Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates.
The receptor tyrosine kinase (RTK) gene family, involved primarily in cell growth and differentiation, comprises proteins with a common enzymatic tyrosine kinase intracellular domain adjacent to a transmembrane region. The amino-terminal portion of RTKs is extracellular and made of different domains, the combination of which characterizes each of the 20 RTK subfamilies among mammals. We analyzed a total of 7,376 RTK sequences among 143 vertebrate species to provide here the first comprehensive census of the jawed vertebrate repertoire. We ascertained the 58 genes previously described in the human and mouse genomes and established their phylogenetic relationships. We also identified five additional RTKs amounting to a total of 63 genes in jawed vertebrates. We found that the vertebrate RTK gene family has been shaped by the two successive rounds of whole genome duplications (WGD) called 1R and 2R (1R/2R) that occurred at the base of the vertebrates. In addition, the Vegfr and Ephrin receptor subfamilies were expanded by single gene duplications. In teleost fish, 23 additional RTK genes have been retained after another expansion through the fish-specific third round (3R) of WGD. Several lineage-specific gene losses were observed. For instance, birds have lost three RTKs, and different genes are missing in several fish sublineages. The RTK gene family presents an unusual high gene retention rate from the vertebrate WGDs (58.75% after 1R/2R, 64.4% after 3R), resulting in an expansion that might be correlated with the evolution of complexity of vertebrate cellular communication and intracellular signaling.
Institut de Génomique Fonctionnelle de Lyon, Ecole Normale Supérieure de Lyon, UMR5242 CNRS, Université Claude Bernard Lyon I, Lyon, France frederic.brunet@ens-lyon.fr.
Frédéric G
FG
Brunet
Institut de Génomique Fonctionnelle de Lyon, Ecole Normale Supérieure de Lyon, UMR5242 CNRS, Université Claude Bernard Lyon I, Lyon, France.
Jean-Nicolas
JN
Volff
Physiologische Chemie, Biozentrum, University of Würzburg, Am Hubland, and Comprehensive Cancer Center, University Clinic Würzburg, Würzburg, Germany Texas Institute for Advanced Study and Department of Biology, Texas A&M University, College Station, USA.
Manfred
M
Schartl
D000818:Animals; D019143:Evolution, Molecular; D005399:Fishes / Q000235:genetics*; D020440:Gene Duplication; D016678:Genome; D006801:Humans; D051379:Mice; D005810:Multigene Family / Q000235:genetics; D010802:Phylogeny; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D014714:Vertebrates / Q000235:genetics
D020794:Receptor Protein-Tyrosine Kinases
deuterostomes; receptor tyrosine kinase; vertebrates; whole genome duplications