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MBE Advance Access published online on April 25, 2003

Molecular Biology and Evolution, doi:10.1093/molbev/msg096
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2003; all rights reserved
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Accepted January 24, 2003
© 2003 Society for Molecular Biology and Evolution

Original Articles

The Effects of Selection against Spurious Transcription Factor Binding Sites

Matthew W. Hahn 1*, Jason E. Stajich 1, Gregory A. Wray 1

1 Department of Biology, Duke University

* To whom correspondence should be addressed. E-mail: mwh3{at}duke.edu.


   Abstract

Most genomes contain nucleotide sequences with no known function; such sequences are assumed to be free from constraints, evolving only according to the vagaries of mutation. Here we show that selection acts to remove spurious transcription factor binding site motifs throughout 52 fully-sequenced genomes of Eubacteria and Archaea. Examining the sequences necessary for polymerase binding, we find that spurious binding sites are under-represented in both coding and non-coding regions. The average proportion of spurious binding sites found relative to the expected is 80% in eubacterial genomes and 89% in archaeal genomes. We also estimate the strength of selection against spurious binding sites in the face of the constant creation of new binding sites via mutation. Under conservative assumptions we estimate that selection is weak, with the average efficacy of selection against spurious binding sites, Nes, of -0.12 for eubacterial genomes and -0.06 for archaeal genomes, similar to that of codon bias. Our results suggest that both coding and non-coding sequences are constrained by selection to avoid specific regions of sequence space.

Key Words: Comparative genomics, natural selection, motif bias, promoters


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