Document Detail

A quantitative investigation of the chemical space surrounding amino acid alphabet formation.
MedLine Citation:
PMID:  18005995     Owner:  NLM     Status:  MEDLINE    
To date, explanations for the origin and emergence of the alphabet of amino acids encoded by the standard genetic code have been largely qualitative and speculative. Here, with the help of computational chemistry, we present the first quantitative exploration of nature's "choices" set against various models for plausible alternatives. Specifically, we consider the chemical space defined by three fundamental biophysical properties (size, charge, and hydrophobicity) to ask whether the amino acids that entered the genetic code exhibit a higher diversity than random samples of similar size drawn from several different definitions of amino acid possibility space. We found that in terms of the properties studied, the full, standard set of 20 biologically encoded amino acids is indeed significantly more diverse than an equivalently sized group drawn at random from the set of plausible, prebiotic alternatives (using the Murchison meteorite as a model for pre-biotic plausibility). However, when the set of possible amino acids is enlarged to include those that are produced by standard biosynthetic pathways (reflecting the widespread idea that many members of the standard alphabet were recruited in this way), then the genetically encoded amino acids can no longer be distinguished as more diverse than a random sample. Finally, if we turn to consider the overlap between biologically encoded amino acids and those that are prebiotically plausible, then we find that the biologically encoded subset are no more diverse as a group than would be expected from a random sample, unless the definition of "random sample" is adjusted to reflect possible prebiotic abundance (again, using the contents of the Murchison meteorite as our estimator). This final result is contingent on the accuracy of our computational estimates for amino acid properties, and prebiotic abundances, and an exploration of the likely effect of errors in our estimation reveals that our results should be treated with caution. We thus present this work as a first step in quantifying and thus testing various origin-of-life hypotheses regarding the origin and evolution of life's amino acid alphabet, and advocate the progress that would add valuable information in the future.
Yi Lu; Stephen J Freeland
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-12
Journal Detail:
Title:  Journal of theoretical biology     Volume:  250     ISSN:  1095-8541     ISO Abbreviation:  J. Theor. Biol.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-25     Completed Date:  2008-04-11     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0376342     Medline TA:  J Theor Biol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  349-61     Citation Subset:  IM    
Department of Biological Sciences, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 25250, USA.
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MeSH Terms
Amino Acids / biosynthesis,  chemistry*,  genetics
Computational Biology / methods
Evolution, Molecular*
Genetic Variation
Models, Chemical
Models, Genetic*
Reg. No./Substance:
0/Amino Acids

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