Journal of Molecular Evolution

, Volume 40, Issue 2, pp 155–172 | Cite as

Molecular evolution of the nicotinic acetylcholine receptor: An example of multigene family in excitable cells

  • Nicolas Le Novere
  • Jean-Pierre Changeux
Articles

Abstract

An extensive phylogenetic analysis of the nicotinic-acetylcholine-receptor subunit gene family has been performed by cladistic and phenetic methods. The conserved parts of amino acid sequences have been analyzed by CLUSTAL V and PHYLIP software. The structure of the genes was also taken in consideration. The results show that a first gene duplication may have occurred before the appearance of Bilateria. Three subfamilies then appeared: I-the neuronal α-bungarotoxin binding-site subunits (α7, α8); III-the neuronal nicotinic subunits (α2–α6, β2–β4), which also contain the muscle acetylcholine-binding subunit (α1); and IV—the muscle non-α subunits (β1, γ δ, ε). The Insecta subunits (subfamily II) could be orthologous to family III and IV. Several tissular switches of expression from neuron to muscle and the converse can be inferred from the extant expression of subunits and the reconstructed trees. The diversification 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 complexity of the cholinergic systems.

Key words

Nicotinic receptor Ligand-gated channel Multigene family Gene phylogeny 

Abbreviations

α-Bgt

α-bungarotoxin

ACh

acetylcholine

MP

maximum of parsimony

MYA

million years ago

NJ

neighbor-joining

nAChR

nicotinic acetylcholine receptor

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Nicolas Le Novere
    • 1
  • Jean-Pierre Changeux
    • 1
  1. 1.Laboratoire de Neurobiologie MoléculaireParisFrance

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