Science and Engineering

University of North Carolina at Chapel Hill

Charles Carter, Abigail Knight, Qi Zhang, Hiroaki Suga
Chapel Hill, NC
$1,000,000
December 2020
 

Life requires intimate coordination of two different kinds of polymers.  Nucleic acids carry genetic information as genes, which are the blueprints for making specific proteins.  Proteins, the poly-amino acids assembled according to the genetic code, have vastly more diverse and complex functionality.  Replication of genes—the basis of life’s memory—requires a coded protein enzyme, suggesting that replication and genetic coding emerged together by some unknown cooperative process.  Details of that process pose an outstanding challenge and paradox associated with unraveling the origin of life.  Reflexivity—enzymes that translate the genetic code must, themselves, enforce the coding rules by which they were assembled—confounds that puzzle.  The remoteness of life’s origins complicates the design of experiments to reveal how genetic coding of peptide sequences could have arisen from simple components.  The UNC team hypothesize that solving this classic “chicken and egg” problem implies the existence of historical context: all successive versions of the code were interpreted by a pre-existing machinery: an “egg laid by a bird that was not a chicken.”  They will investigate a novel hypothesis about that primordial translational machinery by showing that templating of anticodons in the tRNA acceptor stem by nucleic acid sequences containing sequential triplet codons equivalent to those in contemporary protein synthesis, may have sufficed by itself to accelerate peptide synthesis without any other catalyst, while creating a selective advantage for a protoribosomal catalyst.  That experimental translatomics platform facilitates posing testable questions in a uniquely plausible context.  The team will use the platform to investigate the combinatorial chemistry underlying genetic coding by measuring rates and specificities of dipeptide synthesis.  They will further seek a heretofore unknown connection between coding and catalysis by testing whether extant protoribosomal machinery, which appears not to enhance peptide bond formation, can do so if the two adaptors are templated.  The researchers aim to be first to address a crucial step in the transition from random, spontaneous chemistry into the highly organized computational networks characteristic of biological information transfer, reshaping our understanding of how life evolved on earth.

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