New gene evolution in the bonus-TIF1-γ/TRIM33 family impacted the architecture of the vertebrate dorsal-ventral patterning network

Mol Biol Evol. 2014 Sep;31(9):2309-21. doi: 10.1093/molbev/msu175. Epub 2014 May 31.


Uncovering how a new gene acquires its function and understanding how the function of a new gene influences existing genetic networks are important topics in evolutionary biology. Here, we demonstrate nonconservation for the embryonic functions of Drosophila Bonus and its newest vertebrate relative TIF1-γ/TRIM33. We showed previously that TIF1-γ/TRIM33 functions as an ubiquitin ligase for the Smad4 signal transducer and antagonizes the Bone Morphogenetic Protein (BMP) signaling network underlying vertebrate dorsal-ventral axis formation. Here, we show that Bonus functions as an agonist of the Decapentaplegic (Dpp) signaling network underlying dorsal-ventral axis formation in flies. The absence of conservation for the roles of Bonus and TIF1-γ/TRIM33 reveals a shift in the dorsal-ventral patterning networks of flies and mice, systems that were previously considered wholly conserved. The shift occurred when the new gene TIF1-γ/TRIM33 replaced the function of the ubiquitin ligase Nedd4L in the lineage leading to vertebrates. Evidence of this replacement is our demonstration that Nedd4 performs the function of TIF1-γ/TRIM33 in flies during dorsal-ventral axis formation. The replacement allowed vertebrate Nedd4L to acquire novel functions as a ubiquitin ligase of vertebrate-specific Smad proteins. Overall our data reveal that the architecture of the Dpp/BMP dorsal-ventral patterning network continued to evolve in the vertebrate lineage, after separation from flies, via the incorporation of new genes.

Keywords: Bonus/TIF1/TRIM; Dorsal/NF-κB; Dpp/BMP/TGF-β; Drosophila; dorsal–ventral axis; embryonic development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bayes Theorem
  • Body Patterning
  • Drosophila Proteins / agonists
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism
  • Evolution, Molecular*
  • Humans
  • Mice
  • Nedd4 Ubiquitin Protein Ligases
  • Phylogeny
  • Signal Transduction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • Vertebrates / embryology*
  • Vertebrates / genetics*


  • Bon protein, Drosophila
  • Drosophila Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Transcription Factors
  • dpp protein, Drosophila
  • Nedd4 Ubiquitin Protein Ligases
  • Nedd4 protein, human
  • Nedd4L protein, human
  • Nedd4l protein, mouse
  • Ubiquitin-Protein Ligases