000			02145 am a22002413u 4500
042			_adc
100	1	0	_aKarve, Shraddha _eauthor _91241
700	1	0	_aDasmeh, Pouria _eauthor _91242
700	1	0	_aZheng, Jia _eauthor _91243
700	1	0	_aWagner, Andreas _eauthor _91244
245	0	0	_aLow protein expression enhances phenotypic evolvability by intensifying selection on folding stability
260			_c2022-08.
500			_a/pmc/articles/PMC7613228/
500			_a/pubmed/35798838
520			_aProtein abundance affects the evolution of protein genotypes, but we do not know how it affects the evolution of protein phenotypes. Here we investigate the role of protein abundance on the evolvability of green fluorescent protein (GFP) towards the novel phenotype of cyan fluorescence. We evolve GFP in E.coli through multiple cycles of mutation and selection, and show that low GFP expression facilitates the evolution of cyan fluorescence. A computational model whose predictions we test experimentally helps explain why: Lowly expressed proteins are under stronger selection for proper folding, which facilitates their evolvability on short evolutionary time scales. The reason is that high fluorescence can be achieved by either few proteins that fold well, or by many proteins that fold less well. In other words, we observe a synergy between a protein's scarcity and its stability. Because many proteins meet the essential requirements for this scarcity-stability synergy, it may be a widespread mechanism by which low expression helps proteins evolve new phenotypes and functions.
540			_a
540			_ahttps://www.springernature.com/gp/open-research/policies/accepted-manuscript-termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: (https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
546			_aen
690			_aArticle
655	7		_aText _2local
786	0		_nNat Ecol Evol
856	4	1	_uhttp://dx.doi.org/10.1038/s41559-022-01797-w _zConnect to this object online.
999			_c1615 _d1615