Designs of conjugate reporters to measure the effects of different cellular subsystems on variation in output. (

*A*) To distinguish transcriptional from translational effects, three reporters are needed including a bicistronic mRNA with two independent ribosome binding sites. (

*B*) Simulated results for the reporters in

*A* assuming that extrinsic fluctuations affect only the rate of transcription, which fluctuates between three different levels (reactions and parameter values are given in

*SI Text*). Blue dots show

*Z* plotted against

*Z*^{′}: The average spread along the

*Z* =

*Z*^{′} diagonal equals the sum of

*V*[

*Z*] and the extrinsic variance; the average spread perpendicular to the diagonal equals the sum of the transcriptional and translational variation (

*SI Text*). Red dots show

*Z* plotted against

*Z*^{′′}: the average spread along the diagonal equals the sum of

*V*[

*Z*], extrinsic, and transcriptional variation; the average spread perpendicular to the diagonal equals translational variation. For the parameters chosen (

*SI Text*), the translational noise (coefficient of variation) is 0.12; the transcriptional noise is 0.39; and the extrinsic noise is 0.41. These numbers agree with Eqs.

**9** through

**11** to two decimal places. (

*C*) Four reporters are needed to distinguish transductional variation from variation generated by gene expression. Here, a signaling network activates a transcription factor,

*T*, in response to extracellular inputs. To measure variation in the output

*Z* arising from gene expression, we require two conjugate reporters,

*Z* and

*Z*^{′}, whose expression is controlled by this transcription factor. To find a bound on transductional variation, we use two further conjugate and constitutively expressed reporters,

*Z*_{c} and

.

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