Testing for adaptive signatures of amino acid alphabet evolution using chemistry space

Abstract

Background: Multidisciplinary consensus indicates that half of the genetically amino acids are likely to have been available on the prebiotic earth, which implies certain adaptive expectations for the relationship between those amino acids and later additions to the genetic code. Chemistry space a concept that translates molecules to corresponding points in multidimensional space provides a framework for investigating these relationships. We therefore developed three tests to explore these implications using chemistry space to quantify otherwise qualitative questions. Results: All three of our tests individually, as well as combined, provide quantitative evidence to support an adaptive expansion of the genetically encoded amino acid alphabet from 10 prebiotically plausible ("early") amino acids to the full set of 20 amino acids found within the standard genetic code. Conclusions: We present three logically independent, novel tests of the adaptive growth of the amino acid alphabet from a smaller, functionally cohesive alphabet of only 10 amino acids to the 20 amino acids of the standard genetic code. While similar tests in the past have compared the genetically encoded amino acids to an external context of amino acids that were not incorporated into the genetic code our tests focus on the internal context of the 20 genetically encoded amino acids and find strong support. Of particular note one of these tests for the first time moves beyond consideration of amino acids as monomers and begins to explore polypeptides by considering the chemistry space of amino acid dimers.