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Stephen Freeland
University of Hawaii, Manoa


Stephen Freeland researches the origin and evolution of genetic coding.

The evolution of genetic coding – i.e. the synthesis of proteins according to genetic instructions – was a momentous breakthrough for life on our planet. It connected the information storage and transmission potential of polymerized nucleotide sequences (DNA and RNA) to the structural and catalytic properties of polymerized amino acid sequences (proteins). This created a biochemical framework of such flexibility that billions of years of subsequent evolution have not improved upon it, despite the fact that life has evolved such diversity that modern biology is challenged to find the limits for cellular life.
The universal features of life’s biochemistry extend far beyond any general principle of connecting these two bio-polymers. In discovering the molecular interface by which living systems translate specific triplet nucleotide code-words of genetic information (codons) into specific amino acids, researchers were surprised to find the same exact genetic code at work in bacteria and humans. Although subsequent research has uncovered lineages using slight variations in their genetic codes (including some that have added one of two extra amino acids), it seems clear that one standard genetic code had evolved by the time of the Last Universal Common Ancestor of present day life (LUCA). Freeland’s particular focus is on finding the exploring the relative roles of chance and determinism in the emergence of this standard genetic code. In particular, he has helped to develop evidence that the distribution of genetic code-words (codons) to encoded meanings (amino acids) is decidely non-random: it appears to minimize the average impact of random errors (mutations and misreadings) by maximizing the bochemical similarity of amino acids assigned to similar codons. More recently he has focussed on evolution’s “choice” of amino acids from a far larger pool of candidates available to the origin and early evolution of life.

Selected Publications

Peer Reviewed Publications * (2011) “Did evolution select a non-random “alphabet” of amino acids?” Philip G and Freeland SJ, Astrobiology 11 * (2008) “A quantitative investigation of the chemical space surrounding amino acid alphabet formation.” Lu Y and Freeland SJ, J Theor Biol. 250:349-61. * (2008) “Optimal encoding rules for synthetic genes: the need for a community effort.” Wu G, Dress L, Freeland S.J., Mol Syst Biol. 3:134 * (2007) “Amino Acid Quantitative Structure Property Relationship Database: a web-based platform for quantitative investigations of amino acids.” Y. Lu and S.J. Freeland, Protein Eng Des Sel. 7:347-51. * (2007) “The effects of differential gene expression on coding sequence features: Analysis by one-way ANOVA.” G. Wu, L. Nie and S. J. Freeland, Biochem Biophys Res Commun.; 358(4):1108-13. * (2007) “SGDB: A database of synthetic genes re-designed for optimizing protein over-expression.” G. Wu, Y. Zheng, I. Qureshi, H.T. Zin, T. Beck, B. Bulka, and S.J. Freeland, Nucleic Acids Research 35(Database issue):D76-9 * (2006) “On the evolution of the standard amino-acid alphabet.” Y. Lu and S.J. Freeland. Genome Biology, 7:102 * (2006) “An Interactive Visualization Tool to Explore the Biophysical Properties of Amino Acids and Their Contribution to Substitution Matrices.” B. Bulka, M. desJardins and S.J. Freeland, BMC Bioinformatics, 7:329. * (2006) “Testing the Potential for Computational Chemistry to Quantify Physiochemical Properties of the Non-Proteinaceous Amino Acids.” Y. Lu and S.J. Freeland, Astrobiology. 6: 606-624. * (2006) “Simplified Gene Synthesis: A one-step approach to PCR-based gene construction.” G. Wu, J.B. Wolf, A.F. Ibrahim, S. Vadasz, M. Gunasinghe, and S.J. Freeland, J. of Biotechnology, 124: 496-503 * (2006) “The standard genetic code enhances adaptive evolution of proteins”. W. Zhu and S.J. Freeland, Journal of Theoretical Biology, 239: 63-70. * (2005) “The Synthetic Gene Designer: A flexible web platform to explore sequence manipulation for heterologous expression.” G. Wu, N. Bashir-Bello, and S.J. Freeland. Protein Expression and Purification, 47: 441-5. * (2004) “Evolution Encoded” S.J. Freeland and L. Hurst, Scientific American, 290:84-91. * (2003) “The case for an Error Minimizing Standard Genetic Code.” S.J. Freeland, T. Wu and N. Keulmann, Origins of Life and Evolution of the Biosphere, 33: 457-477. Stephen J. Freeland * (2002) “The Darwinian genetic code: An adaptation for adapting?” S.J. Freeland. Journal of Genetic Programming and Evolvable Machines, 3: 113-127.(acm digital library) * (2001) “A simple model based on mutation and selection explains trends in codon and amino-acid usage and GC composition within and across genomes.” R.D. Knight, S.J. Freeland and L.F. Landweber, Genome Biology 2(4):RESEARCH0010 * (2001) “Testing a biosynthetic theory of genetic code evolution: fact or artefact?” T.A. Ronneberg, L.F. Landweber and S.J. Freeland, Proc. Natl. Acad. Sci. USA, 97(25):13690-5 * (2001) “Rewiring the keyboard: evolvability of the genetic code” R.D. Knight, S. J. Freeland and L. F. Landweber, Nature Reviews Genetics, 2(1):49-58. PDF * (2000) “Early Fixation of an Optimal Genetic Code.” S.J. Freeland, R.D. Knight, L.F. Landweber and L.D. Hurst. Molecular Biology and Evolution ,17 pp. 511-518. * (2000) “Measuring adaptation within the genetic code.” S.J. Freeland, R.D. Knight and L.F. Landweber, Trends in the Biochemical Sciences, 25 pp. 44-45. PDF * (1999) “The 3 Faces of the Genetic Code.” R.D. Knight, S. J. Freeland and L. F. Landweber, Trends in the Biochemical Sciences. 282(24), pp. 241-247 PDF * (1999) “Do Proteins Predate DNA?” S.J. Freeland, R.D. Knight, L.F. Landweber, Science, 286, pp. 690-2 HTML * (1998) Load minimisation of the genetic code: History does not explain the pattern. S.J. Freeland and L.D. Hurst, Proc. Roy. Soc. Lond. Series B, 265, pp 2111-2119. (Proceedings online) * (1998) The genetic code is one in a million. S.J. Freeland and L.D. Hurst, Journal of Molecular Evolution, 47(3), pp. 238-248

Books and Book Chapters * (2009) “'Terrestrial’ Amino Acids and their evolution”. S.J. Feeland in Amino Acids, Peptides and Proteins within Organic Chemistry, Vol. 1 (ed. A. B. Hughes), Wiley VCH. (Wiley press) * (2007) Fitness of the Cosmos for Life, eds. J. Barrow, S. Conway-Morris and S.J. Freeland , Cambridge University Press, ISBN-10: 0521871026 (Cambridge University Press) * (2007) “Could an intelligent alien predict earth’s biochemistry?” S.J. Freeland in Fitness of the Cosmos for Life, eds. J. Barrow, S. Conway-Morris and S.J. Freeland), Cambridge University Press. * (2003) “Three Fundamentals of the Biological Genetic Algorithm”. S.J. Freeland in Genetic Programming Theory and Practice (eds. R. Riolo and B. Worzel, Kluwer Academic.(

NAI Project Collaborators

Past NAI Teams