Correlated evolutions of transcript factors and their binding sites


The interaction between transcription factors (TFs) and their DNA binding sites (TFBSs) is essential for gene regulation. Mutation in either the TF or the TFBS may weaken the interaction and thus result in abnormalities. To maintain such vital interaction, a mutation in one of the interacting partners might be balanced by a corresponding correlated mutation in its binding partner during the course of evolution. Here we show that for the basic Helix-Loop-Helix (bHLH) family of TFs, the evolution of the TFs and their TFBSs are significantly correlated across vertebrates. We further developed a mutual information based method to identify highly co-evolved protein residues and DNA bases. This research provided the first evidence to show the correlated evolutions of TFs and TFBSs, and shed light on the dynamic relationship between them during evolution. The same strategy can be applied to co-evolutionary studies in other Protein-DNA or Protein-RNA interactions.


Datasets and source codes:
Please find the related files and source code from here .


We thank Profs Terry Hwa, Gary Stormo, Sridhar Hannenhalli and Li-SanWang, the anonymous reviewers and members in the JJWang lab for critical comments on the manuscript.

Funding: The Research Grants Council of Hong Kong (781511M, 778609M, N_HKU752/10, AoE M-04/04); Food and Health Bureau of Hong Kong (10091262); the National Science Foundation of China (31061160497).
Conflict of interest statement. None declared.


*Correspondence should be addressed to Junwen Wang
(Tel: +852 2819 2809; Fax: +852 2855 1254)
(Email: ).
(Office: L3-80, Laboratory Block, 21 Sassoon Road, Hong Kong).


Correlated evolution of transcription factors and their binding sites.
Shu Yang, Hari Krishna Yalamanchili, Xinran Li, Kwok-Ming Yao, Pak Chung Sham, Michael Q. Zhang and Junwen Wang Bioinformatics. (2011) 27 (21): 2972-2978. doi: 10.1093/bioinformatics/btr503