The Continued Evolution of the Genetic Code
Abstract
At the time of its elucidation the genetic code was suggested to be universal in all organisms, and the result of a ‘frozen accident’ unable to evolve further even if the current state were suboptimal (1). How do we see the genetic code today – 45 years after the familiar ‘alphabet’ with 20 amino acids was established?
There are 22 natural amino acids (2-4): selenocysteine, the 21st, and pyrrolysine, the 22nd, are directly inserted into growing polypeptides during translation. Selenocysteine is synthesized via a tRNA-dependent pathway and decodes UGA codons (5-7). The incorporation of selenocysteine requires the concerted action of specific RNA and protein elements. In contrast, pyrrolysine is ligated directly to a suppressor tRNAPyl and inserted into proteins in response to UAG codons without a complex re-coding machinery (8-11).
Based on the realization that protein plasticity is a feature of living cells (12), man-made expansion of the genetic code has begun by adding non-standard amino acids to the repertoire of the cell (13, 14). These present evolutionary developments are the underpinning for the creation of new organisms in the realm of synthetic biology.References
2. Ambrogelly, A., Palioura, S. & Söll, D. (2007) Natural expansion of the genetic code. Nat. Chem. Biol. 3, 29.
3. Sheppard, K., Yuan, J., Hohn, M., Jester, B., Devine, K.M. & Söll, D. (2008) From one amino acid to another: tRNA-dependent amino acid biosynthesis. Nucl. Acids Res. 36, 1813.
4. Yuan, J., O'Donoghue, P., Ambrogelly, A., Gundllapalli, S., Sherrer, R.L., Palioura, S., Simonovic, M. & Söll, D. (2010) Distinct genetic code expansion strategies for selenocysteine and pyrrolysine are reflected in different aminoacyl-tRNA formation systems. FEBS Lett. 584, 342.
5. Yuan, J., Palioura, S., Salazar, J. C., Su, D., O'Donoghue, P., Hohn, M. J., Cardoso, A. M., Whitman, W. B. & Söll, D. (2006) RNA-dependent conversion of phosphoserine forms selenocysteine in eukaryotes and archaea. Proc. Natl. Acad. Sci. USA 103, 18923.
6. Araiso, Y., Sherrer, R.L., Ishitani, R., Ho, J.M.L., Söll, D. & Nureki, O. (2009) Structure of a tRNA-dependent kinase essential for selenocysteine decoding. Proc. Natl. Acad. Sci. USA 106, 16215.
7. Palioura, S., Sherrer, R.L., Steitz, T.A., Söll, D. & Simonovic, M. (2009) Catalytic complex of human SepSecS-tRNASec reveals mechanism of selenocysteine formation. Science 325, 321.
8. Polycarpo, C., Ambrogelly, A., Bérubé, A., Winbush, S.M., McCloskey, J.A., Crain, P.F., Wood, J.L. & Söll, D. (2004) An aminoacyl-tRNA synthetase that specifically activates pyrrolysine. Proc. Natl. Acad. Sci. USA 101, 12450.
9. Kavran, J.M., Gundllapalli, S., O'Donoghue, P., Englert, M., Söll, D. & Steitz, T.A. (2007) The structure of pyrrolysyl-tRNA synthetase: an archaeal enzyme for genetic code innovation. Proc. Natl. Acad. Sci. USA 104, 11268.
10. Nozawa, K., O'Donoghue, P., Gundllapalli, S., Araiso, Y., Ishitani, R., Umehara, T., Söll, D. & Nureki, O. (2009) Pyrrolysyl-tRNA synthetase–tRNAPyl structure reveals the molecular basis of orthogonality. Nature 457, 1163.
11. Heinemann, I.U., O'Donoghue, P., Madinger, C., Benner, J., Randau, L., Noren, C.J. & Söll, D. (2009) The appearance of pyrrolysine in tRNAHis guanylyltransferase by neutral evolution. Proc. Natl. Acad. Sci. USA 106, 21103.
12. Ruan, B., Palioura, S., Sabina, J., Marvin-Guy, L., Kochhar, S., LaRossa, R. & Söll, D. (2008) Quality control despite mistranslation caused by an ambiguous genetic code. Proc. Natl. Acad. Sci. USA 105, 16502.
13. Liu, C.C. and Schultz, P.G. (2010) Adding new chemistries to the genetic code. Annu Rev Biochem, 79, 413.
14. Park, H-S., Hohn, M.J., Umehara, T., Guo, L-T., Osborne, E.M., Benner, J., Noren, C.J., Rinehart, J. & Söll, D. (2011) Expanding the genetic code of Escherichia coli with phosphoserine. Science, in press.
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