Skip to main content

Advertisement

SpringerLink
Log in

Conserved intron positions in FGFR genes reflect the modular structure of FGFR and reveal stepwise addition of domains to an already complex ancestral FGFR

  • Original Article
  • Published:
Development Genes and Evolution Aims and scope Submit manuscript

Abstract

We have analyzed the evolution of fibroblast growth factor receptor (FGFR) tyrosine kinase genes throughout a wide range of animal phyla. No evidence for an FGFR gene was found in Porifera, but we tentatively identified an FGFR gene in the placozoan Trichoplax adhaerens. The gene encodes a protein with three immunoglobulin-like domains, a single-pass transmembrane, and a split tyrosine kinase domain. By superimposing intron positions of 20 FGFR genes from Placozoa, Cnidaria, Protostomia, and Deuterostomia over the respective protein domain structure, we identified ten ancestral introns and three conserved intron groups. Our analysis shows (1) that the position of ancestral introns correlates to the modular structure of FGFRs, (2) that the acidic domain very likely evolved in the last common ancestor of triploblasts, (3) that splicing of IgIII was enabled by a triploblast-specific insertion, and (4) that IgI is subject to substantial loss or duplication particularly in quickly evolving genomes. Moreover, intron positions in the catalytic domain of FGFRs map to the borders of protein subdomains highly conserved in other serine/threonine kinases. Nevertheless, these introns were introduced in metazoan receptor tyrosine kinases exclusively. Our data support the view that protein evolution dating back to the Cambrian explosion took place in such a short time window that only subtle changes in the domain structure are detectable in extant representatives of animal phyla. We propose that the first multidomain FGFR originated in the last common ancestor of Placozoa, Cnidaria, and Bilateria. Additional domains were introduced mainly in the ancestor of triploblasts and in the Ecdysozoa.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Beermann A, Schröder R (2008) Sites of Fgf signalling and perception during embryogenesis of the beetle Tribolium castaneum. Dev Genes Evol 218:153–167

    Article  CAS  PubMed  Google Scholar 

  • Bourlat SJ, Nielsen C, Economou AD, Telford MJ (2008) Testing the new animal phylogeny: a phylum level molecular analysis of the animal kingdom. Mol Phylogenet Evol 49:23–31

    Article  CAS  PubMed  Google Scholar 

  • Bridge D, Cunningham CW, DeSalle R, Buss LW (1995) Class-level relationship in the phylum Cnidaria: molecular and morphological evidence. Mol Biol Evol 12:679–9

    CAS  PubMed  Google Scholar 

  • Coulier F, Pontarotti P, Roubin R, Hartung H, Goldfarb M, Birnbaum D (1997) Of worms and men: an evolutionary perspective on the fibroblast growth factor (FGF) and FGF receptor families. J Mol Evol 44:43–56

    Article  CAS  PubMed  Google Scholar 

  • D’Aniello S, Iirimia M, Maeso I, Pascual-Anaya J, Jiménez-Delgado S, Bertrand S, Garcia-Fernàndez J (2008) Gene expansion and retention leads to a diverse tyrosine kinase superfamily in Amphioxus. Mol Biol Evol 25:1841–1854

    Article  PubMed  CAS  Google Scholar 

  • Dehal P, Satou Y, Campbell RK, Chapman J, Degnan B, De Tomaso A, Davidson B, Di Gregorio A, Gelpke M, Goodstein DM, Harafuji N, Hastings KE, Ho I, Hotta K, Huang W, Kawashima T, Lemaire P, Martinez D, Meinertzhagen IA, Necula S, Nonaka M, Putnam N, Rash S, Saiga H, Satake M, Terry A, Yamada L, Wang HG, Awazu S, Azumi K, Boore J, Branno M, Chin-Bow S, DeSantis R, Doyle S, Francino P, Keys DN, Haga S, Hayashi H, Hino K, Imai KS, Inaba K, Kano S, Kobayashi K, Kobayashi M, Lee BI, Makabe KW, Manohar C, Matassi G, Medina M, Mochizuki Y, Mount S, Morishita T, Miura S, Nakayama A, Nishizaka S, Nomoto H, Ohta F, Oishi K, Rigoutsos I, Sano M, Sasaki A, Sasakura Y, Shoguchi E, Shin-i T, Spagnuolo A, Stainier D, Suzuki MM, Tassy O, Takatori N, Tokuoka M, Yagi K, Yoshizaki F, Wada S, Zhang C, Hyatt PD, Larimer F, Detter C, Doggett N, Glavina T, Hawkins T, Richardson P, Lucas S, Kohara Y, Levine M, Satoh N, Rokhsar DS (2002) The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. Science 298(5601):2157–2167

    Google Scholar 

  • Freeman RM Jr, Wu M, Cordonnier-Pratt MM, Pratt LH, Gruber CE, Smith M, Lander ES, Stange-Thomann N, Lowe CJ, Gerhart J, Kirschner M (2008) cDNA sequences for transcription factors and signaling proteins of the hemichordate Saccoglossus kowalevskii: efficacy of the expressed sequence tag (EST) approach for evolutionary and developmental studies of a new organism. Biol Bull 14:284–302

    Article  Google Scholar 

  • Furdui CM, Lew ED, Schlessinger J, Anderson KS (2006) Autophosphorylation of FGFR1 kinase is mediated by a sequential and precisely ordered reaction. Mol Cell 21:711–717

    Article  CAS  PubMed  Google Scholar 

  • Gilbert W (1978) Why genes in pieces? Nature 271:501

    Article  CAS  PubMed  Google Scholar 

  • Gisselbrecht S, Skeath JB, Doe CQ, Michelson AM (1996) heartless encodes a fibroblast growth factor receptor (DFR1/DFGF-R2) involved in the directional migration of early mesodermal cells in the Drosophila embryo. Genes Dev 10:3003–3017

    Article  CAS  PubMed  Google Scholar 

  • Grassot J, Gouy M, Perriere G, Mouchiroud G (2006) Origin and molecular evolution of receptor tyrosine kinases with immunoglobulin-like domains. Mol Biol Evol 23:1232–1241

    Article  CAS  PubMed  Google Scholar 

  • Hanks SK, Hunter T (1995) The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J 9:576–596

    CAS  PubMed  Google Scholar 

  • Hanks SK, Quinn AM, Hunter T (1988) The protein kinase family: conserved features and deduced phylogeny of the catalytic domain. Science 241:42–52

    Article  CAS  PubMed  Google Scholar 

  • Hassel M, Albert K, Hofheinz S (1993) Pattern formation in Hydra vulgaris is controlled by lithium sensitive processes. Dev Biol 156:362–371

    Article  CAS  PubMed  Google Scholar 

  • Hemmrich G, Anokhin B, Zacharias H, Bosch TC (2007) Molecular phylogenetics in Hydra, a classical model in evolutionary developmental biology. Mol Phylogenetics Evol 44:281–290

    Article  CAS  Google Scholar 

  • Holstein TW, Campbell RD, Tardent P (1990) Identity crisis. Nature 346:21–22

    Article  Google Scholar 

  • Huang P, Stern MJ (2005) FGF signaling in flies and worms: More and more relevant to vertebrate biology. Cytokine Growth Factor Rev 16:151–158

    Google Scholar 

  • Imai KS, Hino K, Yagi K, Satoh N, Satou Y (2004) Gene expression profiles of transcription factors and signalling molecules in the ascidian embryo: towards a comprehensive understanding of gene networks. Development 131(16):4047–4058

    Article  CAS  PubMed  Google Scholar 

  • Kadam S, McMahon A, Tzou P, Stathopoulos A (2009) FGF ligands in Drosophila have distinct activities required to support cell migration and differentiation. Development 136:739–747

    Article  CAS  PubMed  Google Scholar 

  • Kawashima T, Lemaire P, Martinez D, Meinertzhagen IA, Necula S, Nonaka M, Putnam N, Rash S, Saiga H, Satake M, Terry A, Yamada L, Wang HG, Awazu S, Azumi K, Boore J, Branno M, Chin-Bow S, DeSantis R, Doyle S, Francino P, Keys DN, Haga S, Hayashi H, Hino K, Imai KS, Inaba K, Kano S, Kobayashi K, Kobayashi M, Lee BI, Makabe KW, Manohar C, Matassi G, Medina M, Mochizuki Y, Mount S, Morishita T, Miura S, Nakayama A, Nishizaka S, Nomoto H, Ohta F, Oishi K, Rigoutsos I, Sano M, Sasaki A, Sasakura Y, Shoguchi E, Shin-i T, Spagnuolo A, Stainier D, Suzuki MM, Tassy O, Takatori N, Tokuoka M, Yagi K, Yoshizaki F, Wada S, Zhang C, Hyatt PD, Larimer F, Detter C, Doggett N, Glavina T, Hawkins T, Richardson P, Lucas S, Kohara Y, Levine M, Satoh N, Rokhsar DS (2002) The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. Science 298(5601):2157–2167

    Article  PubMed  CAS  Google Scholar 

  • King N, Carroll SB (2001) A receptor tyrosine kinase from choanoflagellates: molecular insights into early animal evolution. Proc Natl Acad Sci U S A 98(26):15032–15037

    Article  CAS  PubMed  Google Scholar 

  • King N, Westbrook MJ, Young SL, Kuo A, Abedin M, Chapman J, Fairclough S, Hellsetn U, Isogai Y, Letunic I, Man M, Pincus D, Putnam N, Rokas A, Wright KJ, Zuzow R, Dirks W, Good M, Goodstein D, Lemons D, Li W, Lyons JB, Morris A, Nicols S, Richter DJ, Salamov A, Sequencing JGI, Bork P, Lim WA, Manning G, Miller WT, McGinnis W, Shapiro H, Tijan R, Grigoriev IV, Rokhsar D (2008) The genome opf the choanoflagellate Monosiga brevicollis and the origin of metazoans. Nature 451(7180):783–788

    Article  CAS  PubMed  Google Scholar 

  • Kiselyov VV, Li S, Berezin V, Bock E (2009) Insight into the structural mechanism of the bi-modal action of an NCAM mimetic, the C3 peptide. Neurosci Lett 452:224–227

    Article  CAS  PubMed  Google Scholar 

  • Klämbt C, Glazer L, Shilo BZ (1992) breathless, a Drosophila FGF receptor homolog, is essential for migration of tracheal and specific midline glial cells. Genes Dev 6:1668–1678

    Article  PubMed  Google Scholar 

  • Klingseisen A, Clark I, Gryzik MHA (2009) Differential and overlapping functions of two closely related Drosophila FGF8-like growth factors in mesoderm development. Development 136:2393–2402

    Article  CAS  PubMed  Google Scholar 

  • Kwiatkowski BA, Kirillova I, Richard RE, Israeli D, Yablonka-Reuveni Z (2008) FGFR4 and its novel splice form in myogenic cells: interplay of glycosylation and tyrosine phosphorylation. J Cell Physiol 215:803–817

    Article  CAS  PubMed  Google Scholar 

  • Leys SP, Rokhsar DS, Degnan BM (2005) Sponges. Curr Biol 15(4):R114–R115

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Basilico C, Mansukhani A (1994) Cell transformation by fibroblast growth factors can be suppressed by truncated fibroblast growth factor receptors. Mol Cell Biol 14(11):7660–7669

    CAS  PubMed  Google Scholar 

  • Liu M, Grigoriev A (2004) Protein domains correlate strongly with exons in multiple eukaryotic genomes—evidence of exon shuffling? Trends Genet 20:399–403

    Article  PubMed  CAS  Google Scholar 

  • Logsdon JM (2004) Worm genomes hold the smoking guns of intron gain. Proc Natl Acad Sci U S A 101:11195–11196

    Article  CAS  PubMed  Google Scholar 

  • Martin VJ, Littlefield CL, Archer WE, Bode HR (1997) Embryogenesis in Hydra. Biol Bull 192:345–363

    Article  CAS  PubMed  Google Scholar 

  • Matus DQ, Thomsen GH, Martindale MQ (2007) FGF signaling in gastrulation and neuronal development in Nematostella vectensis, an anthozoan cnidarian. Dev Genes Evol 217:137–148

    Article  CAS  PubMed  Google Scholar 

  • Mistry N, Harrington W, Lasda E, Wagner EJ, Garcia-Blanco MA (2003) Of urchins and men: evolution of an alternative splicing unit in fibroblast growth factor receptor genes. RNA 9:209–217

    Article  CAS  PubMed  Google Scholar 

  • Mohammadi M, Olsen SK, Ibrahimi OA (2005) Structural basis for fibroblast growth factor receptor activation. Cytokine Growth Factor Rev 16:107–137

    Article  CAS  PubMed  Google Scholar 

  • Nagendra HG, Harrington AE, Harmer NJ, Pellegrini L, Blundell TL, Burke DF (2001) Sequence analyses and comparative modelling of fly and worm fibroblast growth factor receptors indicate that the determinants for FGF and heparin binding are retained in evolution. FEBS Lett 501:51–58

    Article  CAS  PubMed  Google Scholar 

  • Neilson KM, Friesel R (1996) Ligand-independent activation of fibroblast growth factor receptors by point mutations in the extracellular, transmembrane and kinase domains. J Biol Chem 271(40):25049–25057

    Article  CAS  PubMed  Google Scholar 

  • Ogawa K, Kobayashi C, Hayashi T, Orii H, Watanabe K, Agata K (2002) Planarian fibroblast growth factor receptor homologs expressed in stem cells and cephalic ganglions. Dev Growth Differ 44:191–204

    Article  CAS  PubMed  Google Scholar 

  • Olsen SK, Ibrahimi OA, Raucci A, Zhang F, Eliseenkova AV, Yayon A, Basilico C, Linhardt RJ, Schlessinger J, Mohammadi M (2004) Insight into the molecular basis of fibroblast growth factor receptor autoinhibition and ligand binding promiscuity. Proc Natl Acad Sci 101:935–940

    Article  CAS  PubMed  Google Scholar 

  • Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M (1996) Receptor specificity of the fibroblast growth factor family. J Biol Chem 271:15292–15297

    Article  CAS  PubMed  Google Scholar 

  • Philippe H, Derelle R, Lopez P, Pick K, Borchiellini C, Boury-Esnault N, Vacelet J, Renard E, Houliston E, Quéinnec E, Da Silva C, Wincker P, Le Guyader H, Leys S, Jackson DJ, Schreiber F, Erpenbeck D, Morgenstern B, Wörheide G, Manuel M (2009) Phylogenomics revives traditional views on deep animal relationships. Curr Biol 19:R339–R341

    Article  CAS  Google Scholar 

  • Putnam NH, Srivastava M, Hellsten U, Dirks B, Chapman J, Salamov A, Terry A, Shapiro H, Lindquist E, Kapitonov VV, Jurka J, Genikhovich G, Grigoriev IV, Lucas SM, Steele RE, Finnerty JR, Technau U, Martindale MQ, Rokhsar DS (2007) Sea anemone genome reveals ancestral eumetazoan gene repertoire and genomic organization. Science 317:86–94

    Article  CAS  PubMed  Google Scholar 

  • Raible F, Tessmar-Raible K, Osoegawa K, Wincker P, Jubin C, Balavoine G, Ferrier D, Benes V, de Jong P, Weissenbach J, Bork P, Arendt D (2005) Vertebrate-type intron-rich genes in the marine annelid Platynereis dumerilii. Science 310:1325–1326

    Article  CAS  PubMed  Google Scholar 

  • Rentzsch F, Fritzenwanker JH, Scholz CB, Technau U (2008) FGF signalling controls formation of the apical sensory organ in the cnidarian Nematostella vectensis. Development 135:1761–1769

    Article  CAS  PubMed  Google Scholar 

  • Resch A, Xing Y, Alekseyenko A, Modrek B, Lee C (2004) Evidence for a subpopulation of conserved alternative splicing events under selection pressure for protein reading frame preservation. Nucleic Acids Res 32:1261–1269

    Article  CAS  PubMed  Google Scholar 

  • Rokas A, Kruger D, Carroll SB (2005) Animal evolution and the molecular signature of radiation compressed in time. Science 310:1933–1938

    Article  PubMed  Google Scholar 

  • Roy SW, Irimia M (2009) Splicing in the eukaryotic ancestor: form, function and dysfunction. Trends Ecol Evol 28(8):447–455

    Article  Google Scholar 

  • Sanchez-Heras E, Howell FV, Williams G, Doherty P (2006) The fibroblast growth factor receptor acidic box is essential for interactions with N-cadherin and all of the major isoforms of neural cell adhesion molecule. J Biol Chem 281:35208–35216

    Article  CAS  PubMed  Google Scholar 

  • Satou Y, Mineta K, Ogasawara M, Sasakura Y, Shoguchi E, Keisuke U, Yamada L, Matsumoto J, Wasserscheid J, Dewar K, Wiley GB, Macmil SL, Roe BA, Zeller RW, Hastings KEM, Lemaire P, Lindquist E, Endo T, Hotta K, Inaba K (2008) Improved genome assembly and evidence-based global gene model set for the chordate Ciona intestinalis: new insight into the intron and operon populations. Genome Biology 9(10):R152

    Article  PubMed  CAS  Google Scholar 

  • Schierwater B, Eitel M, Jakob W, Osigus HJ, Hadrys H, Dellaporta SL, Kolokotronis SO, Desalle R (2009) Concatenated analysis sheds light on early metazoan evolution and fuels a modern “Urmetazoon” hypothesis. PLoS Biol 7:e20

    Article  PubMed  CAS  Google Scholar 

  • Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103:211–225

    Article  CAS  PubMed  Google Scholar 

  • Schmidt EE, Davies CJ (2007) The origins of polypeptide domains. Bioessays 29:262–270

    Article  CAS  PubMed  Google Scholar 

  • Schröder R, Beermann A, Wittkopp N, Lutz R (2008) From development to biodiversity—Tribolium castaneum, an insect model organism for short germ band development. Dev Genes Evol 218:119–126

    Article  PubMed  Google Scholar 

  • Shimizu A, Tada K, Shukunami C, Shimizu A, Tada K, Shukunami C (2001) A novel alternatively spliced fibroblast growth factor receptor 3 isoform lacking the acid box domain is expressed during chondrogenic differentiation of ATDC5 cells. J Biol Chem 276:11031–11040

    Article  CAS  PubMed  Google Scholar 

  • Srivastava M, Begovic E, Chapman J, Putnam NH, Hellsten U, Kawashima T, Kuo A, Mitros T, Salamov A, Carpenter ML, Signorovitch AY, Moreno MA, Kamm K, Grimwood J, Schmutz J, Shapiro H, Grigoriev IV, Buss LW, Schierwater B, Dellaporta SL, Rokhsar DS (2008) The Trichoplax genome and the nature of placozoans. Nature 454(7207):955–960

    Article  CAS  PubMed  Google Scholar 

  • Steinberg SF (2008) Structural basis of protein kinase C isoform function. Physiol Rev 88:1341–1378

    Article  CAS  PubMed  Google Scholar 

  • Sudhop S, Coulier F, Bieller A, Vogt A, Hotz T, Hassel M (2004) Signaling by the FGFR-like tyrosine kinase, Kringelchen, is essential for bud detachment in Hydra vulgaris. Development 131:4001–4011

    Article  CAS  PubMed  Google Scholar 

  • Sullivan JC, Finnerty JR (2007) A surprising abundance of human disease genes in a simple “basal” animal, the starlet sea anemone (Nematostella vectensis). Genome 50:689–692

    Article  PubMed  Google Scholar 

  • Sullivan JC, Reitzel AM, Finnerty JR (2006) A high percentage of introns in human genes were present early in animal evolution: evidence from the basal metazoan Nematostella vectensis. Genome Inform 17:219–229

    CAS  PubMed  Google Scholar 

  • Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599

    Article  CAS  PubMed  Google Scholar 

  • Technau U, Rudd S, Maxwell P, Gordon PM, Saina M, Grasso LC, Hayward DC, Sensen CW, Saint R, Holstein TW, Ball EE, Miller DJ (2005) Maintenance of ancestral complexity and non-metazoan genes in two basal cnidarians. Trends Genet 21:633–639

    Article  CAS  PubMed  Google Scholar 

  • Thisse B, Thisse C (2005) Functions and regulations of fibroblast growth factor signaling during embryonic development. Dev Biol 287:390–402

    Article  CAS  PubMed  Google Scholar 

  • Tribolium Genome Sequencing Consortium (2008) The genome of the model beetle and pest Tribolium castaneum. Nature 452:949–955

    Article  CAS  Google Scholar 

  • Wang LJS, Li Y, Paradesi MS, Brown SJ (2007) BeetleBase: the model organism database for Tribolium castaneum. Nucleic Acid Res 35:D476–D479 database issue

    Article  CAS  PubMed  Google Scholar 

  • Wheelan SJ, Church DM, Ostell JM. (2001) Spidey: a tool for mRNA-to-genomic alignments. Genome Res. 11(11):1952–1957

    Google Scholar 

Download references

Acknowledgements

We thank Gabriele Petersen for critical reading of the manuscript and Torsten Rentrop for help with the initial bioinformatic work on the Hydra FGFR gene. We are indebted to Dan Rokhsar and Jarrod Chapman, JGI, for generous access to the unpublished Hydra genome project. We thank the Acorn Worm Genome Sequencing Consortium and the Capitella community for making their data available, which were produced by the US Department of Energy Joint Genome Institute http://www.jgi.doe.gov/ in collaboration with the user community, and the BCM-HGSC for providing the scaffold covering the FGFRs. Anke Beermann and Reinhardt Schröder kindly provided unpublished information concerning Tribolium FGFR. Last but not least, we thank Katja Gessner, our skillful secretary wizardess.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. FB 17, Morphology and Evolution of Invertebrates, Philipps Universitaet Marburg, Karl von Frisch Str. 8, 35032, Marburg, Germany

    Nicole Rebscher, Christina Deichmann, Stefanie Sudhop & Monika Hassel

  2. Dept. of Organismal Biology and Anatomy, The University of Chicago, 1027 East 57th Street, 60637-1508, Chicago, IL, USA

    Stefanie Sudhop, Jens Holger Fritzenwanker & Stephen Green

Authors
  1. Nicole Rebscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christina Deichmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefanie Sudhop
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jens Holger Fritzenwanker
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stephen Green
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Monika Hassel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Monika Hassel.

Additional information

Communicated by D.A. Weisblat

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplement 1

Alignment of all used FGFRs and their intron positions superimposed to the protein sequence and domain annotation (PPT 231 kb)

Supplement 2

Assembled and annotated sequences from Trichoplax, Hydra, Nematostella, Lottia Capitella, Tribolium, and Saccoglossus used in the present study (DOC 880 kb)

Supplement 3

Intron size of the three cnidarian FGFRs in comparison to FGFR1 (human) (DOC 61 kb)

Supplement 4

Matrix representation of constitutively spliced introns in FGFR genes across the animal kingdom (DOC 97 kb)

Supplement 5

Intron positions in the highly conserved kinase domains of metazoan receptor tyrosine kinases are not related to intron positions in the choanoflagellate RTK nor in the serine–threonine kinase, PKC (PPT 139 kb)

Supplement 6

Evolutionary relationships of 27 kinases used in this study (PPT 90 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rebscher, N., Deichmann, C., Sudhop, S. et al. Conserved intron positions in FGFR genes reflect the modular structure of FGFR and reveal stepwise addition of domains to an already complex ancestral FGFR. Dev Genes Evol 219, 455–468 (2009). https://doi.org/10.1007/s00427-009-0309-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00427-009-0309-5

Keywords

Search

Navigation