Evolutionary selection pressure and family relationships among connexin genes

Abstract

We suggest an extension of connexin orthology relationships across the major vertebrate lineages. We first show that the conserved domains of mammalian connexins (encoding the N-terminus, four transmembrane domains and two extracellular loops) are subjected to a considerably more strict selection pressure than the full-length sequences or the variable domains (the intracellular loop and C-terminal tail). Therefore, the conserved domains are more useful for the study of family relationships over larger evolutionary distances. The conserved domains of connexins were collected from chicken, Xenopus tropicalis, zebrafish, pufferfish, green spotted pufferfish, Ciona intestinalis and Halocynthia pyriformis (two tunicates). A total of 305 connexin sequences were included in this analysis. Phylogenetic trees were constructed, from which the orthologies and the presumed evolutionary relationships between the sequences were deduced. The tunicate connexins studied had the closest, but still distant, relationships to vertebrate connexin 36, 39.2, 43.4, 45 and 47. The main structure in the connexin family known from mammals pre-dates the divergence of bony fishes, but some additional losses and gains of connexin sequences have occurred in the evolutionary lineages of subsequent vertebrates. Thus, the connexin gene family probably originated in the early evolution of chordates, and underwent major restructuring with regard to gene and subfamily structures (including the number of genes in each subfamily) during early vertebrate evolution.

Molecular Diversity of Connexin and Pannexin Genes in the Retina of the ZebrafishDanio rerio

“…The evolutionary relationship of the connexin gene family of the zebrafish Danio rerio has been recently reported in great detail (Eastman et al 2006;Cruciani and Mikalsen 2007). These studies demonstrated a particular complexity of connexins in the teleost, with ∼37 connexins found instead of ∼21 in human or the mouse genome.…”

“…The human ortholog of drCx48.5 is Cx46, a gap junction gene expressed in the murine lens (Paul et al 1991;Pal et al 2000). In contrast, orthologs of drCx39.9 are restricted to fish, amphibian, and birds but cannot be found in mammals (Cruciani and Mikalsen 2007). A single transcript was found for drCx28.6, but the predicted protein of 265 aa is predicted to be encoded by four exons.…”

“…Cx52.6 and Cx55.5 proteins have an amino acid identity score of 45% calculated using the full-length protein sequences. It is now considered that the two connexins are orthologous to either human Cx62 (drCx52.6) or Cx59 (drCx55.5) (Cruciani and Mikalsen 2007).…”

“…A comparison of the connexin gene families from human to zebrafish revealed an expanded family of ∼37 connexins in the zebrafish, with ∼23 zebrafish relatives of 16 mammalian connexins and 14 connexins apparently unique to the zebrafish (Eastman et al 2006;Cruciani and Mikalsen 2007). The expanded gene family is most likely caused by a genome duplication in ancient teleost fish that happened during a short period of time ca.…”

Gap Junctions

“…Gap junctions in prechordates are composed of innexins (Phelan et al 1998;Phelan 2005). In chordates, connexins arose by convergent evolution (Alexopoulos et al 2004), to expand by gene duplication (Cruciani and Mikalsen 2007) into a 21-member gene family. Three innexinrelated proteins, called pannexins, have persisted in vertebrates, although it is not clear if they form intercellular channels (Panchin et al 2000;Bruzzone et al 2003).…”