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MBE Advance Access published online on March 21, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msk007
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© The Author 2006. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted March 16, 2006

Research Article

Origin and Molecular Evolution of Receptor Tyrosine Kinases with Immunoglobulin-like Domains

Julien Grassot 1, Manolo Gouy 2, Guy Perrière 2, and Guy Mouchiroud 1 *

1 Centre de Génétique Moléculaire et Cellulaire, UMR CNRS 5534, Université Claude Bernard - Lyon 1, 43 bd. du 11 Novembre 1918, 69622 Villeurbanne Cedex, France
2 Laboratoire de Biométrie et Biologie Évolutive, UMR CNRS 5558, Université Claude Bernard - Lyon 1, 43 bd. du 11 Novembre 1918, 69622 Villeurbanne Cedex, France

* To whom correspondence should be addressed.
Guy Mouchiroud, E-mail: gmouchir{at}biomserv.univ-lyon1.fr


  Abstract

Receptor tyrosine kinases (RTK) are involved in the control of fundamental cellular processes in metazoans. In vertebrates, RTK could be grouped in distinct classes based on the nature of their cognate ligand and modular composition of their extracellular domain. RTK with Immunoglobulin-like domains (IG-like RTK) encompass several RTK classes and have been found in early metazoans, including sponges. Evolution of IG-like RTK is characterized by extended molecular and functional diversification, which prompted us to study their evolutionary history. For that purpose, a non-redundant dataset including annotated protein sequences of IG-like RTK (n=85) was built, representing 19 species ranging from sponges to humans. Phylogenetic trees were generated from alignment of conserved regions using maximum likelihood approach. Molecular phylogeny strongly suggests that IG-like RTK diversification occurred according to a complex scenario. In particular, we propose that specific cis duplications of a common ancestor to both PDGF receptor (class III) and VEFG receptor (class V) families preceded two trans duplications. In contrast, other IG-like RTK genes, like Musk and PTK7, apparently did not evolve by duplications, whereas FGF receptors (class IV) evolved through two rounds of trans duplications. The proposed model of IG-like RTK evolution is supported by high bootstrap values and by the clustering of genes encoding class III and class V RTK at specific chromosomal locations in mouse and human genomes.

Keywords: Immunoglobulin-like domain; receptor tyrosine kinase; 2R hypothesis.
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