Journal of Molecular Evolution

, Volume 34, Issue 5, pp 416-448

First online:

Evolution of EF-hand calcium-modulated proteins. II. Domains of several subfamilies have diverse evolutionary histories

  • Susumu NakayamaAffiliated withDepartment of Biology, University of Virginia
  • , Nancy D. MoncriefAffiliated withDepartment of Mammalogy, Virginia Museum of Natural History
  • , Robert H. KretsingerAffiliated withDepartment of Biology, University of Virginia

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In the first report in this series we described the relationships and evolution of 152 individual proteins of the EF-hand subfamilies. Here we add 66 additional proteins and define eight (CDC, TPNV, CLNB, LPS, DGK, 1 F8, VIS, TCBP) new subfamilies and seven (CAL, SQUD, CDPK, EFH5, TPP, LAV, CRGP) new unique proteins, which we assume represent new subfamilies.

The main focus of this study is the classification of individual EF-hand domains. Five subfamilies—calmodulin, troponin C, essential light chain, regulatory light chain, CDC31/caltractin-and three uniques—call, squidulin, and calcium-dependent protein kinase-are congruent in that all evolved from a common four-domain precursor. In contrast calpain and sarcoplasmic calcium-binding protein (SARC) each evolved from its own one-domain precursor. The remaining 19 subfamilies and uniques appear to have evolved by translocation and splicing of genes encoding the EF-hand domains that were precursors to the congruent eight and to calpain and to SARC.

The rates of evolution of the EF-hand domains are slower following formation of the subfamilies and establishment of their functions. Subfamilies are not readily classified by patterns of calcium coordination, interdomain linker stability, and glycine and proline distribution. There are many homoplasies indicating that similar variants of the EF-hand evolved by independent pathways.

Key words

EF-hand Calcium binding protein Gene duplication Congruence Domain transposition Calmodulin Troponin C Light chains of myosin Parvalbumin S100 Calpain