Abstract
Using novel advances in computational chemistry, we demonstrate that the set of 20 genetically encoded amino acids, used nearly universally to construct all coded terrestrial proteins, has been highly influenced by natural selection. We defined an adaptive set of amino acids as one whose members thoroughly cover relevant physico-chemical properties, or “chemistry space.” Using this metric, we compared the encoded amino acid alphabet to random sets of amino acids. These random sets were drawn from a computationally generated compound library containing 1913 alternative amino acids that lie within the molecular weight range of the encoded amino acids. Sets that cover chemistry space better than the genetically encoded alphabet are extremely rare and energetically costly. Further analysis of more adaptive sets reveals common features and anomalies, and we explore their implications for synthetic biology. We present these computations as evidence that the set of 20 amino acids found within the standard genetic code is the result of considerable natural selection. The amino acids used for constructing coded proteins may represent a largely global optimum, such that any aqueous biochemistry would use a very similar set.
Highlights
Using novel advances in computational chemistry, we demonstrate that the set of 20 genetically encoded amino acids, used nearly universally to construct all coded terrestrial proteins, has been highly influenced by natural selection
We present these computations as evidence that the set of 20 amino acids found within the standard genetic code is the result of considerable natural selection
Previous analyses considered a total of at most 76 amino acids: 50 that had been identified in the Murchison meteorite the 12 remaining encoded amino acids not found in Murchison, and 14 intermediates of the metabolic pathways by which contemporary organisms synthesize amino acids
Summary
Using novel advances in computational chemistry, we demonstrate that the set of 20 genetically encoded amino acids, used nearly universally to construct all coded terrestrial proteins, has been highly influenced by natural selection. Even assuming life’s usage of amino acids was biased by plausible prebiotic sources, of which a plethora exist, it appears that at least half of the genetically encoded amino acids arose as ‘‘inventions’’ of early living systems - novel chemical derivations of simpler counterparts during early metabolic evolution[5] Combined, these two insights suggest that the set of amino acids incorporated into genetic coding represents only a small fraction of the wider pool of alternatives that might plausibly have been used[6,7]. Recent work that applied chemoinformatics and structure generation to the question of the isomer space surrounding the genetically encoded amino acids indicates far more possibilities than previously imagined, numbering (depending on the structure generation criteria) in the range of several thousands to a few billion[11] This finding calls into www.nature.com/scientificreports question the robustness of evidence regarding the adaptive qualities of the encoded amino acids relative to a background pool of only 76 alternatives. We begin to explore for the first time some ‘‘better sets,’’ which, given their adaptive qualities, might be plausible candidates for alternative biochemistries
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