Abstract
The Ras superfamily of small GTPases illustrates a large functional diversification in the context of a preserved structural framework and a prototypic GTP-binding site. The Ras superfamily of small GTP-binding proteins is essential to regulate the cellular organization and signaling in cells. Members of this superfamily contain a structurally and mechanistically preserved GTP-binding core, with considerable functional and sequence divergence. In this chapter we review the evolutionary structure of the superfamily at the organism and sequence level, presenting a representative tree that reflects the history of the Ras superfamily including crucial evolutionary time points and detailed trees for the Rho, Ras, Rab, Arf, and Ran families. Based on this information we discuss some of the complex relationships between the evolution of proteins and the acquisition of distinctive cellular functions.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Altenhoff AM, Studer RA, Robinson-Rechavi M, Dessimoz C (2012) Resolving the ortholog conjecture: orthologs tend to be weakly, but significantly, more similar in function than paralogs. PLoS Comput Biol 8(5):e1002514. doi:10.1371/journal.pcbi.1002514, PCOMPBIOL-D-11-01584 [pii]
Aspenstrom P, Ruusala A, Pacholsky D (2007) Taking Rho GTPases to the next level: the cellular functions of atypical Rho GTPases. Exp Cell Res 313(17):3673–3679. doi:10.1016/j.yexcr.2007.07.022, S0014-4827(07)00358-8 [pii]
Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, Wrana JL (2005) High-throughput mapping of a dynamic signaling network in mammalian cells. Science 307(5715):1621–1625. doi:10.1126/science.1105776, 307/5715/1621 [pii]
Boureux A, Vignal E, Faure S, Fort P (2007) Evolution of the Rho family of ras-like GTPases in eukaryotes. Mol Biol Evol 24(1):203–216. doi:10.1093/molbev/msl145, msl145 [pii]
Bucci C, Chiariello M (2006) Signal transduction gRABs attention. Cell Signal 18(1):1–8. doi:10.1016/j.cellsig.2005.07.001, S0898-6568(05)00162-2 [pii]
Buchsbaum RJ (2007) Rho activation at a glance. J Cell Sci 120(Pt 7):1149–1152. doi:10.1242/jcs.03428, 120/7/1149 [pii]
Chardin P (2006) Function and regulation of Rnd proteins. Nat Rev Mol Cell Biol 7(1):54–62. doi:10.1038/nrm1788, nrm1788 [pii]
Correll RN, Pang C, Niedowicz DM, Finlin BS, Andres DA (2008) The RGK family of GTP-binding proteins: regulators of voltage-dependent calcium channels and cytoskeleton remodeling. Cell Signal 20(2):292–300. doi:10.1016/j.cellsig.2007.10.028
Dong N, Zhu Y, Lu Q, Hu L, Zheng Y, Shao F (2012) Structurally distinct bacterial TBC-like GAPs link Arf GTPase to Rab1 inactivation to counteract host defenses. Cell 150(5):1029–1041. doi:10.1016/j.cell.2012.06.050
Elam C, Hesson L, Vos MD, Eckfeld K, Ellis CA, Bell A, Krex D, Birrer MJ, Latif F, Clark GJ (2005) RRP22 is a farnesylated, nucleolar, Ras-related protein with tumor suppressor potential. Cancer Res 65(8):3117–3125. doi:10.1158/0008-5472.CAN-04-0749, 65/8/3117 [pii]
Ellis CA, Vos MD, Howell H, Vallecorsa T, Fults DW, Clark GJ (2002) Rig is a novel Ras-related protein and potential neural tumor suppressor. Proc Natl Acad Sci USA 99(15):9876–9881. doi:10.1073/pnas.142193799, 142193799 [pii]
Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, Epstein CB, Zhang X, Wang L, Issner R, Coyne M, Ku M, Durham T, Kellis M, Bernstein BE (2011) Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473(7345):43–49. doi:10.1038/nature09906, nature09906 [pii]
Errico F, Santini E, Migliarini S, Borgkvist A, Centonze D, Nasti V, Carta M, De Chiara V, Prosperetti C, Spano D, Herve D, Pasqualetti M, Di Lauro R, Fisone G, Usiello A (2008) The GTP-binding protein Rhes modulates dopamine signalling in striatal medium spiny neurons. Mol Cell Neurosci 37(2):335–345. doi:10.1016/j.mcn.2007.10.007, S1044-7431(07)00251-5 [pii]
Espinosa EJ, Calero M, Sridevi K, Pfeffer SR (2009) RhoBTB3: a Rho GTPase-family ATPase required for endosome to Golgi transport. Cell 137(5):938–948. doi:10.1016/j.cell.2009.03.043
Freeman JL, Abo A, Lambeth JD (1996) Rac “insert region” is a novel effector region that is implicated in the activation of NADPH oxidase, but not PAK65. J Biol Chem 271(33):19794–19801
Heasman SJ, Ridley AJ (2008) Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol 9(9):690–701. doi:10.1038/nrm2476, nrm2476 [pii]
Hedges SB, Kumar S (2004) Precision of molecular time estimates. Trends Genet 20(5):242–247. doi:10.1016/j.tig.2004.03.004, S0168952504000721 [pii]
Holder M, Lewis PO (2003) Phylogeny estimation: traditional and Bayesian approaches. Nat Rev Genet 4(4):275–284. doi:10.1038/nrg1044, nrg1044 [pii]
Hughes AL, Friedman R (2005) Loss of ancestral genes in the genomic evolution of Ciona intestinalis. Evol Dev 7(3):196–200. doi:10.1111/j.1525-142X.2005.05022.x, EDE05022 [pii]
Ihara K, Muraguchi S, Kato M, Shimizu T, Shirakawa M, Kuroda S, Kaibuchi K, Hakoshima T (1998) Crystal structure of human RhoA in a dominantly active form complexed with a GTP analogue. J Biol Chem 273(16):9656–9666
Ismail SA, Chen YX, Rusinova A, Chandra A, Bierbaum M, Gremer L, Triola G, Waldmann H, Bastiaens PI, Wittinghofer A (2011) Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo. Nat Chem Biol 7(12):942–949. doi:10.1038/nchembio.686
Ismail SA, Chen YX, Miertzschke M, Vetter IR, Koerner C, Wittinghofer A (2012) Structural basis for Arl3-specific release of myristoylated ciliary cargo from UNC119. EMBO J 31(20):4085–4094. doi:10.1038/emboj.2012.257
Jaffe AB, Hall A (2005) Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21:247–269. doi:10.1146/annurev.cellbio.21.020604.150721
Jiang SY, Ramachandran S (2006) Comparative and evolutionary analysis of genes encoding small GTPases and their activating proteins in eukaryotic genomes. Physiol Genomics 24(3):235–251. doi:10.1152/physiolgenomics.00210.2005, 00210.2005 [pii]
Kahn RA, Cherfils J, Elias M, Lovering RC, Munro S, Schurmann A (2006) Nomenclature for the human Arf family of GTP-binding proteins: ARF, ARL, and SAR proteins. J Cell Biol 172(5):645–650. doi:10.1083/jcb.200512057, jcb.200512057 [pii]
Karnoub AE, Weinberg RA (2008) Ras oncogenes: split personalities. Nat Rev Mol Cell Biol 9(7):517–531. doi:10.1038/nrm2438
Kemena C, Notredame C (2009) Upcoming challenges for multiple sequence alignment methods in the high-throughput era. Bioinformatics 25(19):2455–2465. doi:10.1093/bioinformatics/btp452
Klopper TH, Kienle N, Fasshauer D, Munro S (2012) Untangling the evolution of Rab G proteins: implications of a comprehensive genomic analysis. BMC Biol 10:71. doi:10.1186/1741-7007-10-71
Kondrashov FA, Rogozin IB, Wolf YI, Koonin EV (2002) Selection in the evolution of gene duplications. Genome Biol 3(2):RESEARCH0008
Krengel U (1999) Struktur und guanosintriphosphat-hydrolysemechanismus des C-terminal verkuerzten menschlichen krebsproteins P21-H-RAS. Germany
Lartillot N, Brinkmann H, Philippe H (2007) Suppression of long-branch attraction artefacts in the animal phylogeny using a site-heterogeneous model. BMC Evol Biol 7(Suppl 1):S4. doi:10.1186/1471-2148-7-S1-S4, 1471-2148-7-S1-S4 [pii]
Li Y, Kelly WG, Logsdon JM Jr, Schurko AM, Harfe BD, Hill-Harfe KL, Kahn RA (2004) Functional genomic analysis of the ADP-ribosylation factor family of GTPases: phylogeny among diverse eukaryotes and function in C. elegans. FASEB J 18(15):1834–1850. doi:10.1096/fj.04-2273com, 18/15/1834 [pii]
Mackiewicz P, Wyroba E (2009) Phylogeny and evolution of Rab7 and Rab9 proteins. BMC Evol Biol 9:101. doi:10.1186/1471-2148-9-101, 1471-2148-9-101 [pii]
Mulloy JC, Cancelas JA, Filippi MD, Kalfa TA, Guo F, Zheng Y (2010) Rho GTPases in hematopoiesis and hemopathies. Blood 115(5):936–947. doi:10.1182/blood-2009-09-198127, blood-2009-09-198127 [pii]
Munro S (2005) The Arf-like GTPase Arl1 and its role in membrane traffic. Biochem Soc Trans 33(Pt 4):601–605. doi:10.1042/BST0330601, BST0330601 [pii]
Ostlund G, Schmitt T, Forslund K, Kostler T, Messina DN, Roopra S, Frings O, Sonnhammer EL (2010) InParanoid 7: new algorithms and tools for eukaryotic orthology analysis. Nucleic Acids Res 38(Database issue):D196–D203. doi:10.1093/nar/gkp931, gkp931 [pii]
Park HO, Bi E (2007) Central roles of small GTPases in the development of cell polarity in yeast and beyond. Microbiol Mol Biol Rev 71(1):48–96. doi:10.1128/MMBR.00028-06, 71/1/48 [pii]
Pereira-Leal JB, Seabra MC (2001) Evolution of the Rab family of small GTP-binding proteins. J Mol Biol 313(4):889–901. doi:10.1006/jmbi.2001.5072, S0022-2836(01)95072-7 [pii]
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(5834):86–94. doi:10.1126/science.1139158, 317/5834/86 [pii]
Raaijmakers JH, Bos JL (2009) Specificity in Ras and Rap signaling. J Biol Chem 284(17):10995–10999. doi:10.1074/jbc.R800061200
Renault L, Kuhlmann J, Henkel A, Wittinghofer A (2001) Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1). Cell 105(2):245–255
Rojas AM, Fuentes G, Rausell A, Valencia A (2012) Evolution: The Ras protein superfamily: Evolutionary tree and role of conserved amino acids. J Cell Biol 196(2):189–201. doi:10.1083/jcb.201103008, jcb.201103008 [pii]
Ronquist F, Huelsenbeck JP (2003) MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19(12):1572–1574
Saito-Nakano Y, Mitra BN, Nakada-Tsukui K, Sato D, Nozaki T (2007) Two Rab7 isotypes, EhRab7A and EhRab7B, play distinct roles in biogenesis of lysosomes and phagosomes in the enteric protozoan parasite Entamoeba histolytica. Cell Microbiol 9(7):1796–1808. doi:10.1111/j.1462-5822.2007.00915.x, CMI915 [pii]
Schlessinger K, Hall A, Tolwinski N (2009) Wnt signaling pathways meet Rho GTPases. Genes Dev 23(3):265–277. doi:10.1101/gad.1760809, 23/3/265 [pii]
Schwartz SL, Cao C, Pylypenko O, Rak A, Wandinger-Ness A (2007) Rab GTPases at a glance. J Cell Sci 120(Pt 22):3905–3910. doi:10.1242/jcs.015909, 120/22/3905 [pii]
Seo HC, Kube M, Edvardsen RB, Jensen MF, Beck A, Spriet E, Gorsky G, Thompson EM, Lehrach H, Reinhardt R, Chourrout D (2001) Miniature genome in the marine chordate Oikopleura dioica. Science 294(5551):2506. doi:10.1126/science.294.5551.2506, 294/5551/2506 [pii]
Shi GX, Andres DA (2005) Rit contributes to nerve growth factor-induced neuronal differentiation via activation of B-Raf-extracellular signal-regulated kinase and p38 mitogen-activated protein kinase cascades. Mol Cell Biol 25(2):830–846. doi:10.1128/MCB.25.2.830-846.2005, 25/2/830 [pii]
Shi GX, Cai W, Andres DA (2013) Rit subfamily small GTPases: regulators in neuronal differentiation and survival. Cell Signal 25(10):2060–2068. doi:10.1016/j.cellsig.2013.06.002
Stenmark H (2009) Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol 10(8):513–525. doi:10.1038/nrm2728, nrm2728 [pii]
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(12):633–639. doi:10.1016/j.tig.2005.09.007, S0168-9525(05)00287-8 [pii]
Valencia A, Kjeldgaard M, Pai EF, Sander C (1991) GTPase domains of ras p21 oncogene protein and elongation factor Tu: analysis of three-dimensional structures, sequence families, and functional sites. Proc Natl Acad Sci USA 88(12):5443–5447
Venancio TM, Balaji S, Iyer LM, Aravind L (2009) Reconstructing the ubiquitin network: cross-talk with other systems and identification of novel functions. Genome Biol 10(3):R33. doi:10.1186/gb-2009-10-3-r33, gb-2009-10-3-r33 [pii]
Wennerberg K, Rossman KL, Der CJ (2005) The Ras superfamily at a glance. J Cell Sci 118(5):843–846. doi:10.1242/jcs.01660
Yang Z (2002) Small GTPases: versatile signaling switches in plants. Plant Cell 14(Suppl):S375–S388
Yang S, Bourne PE (2009) The evolutionary history of protein domains viewed by species phylogeny. PLoS One 4(12):e8378. doi:10.1371/journal.pone.0008378
Zerial M, McBride H (2001) Rab proteins as membrane organizers. Nat Rev Mol Cell Biol 2(2):107–117. doi:10.1038/35052055
Zmasek CM, Godzik A (2011) Strong functional patterns in the evolution of eukaryotic genomes revealed by the reconstruction of ancestral protein domain repertoires. Genome Biol 12(1):R4. doi:10.1186/gb-2011-12-1-r4, gb-2011-12-1-r4 [pii]
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Wien
About this chapter
Cite this chapter
Rojas, A.M., Valencia, A. (2014). Evolution of the Ras Superfamily of GTPases. In: Wittinghofer, A. (eds) Ras Superfamily Small G Proteins: Biology and Mechanisms 1. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1806-1_1
Download citation
DOI: https://doi.org/10.1007/978-3-7091-1806-1_1
Published:
Publisher Name: Springer, Vienna
Print ISBN: 978-3-7091-1805-4
Online ISBN: 978-3-7091-1806-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)