Robustness–epistasis link shapes the fitness landscape of a randomly drifting protein

By S. Bershtein, M. Segal, R. Bekerman, Nobuhiko Tokuriki, Dan S. Tawfik. 2006

419 citations recorded by the source corpus.

Subfields: Genetics, Public Health, Environmental and Occupational Health, Sociology and Political Science

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Citations in the corpus

A biophysical protein folding model accounts for most mutational fitness effects in viruses (2011, methodology): “(25) was reused to estimate the DFE for this enzyme (27).”
A systems analysis of mutational effects in HIV-1 protease and reverse transcriptase (2011, neutral): “Because protein structure and epistasis are interrelate”
High Resolution Mapping of Protein Sequence–Function Relationships (2010, background): “How multiple mutations interact is an important question in protein science and evolutio”
Machine learning-assisted directed protein evolution with combinatorial libraries (2019, background): “…of beneficial mutations, circumventing the need for indirect paths (16) or alterations of the nature of selection (31), and potentially avoiding negative epistatic effects resulting from the accumulation of large numbers of mutations (33) that require reversion later in the evolution (34).”
Stability effects of mutations and protein evolvability. (2009, background): “This result is in agreement with in vitro measurements of fitness losses, and the threshold model, by which, once the margin of stability is compromised, mutations cause immediate fitness losses [2,4].”
Soluble oligomerization provides a beneficial fitness effect on destabilizing mutations (2011, background): “Unlike earlier approaches, which considered how overexpression of non-endogenous destabilized proteins from a plasmid affects fitness (5, 15, 16), we aimed to establish the link between the molecular properties of an endogenous essential protein and organismal fitness at maximally realistic conditio”
The genetic landscape of a physical interaction (2018, background): “Additional non-linearities occur in the folding of individual proteins or RNAs (‘threshold robustness’) (Bershtein et al., 2006; Olson et al., 2014; Tokuriki and Tawfik, 2009), in saturating enzyme flux (Kacser and Burns, 1973; Stiffler et al., 2015), and in regulatory dynamics (Gjuvsland et al.,…”
A Comprehensive, High-Resolution Map of a Gene’s Fitness Landscape (2014, methodology): “Previous partial characterizations of the DFE of TEM-1 (Bershtein et al. 2006; Deng et al. 2012; Jacquier et al. 2013) suffer several significant limitations.”