A primary cause of the variability (noise) in gene expression occurring between cells in isogenic populations ^[1]. A major source of transcriptional noise is likely to be transcriptional bursting^[2][3][4]. Bursting transcription, as opposed to simple probabilistic models of transcription, reflects multiple states of gene activity, with fluctuations between states separated by irregular intervals, generating uneven protein expression between cells ^[5]. Noise in gene expression can have tremendous consequences on cell behaviour, and must be mitigated or integrated. In certain contexts, such as the survival of microbes in rapidly changing stressful environments, or several types of scattered differentiation, the variability may be essential. Variability also impacts upon the effectiveness of clinical treatment, with resistance of bacteria to antibiotics demonstrably caused by non-genetic differences^[6]. Variability in gene expression may also contribute to resistance of sub-populations of cancer cells to chemotherapy^[7].

[edit] Notes

1. ^ Raj, A; Van Oudenaarden, A (2008). "Nature, nurture, or chance: stochastic gene expression and its consequences". Cell 135 (2): 216–26. doi:10.1016/j.cell.2008.09.050. PMID 18957198. 
2. ^ Golding, I; Paulsson, J; Zawilski, SM; Cox, EC (2005). "Real-time kinetics of gene activity in individual bacteria". Cell 123 (6): 1025–36. doi:10.1016/j.cell.2005.09.031. PMID 16360033. 
3. ^ Chubb, JR; Trcek, T; Shenoy, SM; Singer, RH (2006). "Transcriptional pulsing of a developmental gene". Current biology : CB 16 (10): 1018–25. doi:10.1016/j.cub.2006.03.092. PMID 16713960. 
4. ^ Raj, A; Peskin, CS; Tranchina, D; Vargas, DY; Tyagi, S (2006). "Stochastic mRNA synthesis in mammalian cells". PLoS biology 4 (10): e309. doi:10.1371/journal.pbio.0040309. PMID 17048983. 
5. ^ Raj, A; Van Oudenaarden, A (2008). "Nature, nurture, or chance: stochastic gene expression and its consequences". Cell 135 (2): 216–26. doi:10.1016/j.cell.2008.09.050. PMID 18957198. 
6. ^ Brock, A.; Chang, H.; Huang, S. (2009). "Non-genetic heterogeneity — a mutation-independent driving force for the somatic evolution of tumours". Nature Reviews Genetics 10: 336. doi:10.1038/nrg2556.  edit
7. ^ Brock A, Chang H, Huang S. (2009). "Non-genetic heterogeneity--a mutation-independent driving force for the somatic evolution of tumours.". Nat Rev Genet 10 (5): 336–42. doi:10.1038/nrg2556. PMID 6348026.  edit