The role of protein interactions in mediating essentiality and synthetic lethality

Talavera, D., Robertson, D. L. and Lovell, S. C. (2013) The role of protein interactions in mediating essentiality and synthetic lethality. PLoS ONE, 8(4), e62866. (doi:10.1371/journal.pone.0062866) (PMID:23638160) (PMCID:PMC3639263)

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Abstract

Genes are characterized as essential if their knockout is associated with a lethal phenotype, and these "essential genes" play a central role in biological function. In addition, some genes are only essential when deleted in pairs, a phenomenon known as synthetic lethality. Here we consider genes displaying synthetic lethality as "essential pairs" of genes, and analyze the properties of yeast essential genes and synthetic lethal pairs together. As gene duplication initially produces an identical pair or sets of genes, it is often invoked as an explanation for synthetic lethality. However, we find that duplication explains only a minority of cases of synthetic lethality. Similarly, disruption of metabolic pathways leads to relatively few examples of synthetic lethality. By contrast, the vast majority of synthetic lethal gene pairs code for proteins with related functions that share interaction partners. We also find that essential genes and synthetic lethal pairs cluster in the protein-protein interaction network. These results suggest that synthetic lethality is strongly dependent on the formation of protein-protein interactions. Compensation by duplicates does not usually occur mainly because the genes involved are recent duplicates, but is more commonly due to functional similarity that permits preservation of essential protein complexes. This unified view, combining genes that are individually essential with those that form essential pairs, suggests that essentiality is a feature of physical interactions between proteins protein-protein interactions, rather than being inherent in gene and protein products themselves.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robertson, Professor David
Authors: Talavera, D., Robertson, D. L., and Lovell, S. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
First Published:First published in PLoS ONE 8(4):e62866
Publisher Policy:Reproduced under a Creative Commons License

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