Ribosome Traffic & Translation

About Translation Kinetics

This toy simulates the Totally Asymmetric Simple Exclusion Process (TASEP), a stochastic model of ribosome movement along mRNA during translation. Ribosomes act as particles that hop along a one-dimensional lattice (the mRNA) with exclusion interactions—no two ribosomes can occupy the same codon.

The TASEP Model

• Initiation (α): Ribosomes bind to the start codon with rate α (if space available)
• Elongation (β): Ribosomes move 5'→3' by one codon per time step with rate β(i), where i is the codon position
• Termination (γ): Ribosomes dissociate at the stop codon, releasing the completed protein
• Exclusion: Ribosomes occupy ~10 codons (ribosome footprint) and cannot overlap

Ribosome Traffic Jams

When a ribosome encounters a slow codon (rare codon with low tRNA abundance), it slows down. Ribosomes behind it queue up, forming a traffic jam. This phenomenon has important biological consequences:

• Reduced protein output: Traffic jams decrease the overall translation rate
• Polysome formation: Multiple ribosomes on the same mRNA create polysomes
• Co-translational folding: Slow codons can provide time for proper protein folding
• Ribosome collisions: Severe bottlenecks can cause ribosome collisions and stalling

Phase Transitions

The TASEP model exhibits three phases depending on the relative values of α (initiation), β (elongation), and γ (termination):

• Low-density phase (α < β, γ): Initiation-limited; few ribosomes on mRNA
• High-density phase (α > β, γ): Elongation-limited; mRNA saturated with ribosomes
• Maximal current phase (α ≈ β ≈ γ): Balanced rates; maximum protein production

Codon Usage and Translation Speed

Not all codons are translated at the same rate. Codon-specific elongation rates β(i) depend on:

• tRNA abundance: Rare codons have fewer cognate tRNAs, causing pauses
• Wobble base pairing: Non-Watson-Crick pairing is slower
• Codon context: Neighboring codons affect translation speed
• mRNA secondary structure: Stem-loops can stall ribosomes

Biological Implications

Understanding translation kinetics is crucial for:

• Synthetic biology: Optimizing genes for heterologous expression
• Drug design: Antibiotics like chloramphenicol target ribosome elongation
• Evolution: Selection pressure on synonymous codon usage
• Protein engineering: Co-translational folding and aggregation control

Experimental Validation

Modern ribosome profiling (Ribo-seq) experiments directly measure ribosome density along mRNAs genome-wide. These experiments have confirmed:

• Ribosomes pause at rare codons
• Polysome gradients correlate with translation efficiency
• Codon optimality affects both speed and accuracy
• Start codon region often shows ribosome queuing

Historical Context

The TASEP model was originally developed in statistical physics to study driven diffusive systems and traffic flow. Its application to translation kinetics began in the 1960s, but gained traction in the 2000s with ribosome profiling data. The model has been extended to include ribosome recycling, mRNA circularization, and interactions with chaperones and the nascent polypeptide exit tunnel.