Gene Expression Noise

One of the most striking aspects of biology is in the diversity of cellular life. Although much of this variability has been attributed to genetic and environmental factors, recent studies have shown4 that genetically identical organisms in the same environment exhibit heterogeneity in gene expression. This phenomenon, gene expression noise, has been observed and measured across species as divergent as prokaryotes and mammalian cells.1-4

We have been keenly interested in understanding more about the origin of this heterogeneity as well as wondering what potential functional consequences it may have. We have begun addressing these questions with a suite of experiments described in the following chapters.

In Chapter 1, we examine the effects selection may have on gene expression noise in silico. We find that under fairly general conditions, directional selection for the value of a quantitative phenotypic trait can yield an increase in the noise in that trait.

In Chapter 2, we begin to look experimentally at the effects cis-regulatory mutations have on gene expression noise. Through the creation of promoter mutant libraries, we look for mutations that change noise; furthermore, by also looking at how these same mutations affect mean levels of gene expression noise, we test the independence of these two parameters. By measuring mean and noise levels of gene expression in three mutant yeast promoter libraries, we see that the two parameters are independent in some cases. More importantly, we see a wide variety of mean and noise values, suggesting that cis-regulatory mutations can control gene expression noise independently of mean.

Upon finding out that specific promoter mutations can impact gene expression noise, we were in...

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...will help uncover mechanistic insights into the observed fast bursts.

To summarize, we have looked at different potential mechanisms for generating gene expression noise, namely selection, cis-regulatory mutations, and the localization of trans-acting factors. All appear as if they could contribute to gene expression noise; most notably, the bursting of transcription factors in and out of the nucleus, in addition to leading to increased amounts of gene expression noise, also yields proportional control of a suite of genes. These results also provide a mechanism for proportional control, a phenomenon which may be important in several contexts and may even provide a rationale for some of the gene expression noise that we observe. We anticipate that further investigation of the functional consequences of noise will continue to provide insights into cellular behavior.