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

Stuart Newfeld, Robert G. Wisotzkey, Sudhir Kumar

Research output: Contribution to journalArticle

150 Scopus citations

Abstract

Intercellular signaling by transforming growth factor-β (TGF-β) proteins coordinates developmental decisions in many organisms. A receptor complex and Smad signal transducers are required for proper responses to TGF- β signals. We have taken a phylogenetic approach to understanding the developmental evolutionary history of TGF-β signaling pathways. We were interested in detecting evolutionary influences among the physically interacting multigene families encoding TGF-β 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 (I) TGF-β pathways do not predate the divergence of animals, plants, and fungi; (2) ligands of the TGF-β/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-β signal transduction. We discuss these findings with respect to the coevolution of physically interacting genes.

Original languageEnglish (US)
Pages (from-to)783-795
Number of pages13
JournalGenetics
Volume152
Issue number2
StatePublished - Jun 1 1999

ASJC Scopus subject areas

  • Genetics

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