CORDIS
EU research results

CORDIS

English EN
Noise and robustness in the evolution of novel protein phenotypes

Noise and robustness in the evolution of novel protein phenotypes

Objective

Living cells are constantly barraged by perturbations that originate within themselves. Especially abundant – far more than DNA mutations – are two kinds of such perturbations. The first is gene expression noise, pervasive stochastic variation of transcript and protein levels. The second is mistranslation noise, the misincorporation of amino acids by ribosomes during protein synthesis. Organisms and protein molecules can evolve robustness – the persistence of well-adapted phenotypes – to both kinds of noise. Theory predicts that noise and robustness can affect the adaptive evolution of new proteins, but we do not know whether they help or hinder adaptive evolution. We hypothesize that noise and robustness can accelerate protein evolution both separately and jointly. To validate this hypothesis, we will evolve light-emitting fluorescent proteins towards new color phenotypes via directed laboratory evolution in E.coli. During evolution, we will manipulate expression noise by driving FP expression from noisy or quiet promoters, and we will manipulate mistranslation via host strains with low and high mistranslation rates. We will manipulate protein robustness in three biologically important ways, chaperone overexpression, gene duplication, and stabilizing selection. We will study how fast FPs evolve new colors, and analyze protein evolutionary dynamics through a combination of high-throughput sequencing, engineering of selected adaptive mutations, and data-driven modeling. Our project will show how a ubiquitous but poorly understood source of phenotypic variation affects protein innovation. It will also help engineers discover new protein functions. Moreover, our work will help establish FPs as a major platform to study protein evolutionary dynamics. By revealing noise as a new and crucial factor in protein evolution, our observations have the potential to revolutionize molecular evolution research, much like earlier studies of noise have revolutionized cell biology.
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Host institution

UNIVERSITAT ZURICH

Address

Ramistrasse 71
8006 Zurich

Switzerland

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 2 383 444

Beneficiaries (1)

Sort alphabetically

Sort by EU Contribution

Expand all

UNIVERSITAT ZURICH

Switzerland

EU Contribution

€ 2 383 444

Project information

Grant agreement ID: 739874

Status

Ongoing project

  • Start date

    1 October 2017

  • End date

    30 September 2022

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 383 444

  • EU contribution

    € 2 383 444

Hosted by:

UNIVERSITAT ZURICH

Switzerland