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A Purine-Pyrimidine Classification Scheme of the Genetic Code

Institute of Molecular Biotechnology. Jena. A Purine-Pyrimidine Classification Scheme of the Genetic Code. Swetlana Nikolajewa, Thomas Wilhelm Theoretical Systems Biology. Overview. The genetic code - introduction The new classification scheme of the genetic code shows:

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A Purine-Pyrimidine Classification Scheme of the Genetic Code

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  1. Institute of Molecular Biotechnology Jena A Purine-Pyrimidine Classification Scheme of the Genetic Code Swetlana Nikolajewa, Thomas Wilhelm Theoretical Systems Biology

  2. Overview • The genetic code - introduction • The new classification scheme of the genetic code shows: • symmetry characteristics • explanation for the number (22) of tRNA genes in mammalian mitochondrial genome • amino-acids patterns and regularities of codons (strong, mixed and weak codons) • possible predecessors of our contemporary quaternary triplet code

  3. The Genetic Code • 3 nucleotidesbases (triplets) of A, G, C, U are used to code for 20 amino acids • two purines (A,G) • two pyrimidines (C,U) • 64 possible codons (4x4x4=43) • 3 termination codons: UGA, UA(G/A) • 61 codons for amino acid coding • Met (AUG) codon is also the start codon

  4. The Common Genetic Code Table

  5. The new classification scheme of the genetic code • binary representation of • purines(A,G) → 1 • pyrimidines(C,U) → 0 • 23 = 8 different binary triplets 000 , 001, … ,111each of these has again 8 possibilities, for instance: • 000 stands for three pyrimidines: CCC, CCU, UUC, …, UUU • 111 stands for three purines: GGG, GGA, GAA, …,AAA • CG binds via 3hydrogen bonds in the complementary base-paring • AUbinds via 2 hydrogen bonds in the complementary base-paring

  6. The Common Genetic Code Table The Common Genetic Code Table contains 64 fields…

  7. The new classification scheme (standard genetic code) Mixedcodons 5 hydrogen bonds Code Strongcodons 6 hydrogen bonds Mixedcodons 5 hydrogen bonds Weakcodons 4 hydrogen bonds 000 ProCC (C/U) Proline SerUC (C/U) Serine LeuCU(C/U) Leucine PheUU(C/U) Phenylalanine SerUC(A/G) Serine LeuUU(A/G) Leucine ProCC(A/G) Proline LeuCU(A/G) Leucine 001 ThrAC(C/U) Threonine Ala GC(C/U) Alanine IleAU(C/U) Isoleucine ValGU(C/U) Valine 100 AlaGC(A/G) Alanine ThrAC(A/G) Threonine ValGU(A/G) Valine 101 Ile/MetAU(A/G) Isoleucine/Methionine ArgCG(C/U) Arginine CysUG(C/U) Cystein 010 HisCA (C/U) Histidine TyrUA(C/U) Tyrosine StopUA(A/G) GlnCA (A/G) Glutamine ArgCG(A/G) Arginine 011 Stop/TrpUG(A/G) Tryptophan AsnAA(C/U) Asparagine GlyGG(C/U) Glycine 110 SerAG(C/U) Serine AspGA(C/U) Asparaticacid GlyGG(A/G) Glycine ArgAG(A/G) Arginine LysAA(A/G) Lysine GluGA(A/G) Glutamaticacid 111 the new scheme contains the same information in only 32 fields.

  8. Deviations from the Standard Code Mixedcodons 5 hydrogen bonds Code Strongcodons 6 hydrogen bonds Mixedcodons 5 hydrogen bonds Weakcodons 4 hydrogen bonds 000 ProCC (C/U) SerUC (C/U) LeuCU(C/U) 1/1 PheUU(C/U) ProCC(A/G) SerUC(A/G) 1/0 001 LeuUU(A/G) 1/0 LeuCU(A/G) 1/2 100 ThrAC(C/U) AlaGC(C/U) IleAU(C/U) ValGU(C/U) 101 Ile/MetAU(A/G) 5/0 AlaGC(A/G) ThrAC(A/G) ValGU(A/G) ArgCG(C/U) CysUG(C/U) 010 HisCA (C/U) TyrUA(C/U) StopUA(A/G) 2/4 GlnCA (A/G) ArgCG(A/G) 011 Stop /TrpUG(A/G) 9/0 AsnAA(C/U) GlyGG(C/U) 110 SerAG(C/U) AspGA(C/U) LysAA(A/G) 3/0 GlyGG(A/G) ArgAG(A/G) 6/6 GluGA(A/G) 111 http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi

  9. Mitochondrial Genomes Have Several Surprising Features • genetic code of mitochondria • only22 tRNAs are required for mammalian mitochondrial protein synthesis

  10. The Mammalian Mitochondrial Genetic Code Mixedcodons 5 hydrogen bonds Code Strongcodons 6 hydrogen bonds Mixedcodons 5 hydrogen bonds Weakcodons 4 hydrogen bonds 000 ProCC (C/U) SerUC (C/U) LeuCU(C/U) PheUU(C/U) ProCC(A/G) SerUC(A/G) 001 LeuUU(A/G) LeuCU(A/G) 100 ThrAC(C/U) AlaGC(C/U) IleAU(C/U) ValGU(C/U) 101 Met/MetAU(A/G) AlaGC(A/G) ThrAC(A/G) ValGU(A/G) ArgCG(C/U) CysUG(C/U) 010 HisCA (C/U) TyrUA(C/U) StopUA(A/G) GlnCA (A/G) ArgCG(A/G) 011 Trp /TrpUG(A/G) AsnAA(C/U) GlyGG(C/U) 110 SerAG(C/U) AspGA(C/U) LysAA(A/G) GlyGG(A/G) STOPAG(A/G) GluGA(A/G) 111 http://www.ncbi.nlm.nih.gov/Taxonomy/Utils/wprintgc.cgi

  11. The Mammalian Mitochondrial Code:8 tRNAs for family codons + 14 tRNAs for non-family codons Mixedcodons 5 hydrogen bonds Code Strongcodons 6 hydrogen bonds Mixedcodons 5 hydrogen bonds Weakcodons 4 hydrogen bonds 000 tRNAPheUU(C/U) tRNALeu1CU tRNASer1UC tRNAProCC tRNALeu2UU(A/G) 001 tRNAValGU tRNAThrAC tRNAIleAU(C/U) tRNAAlaGC 100 101 tRNAMetAU(A/G) tRNAArgCG tRNACysUG (C/U) 010 tRNAHisCA (C/U) tRNATyrUA(C/U) STOPUA(A/G) tRNAGlnCA (A/G) 011 tRNATrpUG (A/G) tRNAAsnAA(C/U) tRNAGlyGG 110 tRNASer2AG (C/U) tRNAAspGA(C/U) tRNALysAA(A/G) STOPAG(A/G) tRNAGluGA(A/G) 111 http://mamit-trna.u-strasbg.fr/2DStructures.html

  12. Amino acids patterns: Polar requirement of NCN and NUN codons Mixedcodons 5 hydrogen bonds Code Strongcodons 6 hydrogen bonds Mixedcodons 5 hydrogen bonds Weakcodons 4 hydrogen bonds 000 ProCC (C/U) SerUC (C/U) LeuCU(C/U) PheUU(C/U) ProCC(A/G) SerUC(A/G) 001 LeuUU(A/G) LeuCU(A/G) 100 ThrAC(C/U) AlaGC(C/U) IleAU(C/U) ValGU(C/U) 101 Ile/MetAU(A/G) AlaGC(A/G) ThrAC(A/G) ValGU(A/G) ArgCG(C/U) CysUG(C/U) 010 HisCA (C/U) TyrUA(C/U) StopUA(A/G) GlnCA (A/G) ArgCG(A/G) 011 Stop/TrpUG(A/G) AsnAA(C/U) Asparagine GlyGG(C/U) 110 SerAG(C/U) AspGA(C/U) Asparaticacid GlyGG(A/G) ArgAG(A/G) LysAA(A/G) Lysine GluGA(A/G) Glutamaticacid 111 C. R. Woese, G. J. Olsen, M. Ibba, D. Söll Aminoacyl-tRNA Synthetases, the Genetic Code, and the Evolutionary Process. MMBR 2000(64) 202-236

  13. Amino acids patterns: Hydrophobicity. Mixedcodons 5 hydrogen bonds Code Strongcodons 6 hydrogen bonds Mixedcodons 5 hydrogen bonds Weakcodons 4 hydrogen bonds 000 ProCC (C/U) SerUC (C/U) LeuCU(C/U) PheUU(C/U) ProCC(A/G) SerUC(A/G) 001 LeuUU(A/G) LeuCU(A/G) 100 ThrAC(C/U) AlaGC(C/U) IleAU(C/U) ValGU(C/U) 101 Ile/MetAU(A/G) AlaGC(A/G) ThrAC(A/G) ValGU(A/G) ArgCG(C/U) CysUG(C/U) 010 HisCA (C/U) TyrUA(C/U) StopUA(A/G) GlnCA (A/G) ArgCG(A/G) 011 Stop/TrpUG(A/G) AsnAA(C/U) GlyGG(C/U) 110 SerAG(C/U) AspGA(C/U) GlyGG(A/G) ArgAG(A/G) LysAA(A/G) GluGA(A/G) 111 Kyte&Doolittle, 1982, http://biology-pages.info

  14. Codon-Anticodon symmetry Mixedcodons 5 hydrogen bonds Code Strongcodons 6 hydrogen bonds Mixedcodons 5 hydrogen bonds Weakcodons 4 hydrogen bonds 000 ProCC (C/U) SerUC (C/U) LeuCU(C/U) PheUU(C/U) ProCC(A/G) SerUC(A/G) 001 LeuUU(A/G) LeuCU(A/G) 100 ThrAC(C/U) AlaGC(C/U) IleAU(C/U) ValGU(C/U) 101 Ile/MetAU(A/G) AlaGC(A/G) ThrAC(A/G) ValGU(A/G) ArgCG(C/U) CysUG(C/U) 010 HisCA (C/U) TyrUA(C/U) StopUA(A/G) GlnCA (A/G) ArgCG(A/G) 011 Stop/TrpUG(A/G) AsnAA(C/U) GlyGG(C/U) 110 SerAG(C/U) AspGA(C/U) LysAA(A/G) GlyGG(A/G) ArgAG(A/G) GluGA(A/G) 111

  15. Point symmetry Mixedcodons 5 hydrogen bonds Code Strongcodons 6 hydrogen bonds Mixedcodons 5 hydrogen bonds Weakcodons 4 hydrogen bonds 000 ProCC (C/U) SerUC (C/U) LeuCU(C/U) PheUU(C/U) ProCC(A/G) SerUC(A/G) 001 LeuUU(A/G) LeuCU(A/G) 100 ThrAC(C/U) AlaGC(C/U) IleAU(C/U) ValGU(C/U) 101 Ile/MetAU(A/G) AlaGC(A/G) ThrAC(A/G) ValGU(A/G) ArgCG(C/U) CysUG(C/U) 010 HisCA (C/U) TyrUA(C/U) StopUA(A/G) GlnCA (A/G) ArgCG(A/G) 011 Stop/TrpUG(A/G) AsnAA(C/U) GlyGG(C/U) 110 SerAG(C/U) AspGA(C/U) GlyGG(A/G) ArgAG(A/G) LysAA(A/G) GluGA(A/G) 111 D. HalitskyExtending the (Hexa-)Rhombic Dodecahedral Model of the Genetic Code: the Code's Four 6-fold Degeneracies and the Ten Orthogonal Projections of the 5-cube as 3-cube. Computer Systems Technology 2004

  16. Correlation of codon strength and amino acid properties

  17. CGU, UAC,… Evolution of the genetic code • our contemporary code is the quaternary triplet code: 43=64 fields • binary doublet: 41=4 fields CGU, UAC,… • quaternary doublet code:42=16 fields

  18. Evidence: Evolution of the Genetic Code Mixedcodons 5 hydrogen bonds Code Strongcodons 6 hydrogen bonds Mixedcodons 5 hydrogen bonds Weakcodons 4 hydrogen bonds 000 ProCC (C/U) Proline SerUC (C/U) Serine LeuCU(C/U) Leucine PheUU(C/U) Phenylalanine SerUC(A/G) Serine LeuUU(A/G) Leucine ProCC(A/G) Proline LeuCU(A/G) Leucine 001 ThrAC(C/U) Threonine AlaGC(C/U) Alanine IleAU(C/U) Isoleucine ValGU(C/U) Valine 100 AlaGC(A/G) Alanine ThrAC(A/G) Threonine ValGU(A/G) Valine 101 Ile/MetAU(A/G) Isoleucine/Methionine ArgCG(C/U) Arginine CysUG(C/U) Cystein 010 HisCA (C/U) Histidine TyrUA(C/U) Tyrosine StopUA(A/G) GlnCA (A/G) Glutamine ArgCG(A/G) Arginine 011 Stop/TrpUG(A/G) Tryptophan AsnAA(C/U) Asparagine GlyGG(C/U) Glycine 110 SerAG(C/U) Serine AspGA(C/U) Asparaticacid GlyGG(A/G) Glycine ArgAG(A/G) Arginine LysAA(A/G) Lysine GluGA(A/G) Glutamaticacid 111

  19. Evidence: Evolution of the Genetic Code Mixedcodons 5 hydrogen bonds Code Strongcodons 6 hydrogen bonds Mixedcodons 5 hydrogen bonds Weakcodons 4 hydrogen bonds 000 ProCC (C/U) Proline SerUC (C/U) Serine LeuCU(C/U) Leucine PheUU(C/U) Phenylalanine SerUC(A/G) Serine LeuUU(A/G) Leucine ProCC(A/G) Proline LeuCU(A/G) Leucine 001 ThrAC(C/U) Threonine AlaGC(C/U) Alanine IleAU(C/U) Isoleucine ValGU(C/U) Valine 100 AlaGC(A/G) Alanine ThrAC(A/G) Threonine ValGU(A/G) Valine 101 Ile/MetAU(A/G) Isoleucine/Methionine ArgCG(C/U) Arginine CysUG(C/U) Cystein 010 HisCA (C/U) Histidine TyrUA(C/U) Tyrosine StopUA(A/G) GlnCA (A/G) Glutamine ArgCG(A/G) Arginine 011 Stop/TrpUG(A/G) Tryptophan AsnAA(C/U) Asparagine GlyGG(C/U) Glycine 110 SerAG(C/U) Serine AspGA(C/U) Asparaticacid GlyGG(A/G) Glycine ArgAG(A/G) Arginine LysAA(A/G) Lysine GluGA(A/G) Glutamaticacid 111

  20. Outlook • Looking for binary patterns in the genomes • Additional information http://www.imb-jena.de/~sweta/genetic_code/ • Acknowledgment Maik Friedel Andreas Beyer Frank Grosse Thankyouforyourattention!

  21. The new classification scheme of the standard genetic code Mixedcodons 5 hydrogen bonds Code Strongcodons 6 hydrogen bonds Mixedcodons 5 hydrogen bonds Weakcodons 4 hydrogen bonds 000 ProCC (C/U) Proline SerUC (C/U) Serine LeuCU(C/U) Leucine PheUU(C/U) Phenylalanine SerUC(A/G) Serine LeuUU(A/G) Leucine ProCC(A/G) Proline LeuCU(A/G) Leucine 001 ThrAC(C/U) Threonine AlaGC(C/U) Alanine IleAU(C/U) Isoleucine ValGU(C/U) Valine 100 AlaGC(A/G) Alanine ThrAC(A/G) Threonine ValGU(A/G) Valine 101 Ile/MetAU(A/G) Isoleucine/Methionine ArgCG(C/U) Arginine CysUG(C/U) Cystein 010 HisCA (C/U) Histidine TyrUA(C/U) Tyrosine StopUA(A/G) GlnCA (A/G) Glutamine ArgCG(A/G) Arginine 011 Stop/TrpUG(A/G) Tryptophan AsnAA(C/U) Asparagine GlyGG(C/U) Glycine 110 SerAG(C/U) Serine AspGA(C/U) Asparaticacid GlyGG(A/G) Glycine ArgAG(A/G) Arginine LysAA(A/G) Lysine GluGA(A/G) Glutamaticacid 111 T.Wilhelm, S.Nikolajewa A new classification scheme of the genetic code. J. Mol. Evol. (2004) 59: 598-605

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