The essential unity of the Code across organisms suggests that it was in place in its current form at or before the last universal common ancestor (LUCA)

Woese has suggested that primitive organisms with different but flexible codes engaged in horizontal gene transfer to arrive at a common Code.

• What variations do exist suggest that the Code evolved

• Similar codons for similar amino acids suggest evolution to minimize impact of errors

• But how did the codons become what they are?

Several mechanisms have been proposed, all of which trace the Code back to RNA World

One suggestion:

• Amino acids were bound by their codons or anticodons

• Ribozymes bound the codons and carried out ligation

• Some evidence:
  Riboswitches, small segments of mRNAs that regulate translation of mRNA, bind small molecules; for example, the Met riboswitch binds S-adenosylmethionine (SAM)

  SAM Bound by Riboswitch	SAM Surrounded by A, U, and G, the Met codon

  • Amino acid components of the proteins in the ribosome lie near their codons or anticodons

  • Small RNAs evolved in vitro to bind amino acids tend to contain codons or anticodons

Another possibility is that small nucleotides with amino acids covalently attached were the original units of replication.

• These units would bind to larger RNAs (which later evolved into the ribosome)

• A loop of the larger RNA evolved the ability to catalyze peptide bond formation

• The bases at the binding sites of these units became the codons.

• Chemical transformations of simple amino acids bound to nucleotides led to the more complex amino acids, which captured codons from their precursors

• The nucleotides of these units evolved into tRNA

• A number of amino acids still are synthesized from others while attached t tRNA
  • For example, selenocysteine from serine on tRNA^Ser, glutamine from glutamic acid on tRNA^Gln, and asparagine from aspartic acid on tRNA^Asn

• Ribozymes bind abiogenic amino acids that enhance their reactivity

• These ribozymes evolve to catalyze peptide ligation; thus we have the precursor of the large ribosomal subunit

• Others of the amino acid binding ribozymes evolve into self-charging proto-tRNAs, selected for accumulation and delivery of amino acids to the ligase

• A loop of the ligase ribozyme evolves into an RNA structure that binds the proto-tRNAs, becoming the precursor of the small ribosomal subunit
  • This is where the code develops

• This proto-ribosome can synthesize small peptides

• Evolution of translocation of the peptides leads to longer peptides

While we cannot go back to the RNA World to test these ideas, test-tube evolution of nucleic acid structures is possible by the SELEX technique:

Using SELEX various groups have evolved:

• A self-aminoacylating ribozyme, using Phe-AMP as a substrate

• Ribozymes that can make dipeptides

  Ribozymes that can extend an RNA primer by 10-14 nucleotides

Read more:

Stevenson, J. Theor. Biol., 2002, 217, 235

Klipcan and Safro, J. Theor. Biol., 2004, 228, 389

Wong, BioEssays, 2005, 27, 416

Vetsigian, Woese, and Goldenfeld, Proc. Nat. Acad. Sci., 2006, 103, 10696

Wolf and Koonin, Biol. Direct, 2007, 2, 14

Yarus, Widman, and Knight, J. Mol. Evol., 2009, 69, 406