期刊
CELL REPORTS
卷 7, 期 6, 页码 1789-1795出版社
CELL PRESS
DOI: 10.1016/j.celrep.2014.05.018
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资金
- NSF [CCF-0905536, DBI 1062455, MCB1022327]
- NIH [GM079656, GM066099, 1R01GM088653, NIAID P30AI036211, NCI P30CA125123, NCRR S10RR024574]
- Keck Center of the Gulf Coast Consortia
- National Library of Medicine (NLM) [T15LM007093]
- IRACDA training grant [K12 GM084897]
- Direct For Biological Sciences
- Div Of Biological Infrastructure [1062455] Funding Source: National Science Foundation
Natural selection for specific functions places limits upon the amino acid substitutions a protein can accept. Mechanisms that expand the range of tolerable amino acid substitutions include chaperones that can rescue destabilized proteins and additional stability-enhancing substitutions. Here, we present an alternative mechanism that is simple and uses a frequently encountered network motif. Computational and experimental evidence shows that the self-correcting, negative-feedback gene regulation motif increases repressor expression in response to deleterious mutations and thereby precisely restores repression of a target gene. Furthermore, this ability to rescue repressor function is observable across the Eubacteria kingdom through the greater accumulation of amino acid substitutions in negative-feedback transcription factors compared to genes they control. We propose that negative feedback represents a self-contained genetic canalization mechanism that preserves phenotype while permitting access to a wider range of functional genotypes.
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