On the conservative nature of intragenic recombination

  • Drummond D
  • Silberg J
  • Meyer M
 et al. 
  • 122

    Readers

    Mendeley users who have this article in their library.
  • 66

    Citations

    Citations of this article.

Abstract

Intragenic recombination rapidly creates protein sequence diversity compared with random mutation, but little is known about the relative effects of recombination and mutation on protein function. Here, we compare recombination of the distantly related beta-lactamases PSE-4 and TEM-1 to mutation of PSE-4. We show that, among beta-lactamase variants containing the same number of amino acid substitutions, variants created by recombination retain function with a significantly higher probability than those generated by random mutagenesis. We present a simple model that accurately captures the differing effects of mutation and recombination in real and simulated proteins with only four parameters: (i) the amino acid sequence distance between parents, (ii) the number of substitutions, (iii) the average probability that random substitutions will preserve function, and (iv) the average probability that substitutions generated by recombination will preserve function. Our results expose a fundamental functional enrichment in regions of protein sequence space accessible by recombination and provide a framework for evaluating whether the relative rates of mutation and recombination observed in nature reflect the underlying imbalance in their effects on protein function.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • D. A. Drummond

  • J. J. Silberg

  • M. M. Meyer

  • C. O. Wilke

  • F. H. Arnold

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free