**1.1. Alternative coding by expanded codons**

Switching between regular and stopless genetic codes is not the only strategy increasing dramatically information encoded by genomes. Isolated tetracodons, codons expanded by a fourth silent nucleotide, are known since the dawn of molecular biology [29]. These are sometimes translated by tRNAs with expanded anticodons [30, 31]. It seems probable that systematic frameshifts produce stretches of tetracodons that code for (yet) undetected peptides ([32–34]). Some evidence suggests that tetracoding occurs especially at high environmental temperatures [35] and is predicted by genetic code optimization [36]: codonanticodon interactions are more stable when four rather than only three base pairs hybridize. Other theoretical considerations suggest that the mitochondrial vertebrate genetic code evolved from a specific subset of 64 tetracodons, the tesserae, chosen on the basis of symmetry principles [37].

Indeed, analyses of mitochondrial mass spectra searching for peptides matching translations assuming tetra- and pentacodons, codons expanded by one or two silent nucleotides, detected numerous tetra- and pentacoded peptides [38–43].
