[
2006]
To date, Smad family members have been found only in eumetazoan animals. To understand the evolutionary relationship between family members we conducted a phylogenetic analysis. To simplify the analysis but retain its explanatory power, we focused on Smad proteins from organisms in three distinct phyla: human, fly, and nematode. Overall, we found that human and fly proteins always cluster together in four subfamilies while three subfamilies contain only nematode proteins. Sequence alignments of distinct regions of were also analyzed. Data from the alignments confirmed that the MH1 (DNA-binding) and MH2 (protein-protein interaction) domains are highly conserved family-wide. The linker region between these domains is also highly conserved but only within subfamilies. Conservation in the C-terminal receptor phosphorylation region provides new insight into a unique subfamily containing three interacting nematode proteins that signal for DAF-7. From a larger perspective, our analysis strongly supports the traditional view that flies are more closely related to humans than to nematodes.