Extrinsic Stochastic Variations in Gene Expression

Source: Volfson et al. (2006). Origins of extrinsic variability in eukaryotic gene expression. Nature 439:861-864.

Stochastic variation in gene expression across a clonal population has been observed. These variation are classifies as either intrinsic or extrinsic variation. Intrinsic phenomona result from the inherent noise in the regulatory element that control a given gene; whereas, extrinsic variations are caused by more global or environmental stochastic processes.

To address extrinsic variation, the authors make yeast strains with 1, 2 ... 5 gal'-GFP copies. Then they use FACS machines to measure th expression of GFP in each cell. They sh

ow that, on average, GFP expression normalized by copy number is similar in all strains, denoting that the system is not saturated. Then, they hypothesize that intrinsic and extrinsic variation can be distinguished as intrinsic variation affects only one copy; whereas, extrinsic variations affect all the copies simultaneuously. In other words, if the variations are completely intrinsic then the standard deviation divided by the mean i

s proportional to the square root of copy numbers; while, if all the variation are caused by extrinsic factors this value should be independent of copy number.

The Gal system used by the authors largely falls into the second category. The authors then go on to model and validate their observations that falls outside the scope of this summary and I encourage those who are interested to read the original paper.