KEY PUBLICATIONS

Alternative modes of client binding enable functional plasticity of Hsp70
Alireza Mashaghi et al. | Nature 539, 448-451 (2016) | pdf & DOI: 10.1038/nature20137
Stochasticity of metabolism and growth at the single-cell level
Daniel J. Kiviet et al. | Nature 514, 376-379 (2014) | pdf & DOI: 10.1038/nature13582
Reshaping of the conformational search of a protein by the chaperone trigger factor
Alireza Mashaghi et al. | Nature 500, 98-101 (2013) | pdf & DOI: 10.1038/nature12293
Tradeoffs and optimality in the evolution of gene regulation
Frank J. Poelwijk et al. | Cell 146, 462-470 (2011) | pdf & DOI:10.1016/j.cell.2011.06.035
Direct Observation of Chaperone-Induced Changes in a Protein Folding Pathway
Philipp Bechtluft, Ruud van Leeuwen et al. | Science 318:1458-1461 (2007) | pdf & DOI:10.1126/science.1144972
Empirical fitness landscapes reveal accessible evolutionary paths
Frank Poelwijk, Daan Kiviet et al. | Nature 445:383-386 (2007) | pdf & DOI:10.1038/nature05451
The bacteriophage phi29 portal motor can package DNA against a large internal force
Douglas E. Smith, Sander J. Tans et al. | Nature 413:748-52 (2001) | pdf & DOI:10.1038/35099581
Molecular transistors: Potential modulations along carbon nanotubes
Sander J. Tans, Cees Dekker. | Nature 404:834-35 (2000) | pdf & DOI:10.1038/35009026
Imaging electron wave functions of quantized energy levels in carbon nanotubes
Liesbeth C. Venema et al. | Science 283:52-55 (1999) | pdf & DOI:10.1126/science.283.5398.52
Electron-electron correlations in carbon nanotubes
Sander J. Tans et al. | Nature 394:761-64 (1998) | pdf & DOI:10.1038/29494
Room-temperature transistor based on a single carbon nanotube
Sander J. Tans, Alwin R. M. Verschueren & Cees Dekker | Nature 393:49-52 (1998) | pdf & DOI:10.1038/29954
Individual single-wall carbon nanotubes as quantum wires
Sander J. Tans et al. | Nature 386:474-77 (1997) | pdf & DOI:10.1038/386474a0
Fullerene 'crop circles'
Jie Liu et al. | Nature 385, 780-781 (1997) | pdf & DOI:10.1038/385780b0

Sign epistasis caused by hierarchy within signalling cascades

Nghe, P.; Kogenaru, M.; Tans, S. J.
Abstract:
Sign epistasis is a central evolutionary constraint, but its causal factors remain difficult to predict. Here we use the notion of parameterised optima to explain epistasis within a signalling cascade, and test these predictions in Escherichia coli. We show that sign epistasis arises from the benefit of tuning phenotypic parameters of cascade genes with respect to each other, rather than from their complex and incompletely known genetic bases. Specifically, sign epistasis requires only that the optimal phenotypic parameters of one gene depend on the phenotypic parameters of another, independent of other details, such as activating or repressing nature, position within the cascade, intra-genic pleiotropy or genotype. Mutational effects change sign more readily in downstream genes, indicating that optimising downstream genes is more constrained. The findings show that sign epistasis results from the inherent upstream-downstream hierarchy between signalling cascade genes, and can be addressed without exhaustive genotypic mapping.
Year:
2018
Type of Publication:
Article
Journal:
Nat Commun
Volume:
9
Number:
1
Pages:
1451
Month:
April
Note:
[PubMed Central:\href{https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899173}{PMC5899173}] [DOI:\href{https://dx.doi.org/10.1038/s41467-018-03644-8}{10.1038/s41467-018-03644-8}] [PubMed:\href{https://www.ncbi.nlm.nih.gov/pubmed/29654280}{29654280}]
Hits: 282