Summing up the noise in gene networks

Abstract

Random fluctuations in genetic networks are inevitable as chemical reactions are probabilistic and many genes, RNAs and proteins are present in low numbers per cell. Such 'noise' affects all life processes and has recently been measured using green fluorescent protein (GFP). Two studies show that negative feedback suppresses noise, and three others identify the sources of noise in gene expression. Here I critically analyse these studies and present a simple equation that unifies and extends both the mathematical and biological perspectives.

Discreteness-induced concentration inversion in mesoscopic chemical systems

“…Intrinsic noise is taken into account by chemical master equations (CMEs), which are exact mesoscopic descriptions of well-stirred and thermally equilibrated gas-phase chemical systems 11 and chemical reactions occurring in well-stirred dilute solutions 12 . Unfortunately, CMEs are generally analytically intractable, and many studies have therefore resorted to the linear-noise approximation (LNA) of the CME (see, for example, refs [13][14][15][16][17][18][19].…”

The primary cilium as a gravitational force transducer and a regulator of transcriptional noise

“…The sources of noise that are associated with gene expression include: the small number of molecules that are involved in a particular biochemical reaction in the cellular space, the stochastic nature of the molecular interactions that underlie the chemical reaction, and the built-in efficiency of the transcriptional and translational processes. Most studies of the noise that is associated with gene expression have focused on transcription, and have distinguished between noise that is derived from the interaction between polymerases and DNA (intrinsic noise) and noise produced by other influences such as random fluctuations in nutrients, cell division, or regulatory inputs to the transcriptional machinery (extrinsic noise) (Elowitz et al, 2002;Paulsson, 2004). In mammalian cells, the major source of transcriptional noise is due to random fluctuations between bursts of active transcription and transcriptional inactivity (Raj et al, 2006).…”

Distinct noise-controlling roles of multiple negative feedback mechanisms in a prokaryotic operon system

“…fluorescent reporters and single-cell imaging techniques) in recently years have allowed stochastic gene expression to be quantified in vivo [1,[5][6][7]. These elegant experiments, along with theoretical studies [8],…”

“…Intrinsic noise originates from the randomness in the biochemical processes that take place in gene expression whereas extrinsic noise comes from fluctuations in other factors that influence gene expression. Effort has since been carried out by different groups aiming to separate one type of noise from another experimentally [5,6] and theoretically [8,9].…”