There is provided a method for evolving an orthogonal rRNA molecule, comprising the steps of: providing one or more libraries of mutant orthogonal rRNA molecules and introducing the libraries into cells such that the orthogonal rRNA is incorporated into ribosomes to provide orthogonal ribosomes providing one or more orthogonal mRNA molecules which (i) are not translated by natural ribosomes, and (ii) comprise one or more orthogonal mRNA codons assaying the translation of the orthogonal mRNA and selecting the orthogonal rRNA molecules which translate the orthogonal mRNA, wherein the assay in step (c) requires translation of one or more orthogonal mRNA codons in the orthogonal mRNA and orthogonal ribosomes incorporating such rRNA molecules.
