The connexins, gap junction forming proteins, are encoded by a gene family. Sequence comparisons reveal regions of conservation with functional implications for voltage dependence of junctional conductance, junction formation and regulation by phosphorylation. The best connexin tree shows that most gene duplications giving rise to the family occurred early in or before vertebrate divergence. The topology of most deep branches of the tree is uncertain. Evolutionary rates vary for different paralogous connexin genes.