Connexins evolved after early chordates lost innexin diversity

Gap junction channels are formed by two unrelated protein families. Non-chordates use the primordial innexins, while chordates use connexins that superseded the gap junction function of innexins. Chordates retained innexin-homologs, but N-glycosylation prevents them from forming gap junctions. It is puzzling why chordates seem to exclusively use the new gap junction protein and why no chordates should exist that use non-glycosylated innexins to form gap junctions. Here, we identified glycosylation sites of 2388 innexins from 174 non-chordate and 276 chordate species. Among all chordates, we found not a single innexin without glycosylation sites. Surprisingly, the glycosylation motif is also widespread among non-chordate innexins indicating that glycosylated innexins are not a novelty of chordates. In addition, we discovered a loss of innexin diversity during early chordate evolution. Most importantly, lancelets, which lack connexins, exclusively possess only one highly conserved innexin with one glycosylation site. A bottleneck effect might thus explain why connexins have become the only protein used to form chordate gap junctions.

Automated summary

Gap junction channels are formed by two unrelated protein families, with non-chordates using innexins and chordates using connexins. Surprisingly, glycosylated innexins are not unique to chordates, as they are also found in non-chordates. The loss of innexin diversity during early chordate evolution and the presence of only one glycosylated innexin in lancelets, which lack connexins, suggest a bottleneck effect and explain why connexins have become the exclusive protein for chordate gap junctions.