Abstract: The invention provides a method for generating a polynucleotide sequence or population of sequences from parent polynucleotide sequences, the method comprising the steps of (a) providing a population of parent polynucleotide molecules, which population comprises plus and minus strands, (b) treating the population of parent polynucleotide molecules to generate a population of polynucleotide fragments thereof, (c) incubating the population of polynucleotide fragments under conditions which permit the formation of overlapping fragment pairs and (d) amplifying the overlapping fragment pairs using a polymerase to generate one or more product polynucleotide molecules which differ in sequence from the parent polynucleotide molecules, wherein step (d) is performed, at least in part, under conditions which favor the introduction of mutations into the one or more product polynucleotide molecules.