Gene regulatory network plasticity predates a switch in function of a conserved transcription regulator

Abstract
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Abstract

The rewiring of gene regulatory networks can generate phenotypic novelty. It remains an open question, however, how the large number of connections needed to form a novel network arise over evolutionary time. Here we address this question using the network controlled by the fungal transcription regulator Ndt80. This conserved protein has undergone a dramatic switch in function—from an ancestral role regulating sporulation to a derived role regulating biofilm formation. This switch in function corresponded to a large-scale rewiring of the genes regulated by Ndt80. However, we demonstrate that the Ndt80-target gene connections were undergoing extensive rewiring prior to the switch in Ndt80’s regulatory function. We propose that extensive drift in the Ndt80 regulon allowed for the exploration of alternative network structures without a loss of ancestral function, thereby facilitating the formation of a network with a new function.

Data availability

The following previously published data sets were used

1. Chu S
2. DeRisi J
3. Eisen M
4. Mulholland J
5. Botstein D
6. Brown PO
7. Herskowitz I
(1998) The transcriptional program of sporulation in budding yeast
Also available at the NCBI Gene Expression Omnibus (accession no: GDS104).

http://cmgm.stanford.edu/pbrown/sporulation/

Article and author information

Author details

Isabel Nocedal

Department of Biology, Massachusetts Institute of Technology, Cambridge, United States

For correspondence
inocedal@gmail.com

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4706-1113
Eugenio Mancera

Departamento de Ingeniería Genética, Cinvestav Unidad Irapuato, Irapuaro, Mexico

Competing interests
The authors declare that no competing interests exist.
Alexander D Johnson

Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States

For correspondence
ajohnson@cgl.ucsf.edu

Competing interests
The authors declare that no competing interests exist.

Funding

National Institutes of Health (R01 GM037049)

Isabel Nocedal
Eugenio Mancera
Alexander D Johnson

Human Frontier Science Program

Eugenio Mancera

UC-MEXUS

Eugenio Mancera

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

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.