AMINO ACID ALPHABET (R)EVOLUTION: CHANGING THE MOLECULAR BASIS OF LIFE

Abstract

Life on Earth has evolved to construct metabolism as a network of genetically encoded proteins. Each protein comprises a sequence of amino acids, covalently linked together. Early evolution established a single, standard library of 20 L-?-amino acids with which to build proteins since life’s last universal common ancestor (LUCA). Multiple disciplinary lenses agree, however, that a far greater diversity of amino acid structures was available to life’s origins and early evolution. Amino acids appear readily available to the planetary bodies that comprise our galaxy, have been detected within meteorites, produced by a wide range of conditions for simulating prebiotic chemistry, and have even been theorized to occur within the interstellar medium. Given that a single set has proven capable of building proteins adapted to every imaginable environment for life on Earth for more than 3.5 billion years, they are an attractive, recognized focus of astrobiology research. A decade of this research now supports the idea that the genetically encoded set of 20 amino acids exhibits highly unusual physicochemical properties as a set. The range and evenness with which they cover the chemistry space of possible volume and hydrophobicity is remarkable and non-random. This theory has matured far enough that it is both tractable and useful to now ask the question: if an independent origin of life were to build proteins using amino acids then what structures and functions would we expect, using Earth life as a guide? Here I attempt to shed light on an answer to that question through the intersection of “state-of-the-art” computational and empirical methods. This work begins to uncover whether the fundamental molecular biochemistry of life elsewhere, if using monosubstituted alpha amino acids, looks eerily similar to, or starkly different from, life as we know it here on Earth. Specifically, by (i) using a heuristic search algorithm to search for and analyze alternative amino acid alphabets (ii) designing, synthesizing, and characterizing the world’s first xeno peptides; and (iii) evaluating the reliability of state-of-the-art spectral prediction algorithms for xeno amino acids. The results primarily indicate that certain amino acids are predisposed to forming high physicochemical coverage sets, the one amino acid alphabet used by life is not the only one capable of forming peptide structures, and that current spectral prediction algorithms are insufficient when simulating xeno amino acid spectra. I conclude by identifying and calling for the further development of multiple tractable research directions so as to continue uncovering what alternative biochemistries may look like.