Ancient mechanisms for the evolution of the bicoid homeodomain's function in fly development

Qinwen Liu, Pinar Onal, Rhea R. Datta, Julia M. Rogers, Urs Schmidt-Ott, Martha L. Bulyk, Stephen Small, Joseph W. Thornton

Research output: Contribution to journalArticle

Abstract

The ancient mechanisms that caused developmental gene regulatory networks to diversify among distantly related taxa are not well understood. Here we use ancestral protein reconstruction, biochemical experiments, and developmental assays of transgenic animals carrying reconstructed ancestral genes to investigate how the transcription factor Bicoid (Bcd) evolved its central role in anterior-posterior patterning in flies. We show that most of Bcd's derived functions are attributable to evolutionary changes within its homeodomain (HD) during a phylogenetic interval >140 million years ago. A single substitution from this period (Q50K) accounts almost entirely for the evolution of Bcd's derived DNA specificity in vitro. In transgenic embryos expressing the reconstructed ancestral HD, however, Q50K confers activation of only a few of Bcd's transcriptional targets and yields a very partial rescue of anterior development. Adding a second historical substitution (M54R) confers regulation of additional Bcd targets and further rescues anterior development. These results indicate that two epistatically interacting mutations played a major role in the evolution of Bcd's controlling regulatory role in early development. They also show how ancestral sequence reconstruction can be combined with in vivo characterization of transgenic animals to illuminate the historical mechanisms of developmental evolution.

Original languageEnglish (US)
JournaleLife
Volume7
DOIs
StatePublished - Oct 9 2018

Fingerprint

Genetically Modified Animals
Diptera
Animals
Substitution reactions
Genes
Developmental Genes
Gene Regulatory Networks
Assays
Transcription Factors
Embryonic Structures
Chemical activation
Mutation
DNA
Proteins
Experiments
In Vitro Techniques

Keywords

  • ancestral reconstruction
  • D. melanogaster
  • evolution of development
  • genetics
  • genomics
  • homeodomain proteins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Liu, Q., Onal, P., Datta, R. R., Rogers, J. M., Schmidt-Ott, U., Bulyk, M. L., ... Thornton, J. W. (2018). Ancient mechanisms for the evolution of the bicoid homeodomain's function in fly development. eLife, 7. https://doi.org/10.7554/eLife.34594

Ancient mechanisms for the evolution of the bicoid homeodomain's function in fly development. / Liu, Qinwen; Onal, Pinar; Datta, Rhea R.; Rogers, Julia M.; Schmidt-Ott, Urs; Bulyk, Martha L.; Small, Stephen; Thornton, Joseph W.

In: eLife, Vol. 7, 09.10.2018.

Research output: Contribution to journalArticle

Liu, Q, Onal, P, Datta, RR, Rogers, JM, Schmidt-Ott, U, Bulyk, ML, Small, S & Thornton, JW 2018, 'Ancient mechanisms for the evolution of the bicoid homeodomain's function in fly development', eLife, vol. 7. https://doi.org/10.7554/eLife.34594
Liu, Qinwen ; Onal, Pinar ; Datta, Rhea R. ; Rogers, Julia M. ; Schmidt-Ott, Urs ; Bulyk, Martha L. ; Small, Stephen ; Thornton, Joseph W. / Ancient mechanisms for the evolution of the bicoid homeodomain's function in fly development. In: eLife. 2018 ; Vol. 7.
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