Meeting Abstract
P1.164 Saturday, Jan. 4 15:30 Reconstructing the evolution of ancestral gap junction proteins BOND, S.R.*; BAXEVANIS, A.D.; Genome Technology Branch, Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health; Genome Technology Branch, Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health steve.bond@nih.gov
Gap junctions (GJs) are a nearly ubiquitous feature of metazoan life, coupling the cytoplasm of adjacent cells into a partially selective syncytium. The range of physiological and pathophysiological processes that GJs partake in is extensive – a feature that is mirrored by an equally extensive diversity in the primary sequence of GJ-forming proteins. A particular curiosity is the presence of two distinct families of GJ proteins within the animal kingdom. In chordates, connexins (Cxs) are responsible for coupling adjoining cells, while the “invertebrate analogs of connexins”, namely innexins (Inxs), perform the function across most of the remaining phyla. While the three-dimensional structures of Inxs and Cxs are thought to be quite similar, they share very little identity at the sequence level, making it difficult to infer homology with any level of statistical rigor. In the current study, we explore the evolutionary relationship between Inxs and Cxs, making use of newly released whole-genome sequence data to include GJ proteins from all major metazoan phyla. Structural features of these proteins are used to guide multiple sequence alignments, and ancestral states are reconstructed as position-specific scoring matrices (PSSMs) from groups of closely related sequences using partial-order sequence graphs, Bayesian inference, and maximum likelihood approaches. Sequential profile-profile alignments then allow us to progressively step down through deeper phylogenetic nodes to the inferred base (i.e., the last common ancestor) of both the Inx and Cx families. It is from these basal PSSMs that we finally calculate the probability of Inx and Cx homology.
