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Maik Friedel, Swetlana Nikolajewa, Thomas Wilhelm Theoretical Systems Biology, FLI-Jena, Germany http://www.fli-leibniz.de/tsb Abstract: We hypothesize that in the early days of translation pre-tRNAs were able to recognize codons in both directions. In order to guarantee termination and to avoid incorrect elongation the reverse stop codons should have had no own pre-tRNA. We studied the number of tRNA genes of 16 archaea, 81 bacteria and 7 eucaryotes. It was surprising that still today reverse stop codons do not have their own tRNAs (just one exception in human). Furthermore, patterns in our new classification scheme of the genetic code support speculations that the contemporary triplet code developed from an ancient doublet code. In order to avoid the frame shift problem one has to assume a triplet reading frame also in doublet coding times, which would indicate an information wasting of each third base. Our hypothesis provides a possible solution for this information wasting problem. Moreover, it could also account for additional so far unexplained facts about amino acid – codon assignments. Codon – Anticodon pairs and their corresponding number of tRNA genes. • STOP codons have no own tRNAs. • Reverse STOP codons also have no own tRNAs! Codons and the reverse codons code for either the same or a similar amino acid: Code Strong codons (6 H-bonds) Mixed codons (5 H-bonds) Mixed codons (5 H-bonds) Weak codons (4 H-bonds) 000 Pro CC (C/U) Ser UC (C/U) Leu CU (C/U) Phe UU (C/U) • The middle base of a codon determines important physical properties of the corresponding amino acid. 001 Pro CC (A/G) Ser UC (A/G) Leu CU (A/G) Leu UU (A/G) • 16 self reverse codons correspond to 15 different amino acids. 100 Ala GC (C/U) Thr AC (C/U) Val GU (C/U) Ile AU (C/U) 101 Ala GC (A/G) Thr AC (A/G) Val GU (A/G) Ile/Met AU • The triplet genetic code had a doublet predecessor. (A/G) 010 Arg CG (C/U) Cys UG (C/U) His CA (C/U) Tyr UA (C/U) 011 Arg CG (A/G) Stop/Trp UG Gln CA (A/G) Stop UA (A/G) 110 Gly GG (C/U) Ser AG (C/U) Asp GA (C/U) Asn AA (C/U) 111 Gly GG (A/G) Arg AG (A/G) Glu GA (A/G) Lys AA (A/G) (A/G) • Amino acids corresponding to codons and their reverse codons are evolutionary conserved. Copley SD et al. PNAS, 102:4442–4447, 2005 A mechanism for the association of amino acids with their codons and the origin of the genetic code. • There was always a triplet reading frame. Landweber L, Chem Biol. 9(2):237-44, 2000. Custom codons come in threes, fours, and fives. Our new classification scheme of the genetic code is based on a purine (1) – pyrimidine (0) coding. Red arrows indicate codon reverse codon pairs (XYZ<->ZYX). A new classification scheme of the genetic code Wilhelm T., Nikolajewa S., J. Mol. Evol. 59:598 – 605, 2004 Reverse recognition conjecture: In ancient times pre-tRNA was able to bind the pre-mRNA in both directions. A0 A1 U C C U A A A0 A U G Fig. 2 C U A A0 0A C C U A A A U N 5‘ N U A 3‘ codon U 5‘ 3‘ reverse codon Conclusion Fig. 1 The new hypothesis can explain all above stated facts and assumptions. It can lead to a new understanding of the early evolution of life. We assume that this sloppy translation increased the diversity of similar proteins and thus contributed to an accelerated evolution. The new classification scheme of the genetic code, its early evolution, and tRNA usage Nikolajewa S., Friedel M., Beyer A., Wilhelm T., J. Comp. Biol. & Bioinf., 2006 (in press)