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

146 Citations (Scopus)

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 1999

Fingerprint

Molecular Evolution
Transforming Growth Factors
Transducers
Ligands
Multigene Family
Activins
Growth Factor Receptors
Arthropods
Caenorhabditis elegans
Prednisolone
Serine
Drosophila
Mammals
Signal Transduction
Fungi
History
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Molecular evolution of a developmental pathway : Phylogenetic analyses of transforming growth factor-β family ligands, receptors and Smad signal transducers. / Newfeld, Stuart; Wisotzkey, Robert G.; Kumar, Sudhir.

In: Genetics, Vol. 152, No. 2, 06.1999, p. 783-795.

Research output: Contribution to journalArticle

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