An Evolutionary Analysis of Membrane-Associated Guanylate Kinase Protein Family

Abstract

Gene families come into being through gene and/or genome duplication followed by mutation over time which results in the evolutionarily-related genes having somewhat different nucleotides, amino acids, gene structure, and functions. The membrane-associated guanylate kinase protein family has twelve members in humans: DLG1, DLG2, DLG3, DLG4, CASK, MPP1, MPP2, MPP3, MPP4, MPP5, MPP6, and MPP7. This gene/protein family is characterized by the presence of three specific protein domains: PDZ, SH3, and GUK, all of which aid in protein-protein interactions. These proteins are known to interact with cytoskeletal proteins and also are involved in signal transduction. A characteristic member of this family is the DLG3 gene, is responsible for encoding a synapse associated protein (SAP102). The goal of this study was to better understand the evolutionary relationships among the protein/gene family members. To attain this goal, two evolutionary investigations were undertaken. First, phylogenetic trees, which are the traditional method of analysis, were constructed using the amino acids. This analysis indicated evidence for three distinct sub-groups: group A contained CASK, MPP1, MPP2, MPP6; group B contained MPP3, MPP4, MPP5, MPP7; and group C contained DLG 1, DLG2, DLG3, DLG4. Next, the phylogenetic relationship based on the exon structure was undertaken. Briefly, multiple alignments were combined exon boundary information to generate a visual map of similarities and differences in exon structure among the gene family members. This visualization and its comparison to the traditional phylogenetic analysis will be presented.