Journal of Molecular Evolution

, Volume 49, Issue 5, pp 567–582

The Evolution of the MAP Kinase Pathways: Coduplication of Interacting Proteins Leads to New Signaling Cascades

  • Daniel R.  Caffrey
  • Luke A.J.  O'Neill
  • Denis C.  Shields

DOI: 10.1007/PL00006578

Cite this article as:
Caffrey, D., O'Neill, L. & Shields, D. J Mol Evol (1999) 49: 567. doi:10.1007/PL00006578

Abstract.

The MAP-kinase pathways are intracellular signaling modules that are likely to exist in all eukaryotes. We provide an evolutionary model for these signaling pathways by focusing on the gene duplications that have occurred since the divergence of animals from yeast. Construction of evolutionary trees with confidence assessed by bootstrap clearly shows that the mammalian JNK and p38 pathways arose from an ancestral hyperosmolarity pathway after the split from yeast and before the split from C. elegans. These coduplications of interacting proteins at the MAPK and MEK levels have since evolved toward substrate specificity, thus giving distinct pathways. Mammalian duplications since the split from C. elegans are often associated with divergent tissue distribution but do not appear to confer detectable substrate specificity. The yeast kinase cascades have undergone similar fundamental functional changes since the split from mammals, with duplications giving rise to central signaling components of the filamentous and hypoosmolarity pathways. Experimentally defined cross-talk between yeast pheromone and hyperosmolarity pathways is mirrored with corresponding cross-talk in mammalian pathways, suggesting the existence of ancient orthologous cross-talk; our analysis of gene duplications at all levels of the cascade is consistent with this model but does not always provide significant bootstrap support. Our data also provide insights at different levels of the cascade where conflicting experimental evidence exists.

Key words: Gene duplication — Signal transduction — MAP kinase — MEK — MKK — MEKK — JNK — p38

Copyright information

© Springer-Verlag New York Inc. 1999

Authors and Affiliations

  • Daniel R.  Caffrey
    • 1
  • Luke A.J.  O'Neill
    • 2
  • Denis C.  Shields
    • 1
  1. 1.Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, IrelandIE
  2. 2.Department of Biochemistry and Biotechnology Institute, Trinity College, University of Dublin, Dublin 2, IrelandIE