@article {Qian041145, author = {Long Qian and Edo Kussell}, title = {Natural selection driven by DNA binding proteins shapes genome-wide motif statistics}, elocation-id = {041145}, year = {2016}, doi = {10.1101/041145}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Ectopic DNA binding by transcription factors and other DNA binding proteins can be detrimental to cellular functions and ultimately to organismal fitness. The frequency of protein-DNA binding at non-functional sites depends on the global composition of a genome with respect to all possible short motifs, or k-mer words. To determine whether weak yet ubiquitous protein-DNA interactions could exert significant evolutionary pressures on genomes, we correlate in vitro measurements of binding strengths on all 8-mer words from a large collection of transcription factors, in several different species, against their relative genomic frequencies. Our analysis reveals a clear signal of purifying selection to reduce the large number of weak binding sites genome-wide. This evolutionary process, which we call global selection, has a detectable hallmark in that similar words experience similar evolutionary pressure, a consequence of the biophysics of protein-DNA binding. By analyzing a large collection of genomes, we show that global selection exists in all domains of life, and operates through tiny selective steps, maintaining genomic binding landscapes over long evolutionary timescales.}, URL = {https://www.biorxiv.org/content/early/2016/02/23/041145}, eprint = {https://www.biorxiv.org/content/early/2016/02/23/041145.full.pdf}, journal = {bioRxiv} }