Molecular Evolution of a Developmental Pathway: Phylogenetic Analyses of Transforming Growth Factor-ß Family Ligands, Receptors and Smad Signal Transducers

Corresponding author: Stuart J. Newfeld, Department of Biology, Arizona State University, Tempe, AZ 85287-1501., newfeld{at}asu.edu (E-mail)

Communicating editor: A. G. CLARK

Intercellular signaling by transforming growth factor-ß (TGF-ß) proteins coordinates developmental decisions in many organisms. A receptor complex and Smad signal transducers are required for proper responses to TGF-ß signals. We have taken a phylogenetic approach to understanding the developmental evolutionary history of TGF-ß signaling pathways. We were interested in detecting evolutionary influences among the physically interacting multigene families encoding TGF-ß ligands, receptors, and Smads. Our analyses included new ligands and Smads identified from genomic sequence as well as the newest published family members. From an evolutionary perspective we find that (1) TGF-ß pathways do not predate the divergence of animals, plants, and fungi; (2) ligands of the TGF-ß/activin subfamily likely originated after the divergence of nematodes and arthropods; (3) type I receptors from Caenorhabditis elegans are distinct from other receptors and may reflect an ancestral transitional state between type I and type II receptors; and (4) the Smad family appears to be evolving faster than, and independently of, ligands and receptors. From a developmental perspective we find (1) numerous phylogenetic associations not previously detected in each multigene family; (2) that there are unidentified pathway components that discriminate between type I and type II receptors; (3) that there are more Smads to be discovered in Drosophila and mammals; and (4) that the number of C-terminal serines is the best predictor of a Smad's role in TGF-ß signal transduction. We discuss these findings with respect to the coevolution of physically interacting genes.

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