On the conservative nature of intragenic

Intragenic recombination rapidly creates protein sequence diver-sitycomparedwithrandommutation,butlittleisknownabouttherelative effects of recombination and mutation on protein func-tion. Here, we compare recombination of the distantly related -lactamasesPSE-4andTEM-1tomutationofPSE-4.Weshowthat,among -lactamasevariantscontainingthesamenumberofaminoacid substitutions, variants created by recombination retain func-tion with a significantly higher probability than those generatedby random mutagenesis. We present a simple model that accu-ratelycapturesthedifferingeffectsofmutationandrecombinationin real and simulated proteins with only four parameters: (