Intragenic duplication and divergence in the spectrin superfamily of proteins

Many structural, signaling, and adhesion molecules contain tandemlyrepeated amino acid motifs. The alpha-actinin/spectrin/dystrophinsuperfamily of F-actin-crosslinking proteins contains an array of triplealpha-helical motifs (spectrin repeats). We present here the completesequence of the novel beta-spectrin isoform beta(Heavy)- spectrin (beta H).The sequence of beta H supports the origin of alpha- and beta-spectrinsfrom a common ancestor, and we present a novel model for the origin of thespectrins from a homodimeric actin-crosslinking precursor. The pattern ofsimilarity between the spectrin repeat units indicates that they haveevolved by a series of nested, nonuniform duplications. Furthermore, thespectrins and dystrophins clearly have common ancestry, yet the repeat unitis of a different length in each family. Together, these observationssuggest a dynamic period of increase in repeat number accompanied byhomogenization within each array by concerted evolution. However, today,there is greater similarity of homologous repeats between species thanthere is across repeats within species, suggesting that concerted evolutionceased some time before the arthropod/vertebrate split. We propose atwo-phase model for the evolution of the spectrin repeat arrays in which aninitial phase of concerted evolution is subsequently retarded as each newprotein becomes constrained to a specific length and the repeats diverge atthe DNA level. This evolutionary model has general applicability to theorigins of the many other proteins that have tandemly repeated motifs.