Stochastic Gene Expression — Transcriptional Bursting

How single-gene noise creates cell-to-cell variability in protein levels

Two-State Promoter Model

Genes switch stochastically between an active (ON) and inactive (OFF) state. mRNA is produced only in bursts during ON periods, then degraded.

OFF ⇌ ON (rates: k_on, k_off)
ON → ON + mRNA (rate: k_m)
mRNA → ∅ (rate: γ_m)

The protein copy number follows a negative binomial distribution in steady state. The key parameter is the burst frequency b = k_on/k_off and burst size B = k_m/k_off.

P(n) ~ NegBin(b, B/(1+B))
Fano factor = 1 + B
CV² = 1/⟨n⟩ + (B/k_off)/⟨n⟩

This is the source of non-genetic variability (noise) in identical cells.

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