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Background  Nuclear receptors (NRs) are transcription factors which bind small hormones, whose evolutionary history and the presence of different functional surfaces makes them an interesting target for a correlation based analysis.    Results  Correlation analysis of ligand binding domains shows that correlated residue subsets arise from the differences between functional sites in different nuclear receptor subfamilies. For the DNA binding domain, particularly, the analysis shows that the main source of correlation comes from residues that regulate hormone response element specificity, and one of the conserved residue sub-sets arises due to the presence of an unusual sequence for the DNA binding motif known as P-box in nematodes, suggesting the existence of different DBD-DNA specificities in nuclear receptors.    Conclusions  We conclude that DNA specificity and functional surface specialization has independently driven nuclear receptor evolution, and suggest possible binding modes for the class of divergent nuclear receptors in nematodes.

Residue correlation networks in nuclear receptors reflect functional specialization and the formation of the nematode-specific P-box