterparts. In this study we identify likely prokaryotic functional counterparts of eukaryotic glutamate receptor channels by comprehensive analysis of the prokaryotic sequences in the context of known functional domains present in the eukaryotic members of this family. In particular, we searched the nonredundant protein database for all proteins containing the following motif: the two sections of the extracellular glutamate binding domain flanking two transmembrane helices. We discovered 100 prokaryotic sequences containing this motif, with a wide variety of functional annotations. Two groups within this family have the same topology as eukaryotic glutamate receptor channels. Group 1 has a potassium-like selectivity filter. Group 2 is most closely related to eukaryotic glutamate receptor channels. We present analysis of the functional domain architecture for the group of 100, a putative phylogenetic tree, comparison of the protein phylogeny with the corresponding species phylogeny, consideration of the distribution of these proteins among classes of prokaryotes, and orthologous relationships between prokaryotic and human glutamate receptor channels. We introduce a construct called the Evolutionary Domain Network, which represents a putative pathway of domain rearrangements underlying the domain composition of present channels. We believe that scientists interested in ion channels in general, and ligand-gated ion channels in particular, will be interested in this work. The work should also be of interest to bioinformatics researchers who are interested in the use of functional domain-based analysis in evolutionary and functional discovery