Intragenic duplication and divergence in the spectrin superfamily of proteins

Graham H. Thomas, E. Claire Newbern, Carol C. Korte, Mark A. Bales, Spencer V. Muse, Andrew G. Clark, Daniel P. Kiehart

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54 Scopus citations


Many structural, signaling, and adhesion molecules contain tandemly repealed amino acid motifs. The α-actinin/spectrin/dystrophin superfamily of F-actin-crosslinking proteins contains an array of triple α-helical motifs (spectrin repeats). We present here the complete sequence of the novel β- spectrin isoform β(Heavy)-spectrin (β(H)). The sequence of β(H) supports the origin of α- and β-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.

Original languageEnglish (US)
Pages (from-to)1285-1295
Number of pages11
JournalMolecular biology and evolution
Issue number12
StatePublished - 1997

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


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