Mismatch Repair Error Implies Chargaff's Second Parity Rule

TL;DR

This paper presents a Markov chain model demonstrating that mismatch repair errors in DNA lead to Chargaff's second parity rule, linking molecular mechanisms to observed base composition symmetry.

Contribution

The paper introduces a novel Markov chain model connecting mismatch repair errors to Chargaff's second parity rule, providing a testable hypothesis for molecular basis of the rule.

Findings

Steady state probabilities equal for complementary bases due to mismatch repair.

Chargaff's rule emerges from the Law of Large Numbers applied to the model.

Model suggests experimental verification of mismatch repair's role.

Abstract

Chargaff's second parity rule holds empirically for most types of DNA that along single strands of DNA the base contents are equal for complimentary bases, A = T, G = C. A Markov chain model is constructed to track the evolution of any single base position along single strands of genomes whose organisms are equipped with replication mismatch repair. Under the key assumptions that mismatch error rates primarily depend the number of hydrogen bonds of nucleotides and that the mismatch repairing process itself makes strand recognition error, the model shows that the steady state probabilities for any base position to take on one of the 4 nucleotide bases are equal for complimentary bases. As a result, Chargaff's second parity rule is the manifestation of the Law of Large Number acting on the steady state probabilities. More importantly, because the model pinpoints mismatch repair as a basis of the rule, it is suitable for experimental verification.