MBE Advance Access originally published online on March 21, 2006
Molecular Biology and Evolution 2006 23(6):1232-1241; doi:10.1093/molbev/msk007
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Article |
Origin and Molecular Evolution of Receptor Tyrosine Kinases with Immunoglobulin-Like Domains
* Centre de Génétique Moléculaire et Cellulaire, UMR Centre National de la Recherche Scientifique 5534, Université Claude Bernard—Lyon 1, Villeurbanne, France; and Laboratoire de Biométrie et Biologie Évolutive, UMR Centre National de la Recherche Scientifique 5558, Université Claude Bernard—Lyon 1, Villeurbanne, France
E-mail: gmouchir{at}biomserv.univ-lyon1.fr.
 |
Abstract |
|---|
 TOP Abstract IntroductionMaterial and MethodsResults and DiscussionConclusionsSupplementary MaterialAcknowledgementsReferences |
|---|
Receptor tyrosine kinases (RTKs) 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 nonredundant data set 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 platelet-derived growth factor receptor (class III) and vascular endothelial growth factor 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 fibroblast growth factor 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 RTKs at specific chromosomal locations in mouse and human genomes.
Key Words: immunoglobulin-like domain • receptor tyrosine kinase • 2R hypothesis
|
Introduction |
|---|
|
TOPAbstractIntroductionMaterial and MethodsResults and DiscussionConclusionsSupplementary MaterialAcknowledgementsReferences |
|---|
Receptor tyrosine kinases (RTKs) are metazoan-specific plasma membrane receptors that control multiple fundamental cellular processes during development and in adult life, such as cell cycle, migration, metabolism, survival, proliferation, and differentiation. RTKs are transmembrane proteins sharing two major functional domains: the extracellular ligand-binding domain and the intracellular tyrosine kinase domain that distinguishes RTK from all other receptors. In vertebrates, especially in human and mouse, molecular phylogeny analysis of amino acid sequences of the conserved kinase domain was used to define an RTK classification that shows good concordance with the modular structure of extracellular domains (Hubbard and Till 2000
; Robinson, Wu, and Lin 2000; Kostich et al. 2002).
Genome sequencing as well as specific investigations point to early appearance of RTK in metazoans and intense diversification within some RTK subfamilies. The first RTK likely arose from fusion of an epidermal growth factor (EGF)–like domain and a cytoplasmic tyrosine kinase before the appearance of animals (King and Caroll 2001). In the freshwater sponge Ephydatia fluviatilis, nine putative RTK genes were identified following reverse transcription–polymerase chain reaction amplification, of which four are related to the RTK genes found in Drosophila melanogaster and vertebrates: the Musk, ephrin (Eph), Ros, and EGF receptors (Suga, Kato, and Miyata 2001). Besides well-conserved RTK subfamilies, other RTK genes have been found in early metazoans, Caenorhabditis elegans, and D. melanogaster, and several have no orthologs or mammalian paralogs (Plowman et al. 1999; Popovici et al. 1999; Adams et al. 2000; Miller and Steele 2000; Vicogne et al. 2003). Furthermore, sequencing projects are generating large amounts of predicted RTK sequences that may be difficult to annotate based on the current classification, raising the question of whether they represent a novel class of RTK or simply result from specific evolutionary history. In this respect, understanding RTK evolution would help global RTK classification, which in turn might facilitate annotation of new RTK sequences and the use of new model organisms to study human RTK function.
As mentioned above, the number and diversity of RTK genes sharply increased during the metazoan evolution, resulting in complex nomenclature and phylogeny. This is especially true for Eph receptors and RTK with immunoglobulin-like domains (IG-like RTK) that appeared during the early stages of animal evolution and represent the most abundant RTK classes in vertebrates (Muller et al. 1999; Drescher 2002). Due to widespread distribution within the genome, RTK genes may then provide a useful tool for evolutionary studies, especially on the extent of gene duplication during metazoan evolution and its contribution to genome complexity. Phylogenetic analyses have been carried out for Eph receptors and IG-like RTK, but they used either selected receptors or limited sets of species (Rousset et al. 1995; Parichy et al. 2000; Drescher 2002; Satou et al. 2003). Although these studies suggested a common evolutionary origin within each receptor family, underlying mechanisms are still elusive. This prompted us to establish a global and comprehensive molecular phylogeny for RTK. For this purpose, we concentrated here on the evolution of IG-like RTK genes. We first established a representative data set of protein sequences from IG-like RTK among which about one-third precede tetrapods/teleosts divergence. Phylogeny analyses were performed using a maximum likelihood algorithm allowing to build large phylogenies in a reasonable computing time (Guindon and Gascuel 2003). Our results support a monophyletic origin of IG-like RTK, at least for classes III (platelet-derived growth factor [PDGF] receptors), IV (fibroblast growth factor [FGF] receptors), and V (vascular endothelial growth factor [VEGF] receptors) and point to gene duplication/loss events that resulted in the current repertoire.
|
Material and Methods |
|---|
|
TOPAbstractIntroductionMaterial and MethodsResults and DiscussionConclusionsSupplementary MaterialAcknowledgementsReferences |
|---|
First, a data set of IG-like RTK protein sequences was established from the RTKdb database (Grassot, Mouchiroud, and Perrière 2003
), which was developed by collecting RTK sequences from the UniProt collection (Bairoch et al. 2005) and arranging them into classes. Information on the RTKdb database can be accessed at http://pbil.univ-lyon1.fr/RTKdb/. Additional sequences were collected through TBlastN (Altschul et al. 1997) searches in the European Molecular Biology Laboratory (Kanz et al. 2005), Ensembl (Hubbard et al. 2005), and Joint Genome Institute (http://www.jgi.doe.gov/) databases. For that purpose, a first search was performed using vertebrate IG-like RTK sequences as baits, and resulting hits were recursively used for new runs as long as more members of the RTK family were obtained. The resulting data set contained 111 complete sequences of RTK with IG-like domains from various organisms. From this data set, 81 sequences were from posttetrapods/postteleosts divergence species. Sequences from Rattus norvegicus and Mus musculus were removed because they did not add relevant information to that brought by human sequences. This reduced the data set to 85 sequences (table 1).
|
Alignments were performed using MUSCLE (Edgar 2004
) with default parameter values, and reliably aligned regions were selected with Gblocks (Castresana 2000). The minimum length for conserved blocks was set to five residues, and we choose to keep positions containing gaps only if less than 50% of the sequences had a gap. Resulting alignments were bootstraped 1,000 times with the program SEQBOOT from the PHYLIP package (Felsenstein 1989). Phylogenetic trees were computed with the maximum likelihood method implemented in PhyML (Guindon and Gascuel 2003). The Jones-Taylor-Thornton model of amino acid substitution was used (Jones, Taylor, and Thornton 1992). Across-site rate variation was modeled by a gamma distribution with four classes of substitution rates. Alpha parameter of the gamma distribution was estimated by PhyML. The addBootstrap program (distributed upon request by Manolo Gouy) allowed us to merge bootstrap scores and branch lengths in a single tree. At last, phylogenetic trees were drawn with NJplot (Perrière and Gouy 1996). Computations were performed on the IN2P3 Linux cluster containing more than 1,000 CPUs. All alignments and trees can be downloaded at ftp://pbil.univ-lyon1.fr/pub/datasets/MBE06. Species are denoted as follows, with a UniProt-like nomenclature: ANOGA, Anopheles gambiae; BRARE, Brachydanio rerio; CAEEL, C. elegans; CIOIN, Ciona intestinalis; COTJA, Coturnix coturnix japonica; DROME, D. melanogaster; DUGJA, Dugesia japonica; EPHFL, E. fluviatilis; FUGRU, Fugu rubripes; CHICK, Gallus gallus; GEOCY, Geodia cydonium; HALRO, Halocynthia roretzi; HUMAN, Homo sapiens; HYDAT, Hydra attenuata; NOTVI, Notophthalmus viridescens; PLEWA, Pleurodeles waltlii; STRPU, Strongylocentrotus purpuratus; TORCA, Torpedo californica; and XENLA, Xenopus laevis.
|
Results and Discussion |
|---|
|
TOPAbstractIntroductionMaterial and MethodsResults and DiscussionConclusionsSupplementary MaterialAcknowledgementsReferences |
|---|
Early Divergence of Musk/PTK7 and Other RTK with IG-Like Domains
In order to establish a relevant molecular phylogeny, we focused our investigations on IG-like RTK classes found in all investigated metazoan species, thereby excluding classes VII (Rikke, Murakami, and Johnson 2000
), VIII (Jaaro et al 2001), and IX (J. Grassot and G. Mouchiroud, unpublished data). The conserved regions of IG-like RTK from 23 species, among which eight had their genome completely sequenced, were used to compute the phylogenetic tree shown in figure 1. This tree was rooted with class II RTK (insulin-related receptors) because these receptors were also present at the very beginning of RTK evolution (Aguinaldo et al. 1997). It shows two major groups corresponding to RTK related to class XVII and class XIX and RTK related to classes III, IV, and V. This dichotomy has a bootstrap support of 86%, which suggests early divergence of both groups of IG-like RTK. Figure 1 also shows a poorly resolved group of RTK sequences of three types: class XIX, class XVII, and a group of receptors mainly found in sponges (GCTK_GEOCY, RTK2_GEOCY, RTK_GEOCY, and EPTK_EPHFL) and ascidians (RTK1_CIOIN and RTK3_CIOIN). Grouping of the H. attenuata sequence with all PTK7 sequences is supported by high bootstrap value (96%), which indicates that this sequence is homologous to PTK7. Interestingly, PTK7 is a kinase-defective RTK (Mossie et al. 1995), which suggests that strong conservation of this receptor during metazoan evolution was due to constraint on biological rather than catalytic function of the molecule. Indeed, it was recently shown that PTK7 is an important regulator of cell polarity in drosophila and mammals (Lu et al. 2004). Similar to PTK7 sequences, class XIX RTK (Musk) grouped in a single cluster. Other RTK sequences shown in figure 1 segregated in a heterogeneous cluster of sequences, including both porifera (G. cydonium) and deuterostomes (C. intestinalis), yet we could not determine with significant bootstrap support the evolutionary relationships between these RTKs. More extensive taxonomical sampling is required to clarify this point.
|
A Common Ancestor to Subclasses III, IV, and V
Contrasting with the low diversification among class XVII, class XIX, and closely related RTKs, the phylogeny shown in figure 1 suggests complex mechanisms leading to the generation of class III, class IV, and class V RTKs. By combining molecular phylogeny of human IG-like RTK and analysis of exon/intron structure of corresponding genes, Rousset et al. (1995)
proposed that class III, class IV, and class V RTK genes evolved from a single ancestor gene by successive duplications. Further phylogenetic analyses supported this model, yet they focused on restricted set of sequences (Heino et al. 2001; J. Gu and X. Gu 2003; Satou et al. 2003). The present phylogenetic tree, generated with an extended data set, clearly confirms that a duplication event first permitted divergence between class IV and the cluster of class III and class V RTKs. This event may be dated before the protostomes/deuterostomes split due to the presence of protostome sequences in the class IV and in the cluster of classes III and V.
Evolution of the FGF Receptors (Class IV)
All FGF receptors grouped in a single cluster. However, sequences from species exhibiting four FGF receptor genes grouped together, and were clearly distinguishable from other FGF sequences, found in protostomes (nematode: EG15_CAEEL; planarian: FGR1_DUGJA and FGR2_DUGJA; insects: FGR1_DROME, FGR2_DROME, and RTK2_ANOGA), ascidian (C. intestinalis: FGR_CIOIN; sea squirt: FGR_HALRO), echinoderms (sea urchin: FGR_STRPU), and cnidarians (hydra: FGR_HYDAT). Additional phylogenies were performed using restricted combinations of the latter sequences (i.e., by specifically removing some of them from the whole data set). They confirmed grouping of these sequences at the base of the FGF receptor tree (data not shown), indicating that gross topology of FGF receptors as shown in figure 1 was robust and likely not influenced by the long-branch attraction phenomenon. Although divergence order could not be precisely determined, some of these sequences suggest key dates for the evolution of this RTK class. Indeed, ascidian sequences of C. intestinalis and H. roretzi are branched at the base of the tree of FGF receptor sequences, suggesting that the duplication events leading to diversification seen in human occurred after the chordates/urochordates divergence.
As noted above, other class IV sequences, from species that descend from the tetrapods/teleosts split, grouped in four clusters, consistent with human FGF receptor classification (Robinson, Wu, and Lin 2000). For these species, alignments computed on the whole set of sequences led to a phylogeny whose bootstrap values are not significant (fig. 1). In order to obtain a better resolved phylogeny, we needed to increase the number of useful sites in the alignments. For that purpose, we used alignments computed—and then filtered by Gblocks—only on the sequences belonging to class IV. The resulting phylogeny showed a symmetrical topology supported by high bootstrap values (
80%), which strongly suggests that FGF receptor diversification after the chordates/urochordates split resulted from two successive duplication events: the first duplication led to FGR1/2 and FGR3/4 groups, and the second one separated FGR1 from FGR2 and FGR3 from FGR4 (fig. 2A). A similar topology was observed by Coulier et al. (1997), who suggested that FGF receptors evolved through successive duplications in vertebrates. All duplications likely occurred between the chordates/urochordates and tetrapods/teleosts splits because fish sequences are present in all four groups (FGR1/2/3/4). Interestingly, chordate FGF receptors are found within paralogous chromosome regions that were supposed to evolve from a common ancestral region through several duplications (Pebusque et al. 1998). In this respect, robustness of the phylogenetic tree shown in figure 2A clearly supports a duplication scheme consistent with the "2R" hypothesis of two rounds of large-scale duplication in the lineage leading to the vertebrates (Ohno 1970; Taylor and Brinkmann 2001; Wolfe 2001).
|
Evolutionary Relationship Between Class III and Class V
Three sequences from nematode (TKR_CAEEL otherwise known as T17A3.1, F5V3_CAEEL, or F59F3.1 and F5V4_CAEEL or F59F3.5) grouped at the root of the cluster comprising classes III and V (fig. 1). Several data set were tested from which sequences shown in figure 1 were removed according to various combinations. All resulting phylogenies supported branching of the three C. elegans sequences at the base of classes III/V cluster, which also rules out possible errors due to long-branch attraction phenomenon (data not shown). These sequences have been previously assigned to the VEGF receptor family, based on conservation of the cysteine residues delimiting IG-like domains (Plowman et al. 1999
; Popovici et al. 1999), and corresponding loci are now referred to as ver-1, ver-3, and ver-4, respectively. As previously noted (Popovici et al. 2002), these sequences did not show strong phylogenetic relationships with human or chordates VEGF receptors, which raises the possibility that they are related to the ancestral sequence to classes III and V. Alternatively, F5V3_CAEEL, F5V4_CAEEL, and TKR_CAEEL could represent "bona fide" VEGF receptors, and the phylogeny shown in figure 1 could result from the higher evolutionary rate of C. elegans genes compared to that of other metazoa (Aguilnado et al. 1997). Vascular-endothelial-cell/platele-derived growth factor (VEPG) (or PDGF/VEGF) is the only gene in D. melanogaster genome that encodes RTK related to vertebrates PDGF and VEGF receptors (Duchek et al. 2001; Heino et al. 2001). Interestingly, VEPG was also found in A. gambiae genome (Holt et al. 2002). The presence of seven predicted IG-like domains in extracellular region as well as its role in blood cell development and migration suggested that VEPG is closer to VEGF receptors than PDGF receptors (Duchek et al 2001, Heino et al. 2001; Cho et al. 2002). Our results are in agreement with this suggestion, yet bootstrap value was not significant for this branch (39%).
Class III and class V sequences from chordates grouped in two clusters with high bootstrap values (100% and 94%, respectively), suggesting independent evolution from a common ancestor (see above). The divergence occurred after the protostomes/deuterostomes separation by duplication due to the absence of protostome sequences in classes III and V. Additional duplications occurred before the tetrapods/teleosts divergence, as suggested by the fact that all sampled tetrapods and fishes have the same class III and class V repertoires. Within class V, vertebrate RTK sequences grouped into VGR1, VGR2, and VGR3 subgroups, consistent with previous classification (Shibuya 2002). Interestingly, VGR_CIOIN, from the ascidian C. intestinalis, segregated with class V sequences, which suggests that classes III and V diverged before the apparition of urochordates. In contrast, no C. intestinalis class III sequence could be identified. Collectively, the data suggest that VGR_CIOIN is a class V RTK and that its paralog (class III) was lost in the ascidian lineage after duplication of the class III/class V ancestral gene (Leveugle et al. 2004).
Duplication and Loss of Genes During Evolution of Class III and Class V RTKs
Unlike class IV whose diversification could be explained by two successive rounds of duplications, diversification of classes III and V after the chordates/urochordates split follows a more complex scenario. In humans, clustering of PGDS (now referred to as PDGF receptor-alpha), KIT (the cellular homolog of v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene), and VGR (VEGF receptor)-2 on chromosome 4q; PGDR (now referred as to PGDF receptor-beta), CSF-1R (colony-stimulating-factor 1 receptor, or Fms), and VGR3 on chromosome 5q; and FLT3 (Fms-like tyrosine kinase 3) and VGR1 on chromosome 13q suggested evolution of these eight genes from a common ancestor gene through several duplications and specific gene losses (Rousset et al. 1995; Shibuya 2002; J. Gu and X. Gu 2003). Our result clearly supports the existence of an ancestor cluster of three genes that gave rise to PDGF receptors (PGDS, PGDR), FMS/KIT/FLT3 receptors, and VEGF receptors (VGR1, VGR2, VGR3), respectively. According to this scenario, cis duplication of an ancestral gene (VEPG like) first generated precursors of classes V and III. Then, class III precursor underwent another cis duplication event leading to a putative precursor cluster (fig. 3A). As discussed above, the first cis duplication (D1) occurred before the chordate/urochordate split, whereas the second one (D2) occurred after.
|
The phylogeny of class III RTK supports duplication of a chromosome fragment leading to IG-like RTK clusters on human chromosomes 4q12 (KIT, PDGS, and VGR2) and 5qter (FMS, PDGR, and VGR3). The phylogeny of class V RTK is also in agreement with this possibility (fig. 1). However, the bootstrap values determining this scenario are low. We attempted to clarify the class V RTK phylogeny by aligning only class V sequences, which resulted in more sites. Then, higher and significant bootstrap values were obtained for each tree branch, supporting common origin of human VGR2 and VGR3 (fig. 2B). Consequently, two models may be proposed for the evolution of the putative ancestor cluster (fig. 3B). Both involve two trans duplications (D3 and D4), generating the IG-like RTK clusters found on chromosomes 4 and 5. This evolution scheme is consistent with the location of both clusters in paralogons between human chromosomes 4 and 5 (Lundin 1993
; Perez 2003). Concerning Flt3/VGR1 genes, a parsimonious scenario involves loss of a class III member (fig. 3B, left), whereas a scenario consistent with the 2R hypothesis involves a second round of duplication followed by loss of one cluster and loss of a class III member (missing sixth member) in the remaining cluster (fig. 3B, right). In order to test these hypotheses, we reasoned that some of the genes around class III and class V RTKs in 4q12, 5q33, and 13q12.2/3 might be present elsewhere in the human genome, thereby marking a putative paralogy region with 13q12.2/3. Interestingly, the three clusters include ParaHox genes (GSH/Cdx) in 5' of class III RTK genes and two groups of related sequences in 3' of class V RTK genes, confirming the paralogy of these chromosomal regions (Minguillon and Garcia-Fernandes 2003). Similarity search was performed with each sequence in the human genome (http://www.ensembl.org/index.html). Our results first confirmed paralogy of 4q12, 5q33, and 13q12 (supplementary fig. 1, Supplementary Material online). Interestingly, a few genes were found that significantly matched (E < 10–15) paralogous genes on the three chromosomes, but these genes were dispersed within the genome and did not enable to define a specific genomic fragment. Then, we considered genomic regions showing significant homologies with several genes found in the vicinity of class III and class V RTKs in 4q12, 5q33, and 13q12. This investigation pointed to possible homology between these regions and a region found on chromosome 19, in 19q13 (supplementary fig. 1 and supplementary table 1, Supplementary Material online). The HIF3A, GLTSCR1, and MYH14 genes found in 19q13 identify a cluster similar to those found in 3' of class V RTK genes in the paralogous regions on chromosomes 4, 5, and 13. Interestingly, no RTK sequence was found in 19q13, nor paralogs to genomic-screened homeobox or Cdx. Cdx and collagen type IV genes have been found to define a homology region between chromosome 13q12/q34 and chromosome Xq13/q23 (Minguillon and Garcia-Fernandes 2003). Thus, remains of a paralogon between chromosomes 4, 5, and 13 might be shared by chromosomes 19 and X in humans. In summary, the data support the hypothesis of two trans duplications accompanied by a chromosomal fragment loss (fig. 3B, right) to explain the current localization of class III and V RTK genes in the human genome. A similar conclusion was reached after analyzing the chromosomal location of mouse class III and class V RTK genes (data not shown). |
Conclusions |
|---|
|
TOPAbstractIntroductionMaterial and MethodsResults and DiscussionConclusionsSupplementary MaterialAcknowledgementsReferences |
|---|
Combined to data from the literature, the present study enabled us to propose a comprehensive scenario of IG-like RTK evolution (fig. 4). The main families of IG-like RTK emerged before the chordate/urochordate split. Further chordate-specific duplication events resulted in diversification of the IG-like RTK family in agreement with the 2R hypothesis. Whereas molecular phylogeny and chromosome synteny provided strong evidence for a shared ancestry of class III and V RTKs, evolutionary relationships between class IV RTK and class III/V RTK need to be clarified. More RTK sequences from invertebrates are needed for this, which should help to refine the evolutionary history of IG-like RTK.
|
|
Supplementary Material |
|---|
|
TOPAbstractIntroductionMaterial and MethodsResults and DiscussionConclusionsSupplementary MaterialAcknowledgementsReferences |
|---|
Supplementary figure 1 and table 1 are available at Molecular Biology and Evolution online (http://www.mbe.oxfordjournals.org/).
|
Acknowledgements |
|---|
|
TOPAbstractIntroductionMaterial and MethodsResults and DiscussionConclusionsSupplementary MaterialAcknowledgementsReferences |
|---|
We gratefully acknowledge IN2P3 for the computer resources. This work was supported by the Centre National de la Recherche Scientifique, by a "Ligue Nationale Contre le Cancer" grant (program "Equipe Labellisée" for G.M.'s group), and by a fellowship from IFR 41 entitled: "Building specific tools for bioinformatic studies of modular polypeptide sequences." J.G. was recipient of a fellowship from the Ministére de l'Education Nationale, de la Recherche, et de la Technologie.
|
Footnotes |
|---|
William Martin, Associate Editor
|
References |
|---|
|
TOPAbstractIntroductionMaterial and MethodsResults and DiscussionConclusionsSupplementary MaterialAcknowledgementsReferences |
|---|
Adams, M. D., S. E. Celniker, R. A. Holt et al. (192 co-authors). 2000. The genome sequence of Drosophila melanogaster. Science 287:2185–2195.
Aguinaldo, A. M., J. M. Turbeville, L. S. Linford, M. C. Rivera, J. R. Garey, R. A. Raff, and J. A. Lake. 1997. Evidence for a clade of nematodes, arthropods and other moulting animals. Nature 387:489–493.[CrossRef][Medline]
Altschul, S. F., T. L. Madden, A. A. Schäffer, J. Zhang, Z. Zhang, W. Miller, and D. J. Lipman. 1997. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25:3389–3402.
Bairoch, A., R. Apweiler, C. H. Wu et al. (15 co-authors). 2005. The universal protein resource (UniProt). Nucleic Acids Res. 33:D154–D159.
Castresana, J. 2000. Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol. Biol. Evol. 17:540–552.
Cho, N. K., L. Keyes, E. Johnson, J. Heller, L. Ryner, F. Karim, and M. A. Krasnow. 2002. Developmental control of blood cell migration by the Drosophila VEGF pathway. Cell 108:865–876.[CrossRef][Medline]
Coulier, F., P. Pontarotti, R. Roubin, H. Hartung, M. Goldfarb, and D. Birnbaum. 1997. Of worms and men: an evolutionary perspective on the fibroblast growth factor (FGF) and FGF receptor families. J. Mol. Evol. 44:43–56.[CrossRef][Web of Science][Medline]
Drescher, U. 2002. Eph family functions from an evolutionary perspective. Curr. Opin. Genet. Dev. 4:397–402.
Duchek, P., K. Somogyi, G. Jekely, S. Beccari, and P. Rorth. 2001. Guidance of cell migration by the Drosophila PDGF/VEGF receptor. Cell 107:17–26.[CrossRef][Web of Science][Medline]
Edgar, R. C. 2004. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32:1792–1797.
Felsenstein, J. 1989. PHYLIP—phylogeny inference package. Version 3.2. Cladistics 5:164–166.
Grassot, J., G. Mouchiroud, and G. Perrière. 2003. RTKdb: database of receptor tyrosine kinase. Nucleic Acids Res. 31:353–358.
Gu, J., and X. Gu. 2003. Natural history and functional divergence of protein tyrosine kinases. Gene 317:49–57.[CrossRef][Web of Science][Medline]
Guindon, S., and O. Gascuel. 2003. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst. Biol. 5:696–704.
Heino, T. I., T. Karpanen, G. Wahlstrom, M. Pulkkinen, U. Eriksson, K. Alitalo, and C. Roos. 2001. The Drosophila VEGF receptor homolog is expressed in hemocytes. Mech. Dev. 109:69–77.[CrossRef][Medline]
Holt, R. A., G. M. Subramanian, A. Halpern et al. (120 co-authors). 2002. The genome sequence of the malaria mosquito Anopheles Gambiae. Science 298:129–149.
Hubbard, S. R., and J. E. Till. 2000. Protein tyrosine kinase structure and function. Annu. Rev. Biochem. 69:373–398.[CrossRef][Web of Science][Medline]
Hubbard, T., D. Andrews, M. Caccamo et al. (52 co-authors). 2005. Ensembl 2005. Nucleic Acids Res. 33:D447–D453.
Jaaro, H., G. Beck, and S. G. Conticello. 2001. Evolving better brains: a need for neurotrophins? Trends Neurosci. 24:79–85.[CrossRef][Medline]
Jones, D. T., W. R. Taylor, and J. M. Thornton. 1992. The rapid generation of mutation data matrices from protein sequences. Comput. Appl. Biosci. 8:275–282.
Kanz, C., P. Aldebert, N. Althorpe et al. (32 co-authors). 2005. The EMBL nucleotide sequence database. Nucleic Acids Res. 33:D29–D33.
King, N., and S. B. Caroll. 2001. A receptor tyrosine kinase from choanoflagellates: molecular insights into early animal evolution. Proc. Natl. Acad. Sci. USA 98:15032–15037.
Kostich, M., J. English, V. Madison, F. Gheyas, L. Wang, P. Qiu, J. Greene, and T. M. Laz. 2002. Human members of the eukaryotic protein kinase family. Genome Biol. 3:9.
Leveugle, M., K. Prat, C. Popovici, D. Birnbaum, and F. Coulier. 2004. Phylogenetic analysis of Ciona intestinalis gene superfamilies supports the hypothesis of successive gene expansions. J. Mol. Evol. 58:168–181.[CrossRef][Web of Science][Medline]
Lu, X., A. G. Borchers, C. Jolicoeur, H. Rayburn, J. C. Baker, and M. Tessier-Lavigne. 2004. PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. Nature 430:93–98.[CrossRef][Medline]
Lundin, L. G. 1993. Evolution of the vertebrate genome as reflected in paralogous chromosomal regions in man and the house mouse. Genomics 16:1–19.[CrossRef][Web of Science][Medline]
Miller, M. A., and R. E. Steele. 2000. Lemon encodes an unusual receptor protein-tyrosine kinase expressed during gametogenesis in Hydra. Dev. Biol. 224:286–298.[CrossRef][Medline]
Minguillon, C., and J. Garcia-Fernandes. 2003. Genesis and evolution of the Evx and Mox genes and the extended Hox and ParaHox gene clusters. Genome Biol. 4:R12.[Medline]
Mossie, K., B. Jallal, F. Alves, I. Sures, G. D. Plowman, and A. Ullrich. 1995. Colon carcinoma kinase-4 defines a new subclass of the receptor tyrosine kinase family. Oncogene 16:2179–2184.
Muller, W. E., M. Kruse, B. Blumbach, A. Skorokhod, and I. M. Muller. 1999. Gene structure and function of tyrosine kinases in the marine sponge Geodia cydonium: autapomorphic characters in Metazoa. Gene 238:179–193.[CrossRef][Medline]
Ohno, S. 1970. Evolution by gene duplication. Springer-Verlag, New York.
Parichy, D. M., D. G. Ransom, B. Paw, L. I. Zon, and S. L. Johnson. 2000. An orthologue of the kit-related gene fms is required for development of neural crest-derived xanthophores and a subpopulation of adult melanocytes in the zebrafish, Danio rerio. Development 127:3031–3044.[Abstract]
Pebusque, M. J., F. Coulier, D. Birnbaum, and P. Pontarotti. 1998. Ancient large-scale genome duplications: phylogenetic and linkage analyses shed light on chordate genome evolution. Mol. Biol. Evol. 15:1145–1159.[Abstract]
Perez, D. M. 2003. The evolutionarily triumphant G-protein-coupled-receptor. Mol. Pharmacol. 63:1202–1205.
Perrière, G., and M. Gouy. 1996. WWW-query: an on-line retrieval system for biological sequence banks. Biochimie 78:364–369.[Medline]
Plowman, G. D., S. Sudarsanam, J. Bingham, D. Whyte, and T. Hunter. 1999. The protein kinases of Caenorhabditis elegans: a model for signal transduction in multicellular organisms. Proc. Natl. Acad. Sci. USA 96:13603–13610.
Popovici, C., D. Isnardon, D. Birnbaum, and R. Roubin. 2002. Caenorhabditis elegans receptors related to mammalian vascular endothelial growth factor receptors are expressed in neural cells. Neurosci. Lett. 329:116–120.[CrossRef][Medline]
Popovici, C., R. Roubin, F. Coulier, P. Pontarotti, and D. Birnbaum. 1999. The family of Caenorhabditis elegans tyrosine kinase receptors: similarities and differences with mammalian receptors. Genome Res. 9:1026–1039.
Rikke, B. A., S. Murakami, and T. E. Johnson. 2000. Paralogy and orthology of tyrosine kinases that can extend the life span of Caenorhabditis elegans. Mol. Biol. Evol. 17:671–683.
Robinson, D. R., Y. M. Wu, and S. F. Lin. 2000. The protein tyrosine kinase family of the human genome. Oncogene 19:5548–5557.[CrossRef][Web of Science][Medline]
Rousset, D., F. Agnes, P. Lachaume, C. Andre, and F. Galibert. 1995. Molecular evolution of the genes encoding receptor tyrosine kinase with immunoglobulinlike domains. J. Mol. Evol. 41:421–429.[CrossRef][Web of Science][Medline]
Satou, Y., Y. Sasakura, L. Yamada, K. S. Imai, N. Satoh, and B. Degnan. 2003. A genomewide survey of developmentally relevant genes in Ciona intestinalis. V. Genes for receptor tyrosine kinase pathway and notch signaling pathway. Dev. Genes Evol. 213:254–263.[CrossRef][Medline]
Shibuya, M. 2002. Vascular endothelial growth factor receptor family genes: when did the three genes phylogenetically segregate? Biol. Chem. 383:1573–1579.[CrossRef][Web of Science][Medline]
Suga, H., K. Katoh, and T. Miyata. 2001. Sponge homologs of vertebrate protein tyrosine kinases and frequent domain shufflings in the early evolution of animals before the parazoan-eumetazoan split. Gene 280:195–201.[CrossRef][Web of Science][Medline]
Taylor, J. S., and H. Brinkmann. 2001. 2R or not 2R? Trends Genet. 17:488–489.[CrossRef][Medline]
Vicogne, J., J. P. Pin, V. Lardans, M. Capron, C. Noel, and C. Dissous. 2003. An unusual receptor tyrosine kinase of Schistosoma mansoni contains a Venus flytrap module. Mol. Biochem. Parasitol. 126:51–62.[CrossRef][Medline]
Wolfe, K. H. 2001. Yesterday's polyploids and the mystery of diploidization. Nat. Rev. Genet. 2:333–341.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. Braasch, J.-N. Volff, and M. Schartl The Endothelin System: Evolution of Vertebrate-Specific Ligand-Receptor Interactions by Three Rounds of Genome Duplication Mol. Biol. Evol., April 1, 2009; 26(4): 783 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yang, S. Yuzawa, and J. Schlessinger Contacts between membrane proximal regions of the PDGF receptor ectodomain are required for receptor activation but not for receptor dimerization PNAS, June 3, 2008; 105(22): 7681 - 7686. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Mills, R. J. Nuckels, and D. M. Parichy Deconstructing evolution of adult phenotypes: genetic analyses of kit reveal homology and evolutionary novelty during adult pigment pattern development of Danio fishes Development, March 15, 2007; 134(6): 1081 - 1090. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||