Evolutionary selection pressure of forkhead domain and functional divergence.

Forkhead-box (Fox) genes encode a family of transcription factors defined by a "winged helix" DNA-binding domain which have been identified in many metazoans, and play important roles in diverse biological processes. Here we aimed to extend previous evolutionary selection analysis to fungi, using available sequences from E. cuniculi (Ec), Eremothecium gossypii (Eg), Saccharomyces cerevisiae (Sc), etc. The phylogeny of 335 Fox protein sequences was reconstructed, revealing the existence of 26 orthologous groups that were well supported by gene phylogeny which arose following a series of gene duplication events. Gene conversion events may also play important roles in the evolution of Fox genes. The nonsynonymous to synonymous substitution ratios (dN/dS) for orthologous groups suggested that after gene duplication and/or speciation of forkhead clusters, rapid differentiation and the negative selection have occurred, prompting the formation of distinct Fox subclasses and new functions. SDPpred was used to produce a set of the alignment positions (specificity determining positions) which is involved in conferring differential functional specificity. These findings explained the functional divergence of Fox gene family.