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Dissection of Enhancer Function Using Multiplex CRISPR-based Enhancer Interference in Cell Lines
Published on: June 2, 2018
Following gene duplication, paralog interference constrains transcriptional circuit evolution
Christopher R Baker1, Victor Hanson-Smith, Alexander D Johnson
1Department of Immunology and Microbiology, University of California, San Francisco, CA 94143, USA.
Science (New York, N.Y.)
|October 5, 2013
Summary
Gene duplication can lead to competitive interference between paralogs, especially for proteins in cooperative assemblies. Resolving this interference, as seen with the Mcm1 regulator, increases molecular complexity and stabilizes duplicated genes.
Area of Science:
- Evolutionary biology
- Molecular genetics
- Systems biology
Background:
- Gene duplication models often assume independent ancestral functions.
- Proteins in cooperative assemblies, like transcriptional regulators, may face unique evolutionary pressures post-duplication.
- The MADS-box transcriptional regulator Mcm1 is essential in fungi and controls numerous genes.
Purpose of the Study:
- To investigate paralog interference as a consequence of gene duplication in cooperative protein assemblies.
- To examine the evolutionary history of the Mcm1 gene and its paralogs.
- To understand how the resolution of paralog interference impacts gene regulatory network complexity.
Main Methods:
- Comparative analysis of Mcm1 gene sequences across fungal species.
- Modeling of protein interactions and regulatory network dynamics.
- Phylogenetic analysis to infer historical substitutions.
Main Results:
- Duplication and divergence of transcriptional regulators like Mcm1 can result in competitive interference between paralogs.
- Historical amino acid substitutions in Mcm1 have minimized paralog interference in extant species.
- Resolution of paralog interference has led to increased molecular complexity within the Mcm1-regulated gene network.
Conclusions:
- Paralog interference is a significant constraint on the evolution of duplicated genes, particularly those involved in complex assemblies.
- The resolution of paralog interference can drive the evolution of greater regulatory complexity.
- Minimizing paralog interference is crucial for the stable integration of duplicated genes into the genome.
Related Concept Videos
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The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are characterized.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are characterized.
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Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
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