Manfred Eigen publishes his error threshold theorem in 1971, showing that a genome holds together only below a precise error rate.
The Visitor watches a cell copy its 6.4 billion base pairs (two sets of 3.2 billion) and follows the three layers that correct the copy.
Three Layers, One Billion
- The polymerase makes about 1 error in 100,000 bases copied. At that rate, a diploid human cell copying 6.4 billion bases would carry about 64,000 errors per division.
- Three correction layers act one after another on each copied base (Alberts et al. 2002, Table 5-1):
- Base selection: the polymerase's active-site geometry gives about 105 accuracy (1 error in 100,000 bases).
- Proofreading: the 3' to 5' exonuclease improves accuracy about 100-fold, from 10-5 to 10-7.
- Mismatch repair: the strand-directed system improves accuracy about 100-fold, from 10-7 to 10-9. In E. coli, MutS finds the distortion, MutL recruits MutH, and the new strand is cut and rewritten.
- The layers multiply: 105 x 102 x 102 = 109. The final rate is about 1 error per billion bases (10-9), a gain of about 104 beyond base selection.
- After correction, the same cell finishes with about 6 changes per division (about 3 per 3.2 billion base set).
- Base excision repair and nucleotide excision repair add genome maintenance between replications.
Letters stream through base selection, proofreading, and mismatch repair. Red letters turn clean at the gate that catches them.
How many correction layers act during replication, and what final error rate do they reach together?
Three layers (base selection, proofreading, mismatch repair), reaching about 1 error per billion bases (10-9). A cell that would carry about 64,000 errors per division from base selection alone finishes with about 6.
Three layers (base selection, proofreading, mismatch repair) bring copying accuracy to about 1 error per billion bases.
The Visitor lights node 09 and the map connects it back to the DNA code at node 01.
See the map