Natural Computing

, Volume 6, Issue 4, pp 359–370 | Cite as

Two proteins for the price of one: the design of maximally compressed coding sequences

  • Bei Wang
  • Dimitris Papamichail
  • Steffen Mueller
  • Steven Skiena
Original Paper
  • 68 Downloads

Abstract

The emerging field of synthetic biology moves beyond conventional genetic manipulation to construct novel life forms which do not originate in nature. We explore the problem of designing the provably shortest genomic sequence to encode a given set of genes by exploiting alternate reading frames. We present an algorithm for designing the shortest DNA sequence simultaneously encoding two given amino acid sequences. We show that the coding sequence of naturally occurring pairs of overlapping genes approach maximum compression. We also investigate the impact of alternate coding matrices on overlapping sequence design. Finally, we discuss an interesting application for overlapping gene design, namely the interleaving of an antibiotic resistance gene into a target gene inserted into a virus or plasmid for amplification.

Keywords

Gene compression Gene design Protein design Overlapping genes Sequence design algorithms Synthetic biology Dynamic programming 

Notes

Acknowledgments

This research was partially supported by NSF grants EIA-0325123 and DBI-0444815. We thank Eckard Wimmer for his interest and support. We also thank Chen Zhao, Huei-Chi Chen, and Rahul Sinha for discussions and contributions to this research.

References

  1. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Molecular biology of the cell. Garland Science, New YorkGoogle Scholar
  2. Ball P (2004) Starting from scratch. Nature 431:624–626CrossRefGoogle Scholar
  3. Cann AJ (1993) Principles of molecular virology. Academic Press, LondonGoogle Scholar
  4. Cello J, Paul AV, Wimmer E (2002) Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template. Science 297:1016–1018CrossRefGoogle Scholar
  5. Cohen B, Skiena S (2003) Natural selection and algorithmic design of mrna. J Comput Biol 10:419–432CrossRefGoogle Scholar
  6. Daley M, McQuillan I (2005a) Formal modelling of viral gene compression. Int J Found Comput Sci 16(3):453–469MATHMathSciNetCrossRefGoogle Scholar
  7. Daley M, McQuillan I (2005b) Viral gene compression: complexity and verification. Lect Notes Comput Sci 3317:102–112MathSciNetCrossRefGoogle Scholar
  8. Elber R, Karplus M (1990) Enhanced sampling in molecular dynamics: use of the time-dependent hartree approximation for a simulation of carbon monoxide diffusion through myoglobin. J Am Chem Soc 112:9161–9175CrossRefGoogle Scholar
  9. Freeland S, Hurst L (2004) Evolution encoded. Sci Am 290(4):84–91CrossRefGoogle Scholar
  10. Fukuda Y, Washio T, Tomita M (1998) Evolution of overlapping genes: Comparative genomics of mycoplasma genitalium and mycoplasma pneumoniae. Genome Inform 9:254–255Google Scholar
  11. Fukuda Y, Nakayama Y, Tomita M (2003) On dynamics of overlapping genes in bacterial genomes. Gene 323:181–187CrossRefGoogle Scholar
  12. Gilis D, Massar D, Cerf NJ, Rooman M (2001) Optimality of the genetic code with respect to protein stability and amino-acid frequencies. Genome Biol 2(11):1–12Google Scholar
  13. Hornak V, Simmerling C (2003) Generation of accurate protein loop conformations through low-barrier molecular dynamics. Proteins 51:577–590CrossRefGoogle Scholar
  14. Karlin S, Chen C, Gentles A, Cleary M (2002) Associations between human disease genes and overlapping gene groups and multiple amino acid runs. Proc Natl Acad Sci 99(26):17008–17013CrossRefGoogle Scholar
  15. Keese P, Gibbs A (1992) Origins of genes: “big bang” or continuous creation? Proc Natl Acad Sci 89:9489–9493Google Scholar
  16. Kodumal S, Pael K, Reid R, Menzella H, Welch M, Santi D (2004) Total synthesis of long DNA sequences: synthesis of a contiguous 32-kb polyketide synthase gene cluster. Proc Natl Acad Sci 44:15573–15578Google Scholar
  17. Krakauer DC (2000) Stability and evolution of overlapping genes. Evolution 54(3):731–739Google Scholar
  18. Krakauer D (2002) Evolutionary principles of genomic compression. Comments Theor Biol 7:215–236CrossRefGoogle Scholar
  19. Levitt M (1976) A simplified representation of protein conformations for rapid simulation of protein folding. J Mol Biol 104:59–107CrossRefGoogle Scholar
  20. Marti-Renom MA, Stuart AC, Fiser A, Sanchez R, Melo F, Sali A (2000) Comparative protein structure modeling of genes and genomes. Annu Rev Biophys Biomol Struct 29:291–325CrossRefGoogle Scholar
  21. Miyata T, Yasunaga T (1978) Evolution of overlapping genes. Nature 272:532–535CrossRefGoogle Scholar
  22. Oppenheim D, Yahofsky C (1980) Translational coupling during expression of the tryptophan operon of E. coli. Genetics 95:785–795Google Scholar
  23. Rogozin I, Spiridonov A, Sorokin A, Wolf Y, King J, Tatusov R, Koonin E (2002) Purifying and directional selection in overlapping prokaryotic genes. Trends Genet 18(5):228–232CrossRefGoogle Scholar
  24. Skiena S (2001) Designing better phages. Bioinformatics 17:253–261Google Scholar
  25. Skiena S, Wimmer E (2003) Gene design for vaccines and theraputic phages. NSF ITR Award 0325123Google Scholar
  26. Smith H, Hutchison C, Pfannkoch C, Venter JC (2003) Generating a synthetic genome by whole genome assembly: phix174 bacteriophage from synthetic oligonucleotides. Proc Natl Acad Sci 100:15440–15445Google Scholar
  27. Tian J, Gong H, Sheng N, Zhou Z, Gulari E, Gao X, Church G (2004) Accurate multiplex gene synthesis from programmable DNA microchips. Nature 432:1050–1054CrossRefGoogle Scholar
  28. Veeramachaneni V, Makalowski W, Galdzicki M, Sood R, Makalowska I (2004) Mammalian overlapping genes: the comparative method. Genome Res 14:280–286CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Bei Wang
    • 1
  • Dimitris Papamichail
    • 2
  • Steffen Mueller
    • 3
  • Steven Skiena
    • 2
  1. 1.Department of Computer ScienceDuke UniversityDurhamUSA
  2. 2.Department of Computer ScienceState University of New YorkStony BrookUSA
  3. 3.Department of MicrobiologyState University of New YorkStony BrookUSA

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