Advertisement

Bulletin of Mathematical Biology

, Volume 80, Issue 10, pp 2734–2760 | Cite as

The Duplexing of the Genetic Code and Sequence-Dependent DNA Geometry

  • Alex Kasman
Original Article

Abstract

It is well known that sequences of bases in DNA are translated into sequences of amino acids in cells via the genetic code. More recently, it has been discovered that the sequence of DNA bases also influences the geometry and deformability of the DNA. These two correspondences represent a naturally arising example of duplexed codes, providing two different ways of interpreting the same DNA sequence. This paper will set up the notation and basic results necessary to mathematically investigate the relationship between these two natural DNA codes. It then undertakes two very different such investigations: one graphical approach based only on expected values and another analytic approach incorporating the deformability of the DNA molecule and approximating the mutual information of the two codes. Special emphasis is paid to whether there is evidence that pressure to maximize the duplexing efficiency influenced the evolution of the genetic code. Disappointingly, the results fail to support the hypothesis that the genetic code was influenced in this way. In fact, applying both methods to samples of realistic alternative genetic codes shows that the duplexing of the genetic code found in nature is just slightly less efficient than average. The implications of this negative result are considered in the final section of the paper.

Keywords

Genetic code DNA geometry Mutual information Multiplexing Codons 

Notes

Acknowledgements

I am grateful to Jason Cantarella (University of Georgia), Madison Hyer (Medical University of South Carolina), Martin Jones (College of Charleston), Brenton Lemesurier (College of Charleston), Garrett Mitchener (College of Charleston), and Laura Kasman (Medical University of South Carolina) for helpful discussion and feedback. I would also like to thank Wilma Olson and the organizers of the Thematic Year on Mathematics of Molecular and Cellular Biology at the IMA where I met her and first learned about the sequence-dependent geometry of DNA.

References

  1. Alexander RW, Schimmel P (2001) Wobble hypothesis. In: Brenner S, Miller JH (eds) Encyclopedia of genetics. Elsevier, AmsterdamGoogle Scholar
  2. Barrell BG, Bankier AT, Drouin J (1979) A different genetic code in human mitochondria. Nature 282:189–194CrossRefGoogle Scholar
  3. Berg JM, Tymoczko JL, Stryer L (2002) Biochemistry, 5th edn. WH Freeman, New York. Section 5.5.1Google Scholar
  4. Eslami-Mossallam B, Schram RD, Tompitak M, van Noort John, Schiessel H, (2016) Multiplexing genetic and nucleosome positioning codes: a computational approach. PLoS One 11(6):e0156905.  https://doi.org/10.1371/journal.pone.0156905 CrossRefGoogle Scholar
  5. Fujii S, Kono H, Takenaka S, Go N, Sarai A (2007) Sequence-dependent DNA deformability studied using molecular dynamics simulations. Nucleic Acids Res 35(18):6063–6074CrossRefGoogle Scholar
  6. Hassan MA, Calladine CR (1995) The assessment of the geometry of dinucleotide steps in double-helical DNA; a new local calculation scheme. J Mol Biol 251:648–664CrossRefGoogle Scholar
  7. Itzkovitz S, Alon U (2007) The genetic code is nearly optimal for allowing additional information within protein-coding sequences. Genom Res 17(4):405–12 Epub 2007 Feb 9CrossRefGoogle Scholar
  8. Kawaguchi Y, Honda H, Taniguchi-Morimura J, Iwasaki S (1989) The codon CUG is read as serine in an asporogenic yeast Candida cylindracea. Nature 341:164–166CrossRefGoogle Scholar
  9. Kiga D, Sakamoto K, Kodama K, Kigawa T, Matsuda T, Yabuki T, Shirouzu M, Harada Y, Nakayama H, Takio K (2002) An engineered Escherichia coli tyrosyl-tRNA synthetase for site-specific incorporation of an unnatural amino acid into proteins in eukaryotic translation and its application in a wheat germ cell-free system. Proc Natl Acad Sci USA 99:9715–9720CrossRefGoogle Scholar
  10. Koonin EV, Novozhilov AS (2017) Origin and evolution of the universal genetic code. Annu Rev Genet 51:4562CrossRefGoogle Scholar
  11. Kumara B, Saini S (2016) Analysis of the optimality of the standard genetic code. Mol BioSyst 12:2642–2651CrossRefGoogle Scholar
  12. Lajoie MJ, Söll D, Church GM (2016) Overcoming challenges in engineering the genetic code. J Mol Biol 428(5 Pt B):10041021CrossRefGoogle Scholar
  13. Lankas F, Sponer J, Langowski J, Thomas E (2003) Cheatham III. DNA basepair step deformability inferred from molecular dynamics simulations. Biophys J 85:2872–2883CrossRefGoogle Scholar
  14. Liu CC, Schultz PG (2010) Adding new chemistries to the genetic code. Annu Rev Biochem 79:413–444CrossRefGoogle Scholar
  15. Matsumoto A, Olson WK (2002) Sequence-dependent motions of DNA: a normal mode analysis at the base-pair level. Biophys J 83:22–41CrossRefGoogle Scholar
  16. Olson WK, Gorin AA, Xiang-Jun L, Hock LM, Zhurkin Victor B (1998) DNA sequence-dependent deformability deduced from protein-DNA crystal complexes. Proc Natl Acad Sci USA 95:11163–11168CrossRefGoogle Scholar
  17. Rohs R, West SM, Sosinsky A et al (2009) The role of DNA shape in protein-DNA recognition. Nature 461(7268):1248–1281CrossRefGoogle Scholar
  18. Srinivasan G, James CM (2002) Pyrrolysine encoded by UAG in Archaea. Science 296(5572):1459–1462CrossRefGoogle Scholar
  19. Wang L, Brock A, Herberich B, Schultz PG (2001) Expanding the genetic code of Escherichia coli. Science 292:498–500CrossRefGoogle Scholar
  20. Yamao F, Muto A, Kawauchi Y, Iwami M, Iwagami S, Azumi Y, Osawa S (1985) UGA is read as tryptophan in Mycoplasma capricolum. Proc Natl Acad Sci USA 82:2306–2309CrossRefGoogle Scholar
  21. Zhang Z, Yu J (2011) On the organizational dynamics of the genetic code. Genom Proteomics Bioinform 9(1–2):21–29CrossRefGoogle Scholar

Copyright information

© Society for Mathematical Biology 2018

Authors and Affiliations

  1. 1.College of CharlestonCharlestonUSA

Personalised recommendations