Analysis of a complete DNA-protein affinity landscape.
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.
Rowe
William
W
Manchester Interdisciplinary Biocentre, University of Manchester , 131 Princess Street, Manchester M1 7DN, UK. william.rowe@manchester.ac.uk
Platt
Mark
M
Wedge
David C
DC
Day
Philip J
PJ
Kell
Douglas B
DB
Knowles
Joshua
J
D000220:Adaptation, Biological / Q000235:genetics; D052157:Aptamers, Nucleotide / Q000378:metabolism*; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019143:Evolution, Molecular; D008957:Models, Genetic; D010798:Phycocyanin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D052157:Aptamers, Nucleotide; D004268:DNA-Binding Proteins; C002497:allophycocyanin; D010798:Phycocyanin