The Robustness and Evolvability of Transcription Factor Binding Sites

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Science  21 Feb 2014:
Vol. 343, Issue 6173, pp. 875-877
DOI: 10.1126/science.1249046

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Robust to Change

The variation in genetic sequences determining the binding of transcription factors is believed to be an important facet of evolution. However, the degree to which a genome is robust, that is, able to withstand changes and how robustness affects evolution is unclear. Payne and Wagner (p. 875) investigated the empirical support for mutational robustness by examining transcription factor (TF) binding in the mouse and yeast genomes. A network analysis of the degree of variation revealed that the sites with the highest affinity for TF binding exhibit the greatest tolerance for nucleotide substitutions, whereas low-affinity sites exhibit greater sensitivity to mutation. Thus, while mutational robustness and evolvability are antagonistic at the genotypic level, they are synergistic at the phenotypic level.


Robustness, the maintenance of a character in the presence of genetic change, can help preserve adaptive traits but also may hinder evolvability, the ability to bring forth novel adaptations. We used genotype networks to analyze the binding site repertoires of 193 transcription factors from mice and yeast, providing empirical evidence that robustness and evolvability need not be conflicting properties. Network vertices represent binding sites where two sites are connected if they differ in a single nucleotide. We show that the binding sites of larger genotype networks are not only more robust, but the sequences adjacent to such networks can also bind more transcription factors, thus demonstrating that robustness can facilitate evolvability.

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