Molecular evolution of a developmental pathway: Phylogenetic analyses of transforming growth factor-beta family ligands, receptors and Smad signal transducers

Intercellular signaling by transforming growth factor-beta (TGF-beta) prote ins coordinates developmental decisions in many organisms. A receptor compl ex and Smad signal transducers are required for proper responses to TGF-bet a signals. We have taken a phylogenetic approach to understanding the devel opmental evolutionary history of TGF-beta signaling pathways. We were inter ested in detecting evolutionary influences among the physically interacting multigene families encoding TGF-beta ligands, receptors, and Smads. Our an alyses included new ligands and Smads identified from genomic sequence as w ell as the newest published family members. From an evolutionary perspectiv e we find that (1) TGF-beta pathways do not predate the divergence of anima ls, plants, and fungi; (2) ligands of the TGF-beta/activin subfamily likely originated after the divergence of nematodes and arthropods; (3) type I re ceptors from Caenorhabditis elegans are distinct from other receptors and m ay reflect an ancestral transitional state between type I and type II recep tors; and (4) the Smad family appears to he evolving faster than, and indep endently of ligands and receptor From a developmental perspective we find ( 1) numerous phylogenetic associations not previously detected in each multi gene family; (2) that there are unidentified pathway components that discri minate 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-te rminal serines is the best predictor of a Smad's role in TGF-beta signal tr ansduction. We discuss these findings with respect to the coevolution of ph ysically interacting genes.