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J. Biol. Chem., Vol. 280, Issue 29, 26659-26668, July 22, 2005

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Evolution of Matrix and Bone -Carboxyglutamic Acid Proteins in Vertebrates^*

Vincent Laizé, Paulo Martel¶||, Carla S. B. Viegas, Paul A. Price**, and M. Leonor Cancela

From the Centro de Ciências do Mar (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal, ^¶Instituto de Tecnologia Química e Biológica (ITQB), Universidade Nova de Lisboa, 2781-901 Oeiras, Portugal, ^||Centro de Biomedicina Molecular e Estrutural (CBME), Universidade do Algarve, 8005-139 Faro, Portugal, and ^**Division of Biology, University of California San Diego, La Jolla, California 92093-0368

The evolution of calcified tissues is a defining feature in vertebrate evolution. Investigating the evolution of proteins involved in tissue calcification should help elucidate how calcified tissues have evolved. The purpose of this study was to collect and compare sequences of matrix and bone -carboxyglutamic acid proteins (MGP and BGP, respectively) to identify common features and determine the evolutionary relationship between MGP and BGP. Thirteen cDNAs and genes were cloned using standard methods or reconstructed through the use of comparative genomics and data mining. These sequences were compared with available annotated sequences (a total of 48 complete or nearly complete sequences, 28 BGPs and 20 MGPs) have been identified across 32 different species (representing most classes of vertebrates), and evolutionarily conserved features in both MGP and BGP were analyzed using bioinformatic tools and the Tree-Puzzle software. We propose that: 1) MGP and BGP genes originated from two genome duplications that occurred around 500 and 400 million years ago before jawless and jawed fish evolved, respectively; 2) MGP appeared first concomitantly with the emergence of cartilaginous structures, and BGP appeared thereafter along with bony structures; and 3) BGP derives from MGP. We also propose a highly specific pattern definition for the Gla domain of BGP and MGP.

Received for publication, January 7, 2005 , and in revised form, March 31, 2005.

^* This work was supported in part by Portuguese Science and Technology Foundation Grants PRAXIS/BIA/11159/98, POCTI/34668/Fis/2000, and POCTI/BCI/48748/2002, the latter two including funds from Fundo Europeu de Desenvolvimento Regional and Orçamento do Estado. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequences reported in this paper have been submitted to the DDBJ/GenBank^TM/EBI Data Bank with accession numbers AF525316, AY383483, AY150038, AF526377, AY178836, AY239015, AF144707, AY182238, AY233378, AY182239, AY112747, AF479081, AY298910, AY294644.

Supported by Portuguese Science and Technology Foundation Postdoctoral Fellowship BPD/1607/2000. To whom correspondence should be addressed: Centro de Ciências do Mar, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal. Tel.: 351-289800971; Fax: 351-289818353; E-mail: vlaize{at}ualg.pt.

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