Skip to main content
SpringerLink
Log in
Book cover

Neurofibromatosis Type 1 pp 253–268Cite as

Insights into NF1 from Evolution

  • Chapter
  • First Online:

  • 1546 Accesses

Abstract

The gene product of NF1, neurofibromin, is a very large protein. The known functional domains (GRD, Sec14 and PH-like domain) account for only about 20 % of the size. Comparison of human neurofibromin with its homologues from various species led to the detection of the presently known domains and maybe will also help to identify further functional regions of this protein. Evolutionary comparisons also revealed that NF1 is a very old gene with its origin in the fungi/metazoa ancestor, which is approximately 1,200 million years old. A strong evolutionary constraint has to lie on neurofibromin function as the gene structure and exon organisation are conserved even between human and ray-finned fish (Takifugu rupripes) and almost no change is observed in primate evolution. In addition to the coding sequence also, the NF1 genomic region exhibits very little change during primate evolution. In contrast, the region of the three genes inserted in an NF1 intron, OMG, EVI2A and EVI2B, seems to be more variable.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Assum G, Schmegner C (2008) NF1 gene in evolution. In: Kaufmann D (ed) Neurofibromatoses, vol 16, Monographs in human genetics. Karger, Basel, pp 103–112

    Chapter  Google Scholar 

  • Ballester R, Marchuk D, Boguski M, Saulino A, Letcher R, Wigler M, Collins F (1990) The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins. Cell 63(4):851–859

    Article  PubMed  CAS  Google Scholar 

  • Bernardi G (2000) Isochores and the evolutionary genomics of vertebrates. Gene 241:3–17

    Article  PubMed  CAS  Google Scholar 

  • Bernards A, Snijders AJ, Hannigan GE, Murthy AE, Gusella JF (1993) Mouse neurofibromatosis type 1 cDNA sequence reveals high degree of conservation of both coding and non-coding mRNA segments. Hum Mol Genet 2(6):645–650

    Article  PubMed  CAS  Google Scholar 

  • Buchberg AM, Bedigian HG, Jenkins NA, Copeland NG (1990) Evi-2, a common integration site involved in murine myeloid leukemogenesis. Mol Cell Biol 10(9):4658–4666

    PubMed  CAS  Google Scholar 

  • Cawthon RM, O’Connell P, Buchberg AM, Viskochil D, Weiss RB, Culver M, Stevens J, Jenkins NA, Copeland NG, White R (1990) Identification and characterization of transcripts from the neurofibromatosis 1 region: the sequence and genomic structure of EVI2 and mapping of other transcripts. Genomics 7(4):555–565

    Article  PubMed  CAS  Google Scholar 

  • Cawthon RM, Andersen LB, Buchberg AM, Xu GF, O’Connell P, Viskochil D, Weiss RB, Wallace MR, Marchuk DA, Culver M et al (1991) cDNA sequence and genomic structure of EV12B, a gene lying within an intron of the neurofibromatosis type 1 gene. Genomics 9(3):446–460

    Article  PubMed  CAS  Google Scholar 

  • Costantini M, Clay O, Auletta F, Bernardi G (2006) An isochore map of human chromosomes. Genome Res 16:536–541

    Article  PubMed  CAS  Google Scholar 

  • Cunningham LA, Coté AG, Cam-Ozdemir C, Lewis SM (2003) Rapid, stabilizing palindrome rearrangements in somatic cells by the center-break mechanism. Mol Cell Biol 23:8740–8750

    Article  PubMed  CAS  Google Scholar 

  • D’Angelo I, Welti S, Bonneau F, Scheffzek K (2006) A novel bipartite phospholipid-binding module in the neurofibromatosis type 1 protein. EMBO Rep 7(2):174–179

    Article  PubMed  Google Scholar 

  • Eisenbarth I, Vogel G, Krone W, Vogel W, Assum G (2000) An isochore transition in the NF1 gene region coincides with a switch in the extent of linkage disequilibrium. Am J Hum Genet 67:873–880

    Article  PubMed  CAS  Google Scholar 

  • Farah JA, Hartsuiker E, Mizuno K, Ohta K, Smith GR (2002) A 160-bp palindromic is a Rad50 Rad32-dependent mitotic recombination hotspot in Schizosaccharomyces pombe. Genetics 161:461–468

    PubMed  CAS  Google Scholar 

  • Feng DF, Cho G, Doolittle RF (1997) Determining divergence times with a protein clock: update and reevaluation. Proc Natl Acad Sci USA 94(24):13028–13033

    Article  PubMed  CAS  Google Scholar 

  • Gao Q, Jin K, Ying SH, Zhang Y, Xiao G, Shang Y, Duan Z, Hu X, Xie XQ, Zhou G, Peng G, Luo Z, Huang W, Wang B, Fang W, Wang S, Zhong Y, Ma LJ, St Leger RJ, Zhao GP, Pei Y, Feng MG, Xia Y, Wang C (2011) Genome sequencing and comparative transcriptomics of the model entomopathogenic fungi Metarhizium anisopliae and M. acridum. PLoS Genet 7(1):e1001264

    Article  PubMed  CAS  Google Scholar 

  • Gutmann DH, Wood DL, Collins FS (1991) Identification of the neurofibromatosis type 1 gene product. Proc Natl Acad Sci USA 88(21):9658–9662

    Article  PubMed  CAS  Google Scholar 

  • Golovnina K, Blinov A, Chang LS (2006) Evolution and origin of neurofibromin, the product of the neurofibromatosis type 1 (NF1) tumor-suppressor gene. BGRS 3(5):142–146

    Google Scholar 

  • Inagaki H, Ohye T, Kogo H, Yamada K, Kowa H, Shaikh TH, Emanuel BS, Kurahashi H (2005) Palindromic AT-rich repeat in the NF1 gene is hypervariable in humans and evolutionarily conserved in primates. Hum Mutat 26(4):332–342

    Article  PubMed  CAS  Google Scholar 

  • Jeffries TW, Grigoriev IV, Grimwood J, Laplaza JM, Aerts A, Salamov A, Schmutz J, Lindquist E, Dehal P, Shapiro H, Jin YS, Passoth V, Richardson PM (2007) Genome sequence of the lignocellulose-bioconverting and xylose-fermenting yeast Pichia stipitis. Nat Biotechnol 25(3):319–326

    Article  PubMed  CAS  Google Scholar 

  • Kehrer-Sawatzki H, Haussler J, Krone W, Bode H, Jenne DE, Mehnert KU, Tummers U, Assum G (1997) The second case of a t(17;22) in a family with neurofibromatosis type 1: sequence analysis of the breakpoint regions. Hum Genet 99:237–247

    Article  PubMed  CAS  Google Scholar 

  • Kehrer-Sawatzki H, Maier C, Moschgath E, Elgar G, Krone W (1998) Genomic characterization of the neurofibromatosis type 1 gene of Fugu rubripes. Gene 222(1):145–153

    Article  PubMed  CAS  Google Scholar 

  • Kurahashi H, Shaikh T, Takata M, Toda T, Emanuel BS (2003) The constitutional t(17;22): another translocation mediated by palindromic AT-rich repeats. Am J Hum Genet 72:733–738

    Article  PubMed  CAS  Google Scholar 

  • Mikol DD, Alexakos MJ, Bayley CA, Lemons RS, Le Beau MM, Stefansson K (1990) Structure and chromosomal localization of the gene for the oligodendrocyte-myelin glycoprotein. J Cell Biol 111(6 Pt 1):2673–2679

    Article  PubMed  CAS  Google Scholar 

  • Mikol DD, Rongnoparut P, Allwardt BA, Marton LS, Stefansson K (1993) The oligodendrocyte-myelin glycoprotein of mouse: primary structure and gene structure. Genomics 17(3):604–610

    Article  PubMed  CAS  Google Scholar 

  • O’Connell P, Viskochil D, Buchberg AM, Fountain J, Cawthon RM, Culver M, Stevens J, Rich DC, Ledbetter DH, Wallace M et al (1990) The human homolog of murine Evi-2 lies between two von Recklinghausen neurofibromatosis translocations. Genomics 7(4):547–554

    Article  PubMed  Google Scholar 

  • Saavedra RA, Fors L, Aebersold RH, Arden B, Horvath S, Sanders J, Hood L (1989) The myelin proteins of the shark brain are similar to the myelin proteins of the mammalian peripheral nervous system. J Mol Evol 29(2):149–156

    Article  PubMed  CAS  Google Scholar 

  • Schmegner C, Berger A, Vogel W, Hameister H, Assum G (2005a) An isochore transition zone in the NF1 gene region is a conserved landmark of chromosome structure and function. Genomics 86:439–445

    Article  PubMed  CAS  Google Scholar 

  • Schmegner C, Hoegel J, Vogel W, Assum G (2005b) Genetic variability in a genomic region with long-range linkage disequilibrium reveals traces of a bottleneck in the history of the European population. Hum Genet 118:276–286

    Article  PubMed  Google Scholar 

  • Schmegner C, Hameister H, Vogel W, Assum G (2007) Isochores and replication time zones: a perfect match. Cytogenet Genome Res 116:167–172

    Article  PubMed  CAS  Google Scholar 

  • The I, Hannigan GE, Cowley GS, Reginald S, Zhong Y, Gusella JF, Hariharan IK, Bernards A (1997) Rescue of a Drosophila NF1 mutant phenotype by protein kinase A. Science 276(5313):791–794

    Article  PubMed  CAS  Google Scholar 

  • Viskochil D, Cawthon R, O’Connell P, Xu GF, Stevens J, Culver M, Carey J, White R (1991) The gene encoding the oligodendrocyte-myelin glycoprotein is embedded within the neurofibromatosis type 1 gene. Mol Cell Biol 11(2):906–912

    PubMed  CAS  Google Scholar 

  • Vourc’h P, Moreau T, Arbion F, Marouillat-Védrine S, Müh JP, Andres C (2003) Oligodendrocyte myelin glycoprotein growth inhibition function requires its conserved leucine-rich repeat domain, not its glycosylphosphatidyl-inositol anchor. J Neurochem 85(4):889–897

    Article  PubMed  Google Scholar 

  • Waehneldt TV (1990) Phylogeny of myelin proteins. Ann N Y Acad Sci 605:15–28

    Article  PubMed  CAS  Google Scholar 

  • Wohlbach DJ, Kuo A, Sato TK, Potts KM, Salamov AA, Labutti KM, Sun H, Clum A, Pangilinan JL, Lindquist EA, Lucas S, Lapidus A, Jin M, Gunawan C, Balan V, Dale BE, Jeffries TW, Zinkel R, Barry KW, Grigoriev IV, Gasch AP (2011) Comparative genomics of xylose-fermenting fungi for enhanced biofuel production. Proc Natl Acad Sci USA 108(32):13212–13217

    Article  PubMed  CAS  Google Scholar 

  • Xu G, O’Connell P, Stevens J, White R (1992) Characterization of human adenylate kinase 3 (AK3) cDNA and mapping of the AK3 pseudogene to an intron of the NF1 gene. Genomics 13(3):537–542

    Article  PubMed  CAS  Google Scholar 

  • Yoshida M, Colman DR (1996) Parallel evolution and coexpression of the proteolipid proteins and protein zero in vertebrate myelin. Neuron 16(6):1115–1126

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Anatomy and Cell Biology, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany

    Britta Bartelt-Kirbach

  2. Institute of Human Genetics, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany

    Dieter Kaufmann

Authors
  1. Britta Bartelt-Kirbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dieter Kaufmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dieter Kaufmann .

Editor information

Editors and Affiliations

  1. School of Medicine, Institute of Medical Genetics, Cardiff University, Heath Park Campus, Cardiff, 144XN, United Kingdom

    Meena Upadhyaya

  2. School of Medicine, Institute of Medical Genetics, Cardiff University, Heath Park, Cardiff, CF14 4XN, United Kingdom

    David N. Cooper

Software Used

Software Used

17.1.1 BLAST

  • Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25(17):3389–3402

  • Altschul SF, Wootton JC, Gertz EM, Agarwala R, Morgulis A, Schäffer AA, Yu YK (2005) Protein database searches using compositionally adjusted substitution matrices. FEBS J 272(20):5101–5109

17.1.2 EnsEmbl

  • Flicek P, Amode MR, Barrell D, Beal K, Brent S, Carvalho-Silva D, Clapham P, Coates G, Fairley S, Fitzgerald S, Gil L, Gordon L, Hendrix M, Hourlier T, Johnson N, Kähäri AK, Keefe D, Keenan S, Kinsella R, Komorowska M, Koscielny G, Kulesha E, Larsson P, Longden I, McLaren W, Muffato M, Overduin B, Pignatelli M, Pritchard B, Riat HS, Ritchie GR, Ruffier M, Schuster M, Sobral D, Tang YA, Taylor K, Trevanion S, Vandrovcova J, White S, Wilson M, Wilder SP, Aken BL, Birney E, Cunningham F, Dunham I, Durbin R, Fernández-Suarez XM, Harrow J, Herrero J, Hubbard TJ, Parker A, Proctor G, Spudich G, Vogel J, Yates A, Zadissa A, Searle SM (2012) Ensembl 2012. Nucleic Acids Res 40(database issue):D84–D90

17.1.3 EnsEmbl GeneTree

  • Vilella AJ, Severin J, Ureta-Vidal A, Durbin A, Heng L, Birney E (2009) EnsemblCompara GeneTrees: Analysis of complete, duplication-aware phylogenetic trees in vertebrates. Genome Res 19:327–335

17.1.4 dbSNP NCBI

  • Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, Smigielski EM, Sirotkin K (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29(1):308–311

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Bartelt-Kirbach, B., Kaufmann, D. (2012). Insights into NF1 from Evolution. In: Upadhyaya, M., Cooper, D. (eds) Neurofibromatosis Type 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-32864-0_17

Download citation

Publish with us

Policies and ethics

Search

Navigation