Connexin43 orthologues in vertebrates: phylogeny from fish to man

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.