Analysis of a complete DNA-protein affinity landscape

J R Soc Interface. 2010 Mar 6;7(44):397-408. doi: 10.1098/rsif.2009.0193. Epub 2009 Jul 22.


Properties of biological fitness landscapes are of interest to a wide sector of the life sciences, from ecology to genetics to synthetic biology. For biomolecular fitness landscapes, the information we currently possess comes primarily from two sources: sparse samples obtained from directed evolution experiments; and more fine-grained but less authentic information from 'in silico' models (such as NK-landscapes). Here we present the entire protein-binding profile of all variants of a nucleic acid oligomer 10 bases in length, which we have obtained experimentally by a series of highly parallel on-chip assays. The resulting complete landscape of sequence-binding pairs, comprising more than one million binding measurements in duplicate, has been analysed statistically using a number of metrics commonly applied to synthetic landscapes. These metrics show that the landscape is rugged, with many local optima, and that this arises from a combination of experimental variation and the natural structural properties of the oligonucleotides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological / genetics
  • Aptamers, Nucleotide / metabolism*
  • Computational Biology
  • DNA-Binding Proteins / metabolism*
  • Evolution, Molecular
  • Models, Genetic
  • Phycocyanin / chemistry
  • Phycocyanin / genetics
  • Phycocyanin / metabolism*


  • Aptamers, Nucleotide
  • DNA-Binding Proteins
  • allophycocyanin
  • Phycocyanin