title: Intragenic duplication and divergence in the spectrin superfamily of proteins.
abstract: Many structural, signaling, and adhesion molecules contain tandemly repeated amino acid motifs. The alpha-actinin/spectrin/dystrophin superfamily of F-actin-crosslinking proteins contains an array of triple alpha-helical motifs (spectrin repeats). We present here the complete sequence of the novel beta-spectrin isoform beta(Heavy)-spectrin (beta H). The sequence of beta H supports the origin of alpha- and beta-spectrins from a common ancestor, and we present a novel model for the origin of the spectrins from a homodimeric actin-crosslinking precursor. The pattern of similarity between the spectrin repeat units indicates that they have evolved by a series of nested, nonuniform duplications. Furthermore, the spectrins and dystrophins clearly have common ancestry, yet the repeat unit is of a different length in each family. Together, these observations suggest a dynamic period of increase in repeat number accompanied by homogenization within each array by concerted evolution. However, today, there is greater similarity of homologous repeats between species than there is across repeats within species, suggesting that concerted evolution ceased some time before the arthropod/vertebrate split. We propose a two-phase model for the evolution of the spectrin repeat arrays in which an initial phase of concerted evolution is subsequently retarded as each new protein becomes constrained to a specific length and the repeats diverge at the DNA level. This evolutionary model has general applicability to the origins of the many other proteins that have tandemly repeated motifs.
authors.affiliation: Department of Biology, Pennsylvania State University, University Park 16802. gxt5@psu.edu
authors.forename: G H
authors.initials: GH
authors.lastname: Thomas
authors.forename: E C
authors.initials: EC
authors.lastname: Newbern
authors.forename: C C
authors.initials: CC
authors.lastname: Korte
authors.forename: M A
authors.initials: MA
authors.lastname: Bales
authors.forename: S V
authors.initials: SV
authors.lastname: Muse
authors.forename: A G
authors.initials: AG
authors.lastname: Clark
authors.forename: D P
authors.initials: DP
authors.lastname: Kiehart
mesh_terms: D000185:Actinin / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D016189:Dystrophin / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D013049:Spectrin / Q000737:chemistry / Q000235:genetics*
chemical_list: D016189:Dystrophin; D011498:Protein Precursors; D000185:Actinin; D013049:Spectrin