Coevolution of HMG domains and homeodomains and the generation of transcriptional regulation by Sox/POU complexes

The highly conserved homeodomains and HMG domains are components of a large number of proteins that play a role in the transcriptional regulation of g ene expression during embryogenesis. Both the HMG domain and the homeodomai n serve as interfaces for factor interactions with DNA, as well as with oth er proteins, and it is likely that the high degree of structural and sequen ce conservation within these domains reflects the conservation of basic asp ects of these interactions. Classical HMG domain proteins have an ancient o rigin, being found in all eukaryotes, and are thought to have given rise to the metazoan-specific class of HMG domain proteins called the Sox proteins . Similarly, the metazoan-specific POU domain proteins are thought to have arisen from genes encoding ancestral homeodomain proteins. In this review, we summarize several examples of different HMG-homeodomain interactions tha t illustrate not only the ancient origin of each of these protein families, but also their relationship to each other, and discuss how coevolution of HMG and homeodomains may have lead to creation of the specialized Sox/POU p rotein complexes. Using the FGF-4 gene as an example, we also speculate on how coevolution of regulatory Sox/POU target DNA sequences may have occurre d, and how the summation of these changes may have lead to the emergence of new developmental pathways. (C) 2001 Wiley-Liss, Inc.