MOLECULAR EVOLUTION OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR - AN EXAMPLE OF MULTIGENE FAMILY IN EXCITABLE CELLS

An extensive phylogenetic analysis of the nicotinic-acetylcholine-rece ptor subunit gene family has been performed by cladistic and phenetic methods. The conserved parts of amino acid sequences have been analyze d by CLUSTAL V and PHYLIP software. The structure of the genes was als o taken in consideration. The results show that a first gene duplicati on may have occurred before the appearance of Bilateria. Three subfami lies then appeared: I-the neuronal alpha-bungarotoxin binding-site sub units (alpha 7, alpha 8); III-the neuronal nicotinic subunits (alpha 2 -alpha 6, beta 2-beta 4), which also contain the muscle acetylcholine- binding subunit (alpha 1); and IV-the muscle non-alpha subunits (beta 1, gamma delta, epsilon) The Insecta subunits (subfamily II) could be orthologous to family III and IV. Several tissular switches of express ion from neuron to muscle and the converse can be inferred from the ex tant expression of subunits and the reconstructed trees. The diversifi cation of the neuronal nicotinic subfamily begins in the stem lineage of chordates, the last duplications occurring shortly before the onset of the mammalian lineage, Such evolution parallels the increase in co mplexity of the cholinergic systems.