Simultaneous codon usage, the origin of the proteome, and the emergence of de-novo proteins.

Genetic coding generally uses only one of a gene's two strands; its complement serving as template for replication. Aminoacyl-tRNA synthetases, aaRS, apparently first emerged as pairs on bidirectional genes, in which anticodons in the template strand served as codons for an entirely different protein. Interpreting both strands in frame constrained such genes sufficiently that it was rapidly superseded, leaving only traces in the elevated pairing between codon middle bases in antiparallel alignments. Codon assignments actually promote using information from both strands in multiple reading frames. Related phenomena, known as overprinting, are widely associated with viruses. In-frame bidirectional coding and overprinting nevertheless imply different structural and functional relationships, and different roles in generating folded proteins throughout the evolution of the proteome.