Connexin43 orthologues in vertebrates: phylogeny from fish to man

Abstract

The gap junction protein connexin43 (Cx43) is widely expressed in all vertebrate species; however, in ventricular myocardium, Cx43 expression is restricted to mammalian species only, where it provides the molecular correlate for both electrical conduction and synchronization of the repolarization process. The evolutionarily "late" appearance of Cx43 in the heart suggests physiological adaptation to euthermia with its concomitant demands related to increased cardiovascular output. We tested to what extent mammalian Cx43 differs from that of non-mammalian vertebrates and whether Cx43 from hibernating species contains specific sequence characteristics which could be attributed to their non-isothermal life cycle. We cloned the complete coding region of Cx43 from the African green monkey, European hedgehog (hibernator), Russian dwarf hamster, rabbit, European ground squirrel (hibernator) and pig. After sequencing, these were compared to 12 full-length Cx43 sequences present in GenBank (3 fish, 2 frogs, chicken and 6 mammals amongst which there was one other hibernator). Overall identity ranged from 68.7% to 97.7% at the nucleotide level and from 71.6% to 99.7% at the amino acid level. The phylogeny of Cx43 mirrors the general phylogenetic histories of the investigated species to a large extent. From 382 amino acids there were only 6 specific for mammals. There were no substitutions specific for hibernators. In conclusion, mammalian Cx43 is characterized by 6 specific amino acids, and no obvious differences between non-hibernating and hibernating mammals were observed.

The vertebrate connexin family

“…We think this citation describes the puzzlement that many researchers (for ourselves, we could even say confusion) have felt when looking at the different and ever-increasing number of sequences from an increasing number of species, now also including the nonvertebrate group of tunicates [70,73]. A potential reason for the puzzlement could come from the fact that some of the connexins, like orthologs of Cx36 and 43, also have a high degree of conservation in the variable domains, and can therefore easily be recognized across the vertebrates [66,67,74,75]. From this observation, one might assume that this should also be valid for other connexins.…”

Pro-arrhythmogenic potential of immature cardiomyocytes is triggered by low coupling and cluster size

“…Measurements of electrical conductance between the heterologous cell-pairs revealed that the level of coupling was rather poor. Because of a very high amino acid homology of Cx43 proteins in general [25], this low conductance is unlikely to result from species differences. In our model no docking problems have to be expected since rat Cx43 and canine Cx43 showed an overall identity of 97.1%, with only one residue differing in the extracellular domain (data not shown).…”

GJA1mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype

“…Beyer et al [1987] published hydropathicity plots of Cx43, delineating the hydrophobic membrane spanning domains in their model of connexin topology. Since then, various Cx43 topology predictions have been published [Yancey et al, 1989;Laird and Revel, 1990;Yeager and Gilula, 1992;Yeager, 1998;van der Heyden et al, 2004]. Web transmembrane prediction tools HMMTOP, TMHMM, SOSUI, Tmpred, and TopPred (ExPASy Proteomics tools: http://www.…”