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June 17, 2015

Inaccuracy as a survival strategy

Do not put all your eggs in one basket. This can be a successful strategy for populations of cells to survive environmental changes. The research group of Prof. Erik van Nimwegen at the Biozentrum of the University of Basel has shown that variation in gene expression can be a beneficial trait that improves the fitness of an individual. In their recent publication in “eLife”, the scientists provide new insights into the interplay between noise and the evolution of gene regulation.

Two populations of E. coli cells expressing green fluorescent protein GFP from two different promoters: A high noise promoter in the cells on the left, and a low noise promoter in the cells on the right.

Whether in the deep sea, in the soil, or in the gut, environmental conditions can often change rapidly and drastically. One possible strategy to cope with such challenges is to diversify the traits and behavior of individual cells, even when these cells are genetically identical. This strategy increases the chances that at least some individuals can survive the environmental changes.

Unexpected: noisy expression of natural bacterial genes

Variation in phenotypic traits between genetically identical cells can arise because gene expression is subject to noise. So far, most researchers assumed that natural selection tries to minimize the amount of variation, i.e. noise in gene expression that regulatory DNA sequences, called promoters, cause. Here, the research of Prof. Erik van Nimwegen from the Biozentrum of the University of Basel comes into play: He and his team measured how natural selection has affected noise levels. “Very surprisingly, and absolutely contrary to our expectations, we found that in the bacterium Escherichia coli, artificially synthesized promoters have clearly lower levels of noise than many of the natural promoters,” says van Nimwegen. “We also found that the promoters of natural genes that express at different levels in different environments are typically much more noisy. We concluded that natural selection must have caused the promoters of these genes to evolve high noise levels.”

Gene expression noise can be beneficial

To better understand these observations the scientists developed a theoretical model. They showed that it can be beneficial if regulatory factors transmit their own noise to their target genes. In short: the more noisy the factor, the more diverse the expression of their respective target genes. This increase in noise levels can improve the chances of survival of offspring if the environment changes. “Our modeling shows that the transmission of noise can be beneficial in a wide range of conditions”, emphasizes van Nimwegen. “It would thus be fair to consider it as a rudimentary form of regulation.”

Insights into evolution of gene regulation

Furthermore, the study provides explanations of how gene expression can become controlled in new ways and gives insight into how new gene regulation can evolve from scratch, i.e. using noisy strategies as an intermediate in going from 'no regulation' to 'accurate regulation'. “There is thus a deep connection between the evolution of gene regulation and noise in gene expression,” concludes van Nimwegen. “In general, our model shows that, unless control of gene expression is very precise, increasing noise in gene expression is beneficial.” In conclusion, maintaining diversity often pays off: not only in terms of genetic diversity but also in terms of diversity in gene expression.

Original article:
Luise Wolf, Olin K. Silander, Erik van Nimwegen. Expression noise facilitates the evolution of gene regulation. eLife; published online 17 June 2015

Contact: Communications, Katrin Bühler