Abstract: The present invention relates to the field of evolution of nucleic acids in vivo and provides methods and compositions for introducing diversity into gene products. The present invention allows generation of new sequences that have desirable properties by virtue of high frequency mutation events within a cell. The high frequency mutation of a polynucleotide sequence results in, the production of a large population of new sequence variants. Appropriate selection and/or screening permits identification and isolation of mutant forms of the polynucleotide sequence as well as products resulting from expression of the mutant sequences.