A functional selection model explains evolutionary robustness despite plasticity in regulatory networks

Molecular Systems Biology

Naomi Habib⁴  Ilan Wapinski¹  Hanah Margalit³  Aviv Regev² 

[1] Department of Systems Biology, Harvard Medical School, Boston, MA, USA;Broad Institute, 7 Cambridge Center, Cambridge, MA, USA;Department of Microbiology and Molecular Genetics, IMRIC, Faculty of Medicine, Hebrew University, Jerusalem, Israel;School of Computer Science and Engineering, Hebrew University, Jerusalem, Israel

关键词: bioinformatics;    computational methods;    evolution;    regulation;    transcription;   

DOI  :  10.1038/msb.2012.50

来源: Wiley

【 摘 要 】

Abstract

Evolutionary rewiring of regulatory networks is an important source of diversity among species. Previous evidence suggested substantial divergence of regulatory networks across species. However, systematically assessing the extent of this plasticity and its functional implications has been challenging due to limited experimental data and the noisy nature of computational predictions. Here, we introduce a novel approach to study cis-regulatory evolution, and use it to trace the regulatory history of 88 DNA motifs of transcription factors across 23 Ascomycota fungi. While motifs are conserved, we find a pervasive gain and loss in the regulation of their target genes. Despite this turnover, the biological processes associated with a motif are generally conserved. We explain these trends using a model with a strong selection to conserve the overall function of a transcription factor, and a much weaker selection over the specific genes it targets. The model also accounts for the turnover of bound targets measured experimentally across species in yeasts and mammals. Thus, selective pressures on regulatory networks mostly tolerate local rewiring, and may allow for subtle fine-tuning of gene regulation during evolution.

Synopsis

By tracing the evolutionary history of transcriptional networks across 23 fungi, two seemingly contradictory trends are observed: rapid target turnover and conserved function. This is reconciled by a model that invokes strong selection to conserve the overall function of a motif, but not its individual targets.

• The vast majority of cis-regulatory elements in genes’ promoters are rapidly gained and lost across species.
• Despite this rapid turnover, most transcription factors are associated with a conserved function even at great evolutionary distances.
• A functional selection turnover model reconciles these two phenomena by invoking a preference to conserve the overall function of the motif but not the individual target genes.
• Our model fits the variation in measured transcription factor binding profiles across species in both yeasts and mammals.

【 授权许可】

CC BY-NC-SA   
Copyright © 2012 EMBO and Macmillan Publishers Limited

Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.