1. Evolutionary Biology
Download icon

Intermolecular epistasis shaped the function and evolution of an ancient transcription factor and its DNA binding sites

  1. Dave W Anderson
  2. Alesia N McKeown
  3. Joseph W Thornton  Is a corresponding author
  1. University of Oregon, United States
  2. University of Chicago, United States
Research Article
  • Cited 34
  • Views 3,253
  • Annotations
Cite this article as: eLife 2015;4:e07864 doi: 10.7554/eLife.07864

Abstract

Complexes of specifically interacting molecules, such as transcription factor proteins (TFs) and the DNA response elements (REs) they recognize, control most biological processes, but little is known concerning the functional and evolutionary effects of epistatic interactions across molecular interfaces. We experimentally characterized all combinations of genotypes in the joint protein-DNA sequence space defined by an historical transition in TF-RE specificity that occurred some 500 million years ago in the DNA-binding domain (DBD) of an ancient steroid hormone receptor. We found that rampant epistasis within and between the two molecules was essential to specific TF-RE recognition and to the evolution of a novel TF-RE complex with unique derived specificity. Permissive and restrictive epistatic mutations across the TF-RE interface opened and closed potential evolutionary paths accessible by the other, making the evolution of each molecule contingent on its partner's history and allowing a molecular complex with novel specificity to evolve.

Article and author information

Author details

  1. Dave W Anderson

    Institute of Ecology and Evolution, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Alesia N McKeown

    Institute of Ecology and Evolution, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Joseph W Thornton

    Department of Ecology and Evolution, University of Chicago, Chicago, United States
    For correspondence
    joet1@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Detlef Weigel, Max Planck Institute for Developmental Biology, Germany

Publication history

  1. Received: April 2, 2015
  2. Accepted: June 13, 2015
  3. Accepted Manuscript published: June 15, 2015 (version 1)
  4. Version of Record published: July 14, 2015 (version 2)

Copyright

© 2015, Anderson et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,253
    Page views
  • 759
    Downloads
  • 34
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Computational and Systems Biology
    2. Evolutionary Biology
    Rahil Taujale et al.
    Research Article
    1. Evolutionary Biology
    Yujun Cui et al.
    Research Article Updated