Abstract
An examination of 51 mRNA sequences in GENBANK has revealed that calculated mRNA folding free energies are more negative than expected. Free energy minimization calculations of native mRNA sequences are more negative than randomized mRNA sequences with the same base composition and length. Randomization only of the coding region of genes also yields folding free energies of less negative magnitude than the original native mRNA sequence. Examination of the predicted basepairing within the coding sequence finds an unequal distribution between the three possible frames. The wobble-to-1 frame, which is ”in-frame”, is preferred significantly compared to randomized sets of mRNA sequences. This suggests that evolution may bias or adjust the local selection of codons to favor the global formation of more mRNA structures. This would result in greater negative folding free energies as seen in the 51 mRNAs examined.
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References
de Smit, M.H and van Duin, J. (1990),”Control of translation by mRNA secondary structure in Escherichia coli. A quantitative analysis of literature data,” J Mol Biol 1994 Nov 25;244(2):144–50.
Devereux, J., Haeberli, P., and Smithies, O. (1984), ”A comprehensive set of sequence analysis programs for the VAX,” Nuc. Acids Res.,12, 387–395.
Hofacker IL, Fekete M, Flamm C, Huynen MA, Rauscher S, Stolorz PE, Stadler PF (1998),”Automatic detection of conserved RNA structure elements in complete RNA virus genomes,” Nucleic Acids Res 1998 Aug 15; 26 (16):3825–36.
Jacobson, A.B., Arora, R., Zuker, M., Priano, C., Lin, C.H., & Mills, D.R. (1998),”Structural plasticity in RNA and its role in the regulation of protein translation in coliphage Q beta,” J. Mol. Biol. 275, 589–600.
Joyce, G. (1997),”Evolutionary chemistry: getting there from here,” Science 13; 276 (5319):1658–9.
Karlin, S. and Mrazek, J. (1996), ”What drives codon choices in human genes?,” J. Mol. Biol. 262:459–472.
Le, S.-Y. and Maizel, J.V., Jr. (1989), ”A method for assessing the statistical significance of RNA folding,” J. Theor. Biol., 138,495–510.
Lloyd, A.T. and Sharp, P.M. (1992), ”Evolution of codon usage patterns: the extent and nature of divergence between Candida albicans and Saccharomyces cerevisiae.,” Nuc. Acids Res.,20,5289–5295.
Love Jr., H.D., Allen-Nash, A., Zhao, Q., and Bannon, G.A. (1988), ”mRNA stability plays a major role in regulating the temperature–specific expression of a Tetrahymena thermophila surface protein,” Mol. Cell. Biol.,8,427–432.
Macdonald PM, Kerr K (1997), ”Redundant RNA recognition events in bicoid mRNA localization,” RNA 1997 Dec; 3(12):1413–20.
Mathews DH, Sabina J, Zuker M, Turner DH (1999), ”Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure,” J Mol Biol 1999 May 21;288 (5):911–40
Seffens, W. and Digby, D., (1999), ”mRNAs Have Greater Calculated Folding Free Energies Than Shuffled or Codon Choice Randomized Sequences,” Nucleic Acids Research, 27,1578–1584.
Seffens, W. (1999), ”Graph generation and properties of the standard genetic code,” Mathematica World, submitted.
Zuker, M. and Stieler P. 1981 ”Optimal computer folding of large RNA sequences, using thermodynamics and auxiliary information.,” Nuc. Acids Res.,9,133–148.
Zull, J.E. and Smith, S.K. (1990), ”Is genetic code redundancy related to retention of structural information in both DNA strands?,” Trends Biochemical Sci., 15,257–261.
Walter, A.E., Turner, D.H., Kim, J., Lyttle, M.H., Müller, P., Mathews, D.H., and Zuker, M. (1994), ”Coaxial stacking of helixes enhances binding of oligoribonucleotides and improves predictions of RNA folding,” Proc. Natl. Acad. Sci. USA 91, 9218–9222.
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© 2000 Springer Science+Business Media Dordrecht
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Seffens, W., Digby, D. (2000). Gene Sequences are Locally Optimized for Global mRNA Folding. In: Floudas, C.A., Pardalos, P.M. (eds) Optimization in Computational Chemistry and Molecular Biology. Nonconvex Optimization and Its Applications, vol 40. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-3218-4_8
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DOI: https://doi.org/10.1007/978-1-4757-3218-4_8
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