Chargaff's second parity rule and the kinetics of DNA replication

TL;DR

This study models DNA replication kinetics to explain Chargaff's second parity rule, showing that base-pair complementarity and low error rates naturally lead to nucleotide symmetry in DNA sequences.

Contribution

It provides a mechanistic explanation for Chargaff's second parity rule based on biochemical kinetics and replication fidelity, supported by numerical simulations.

Findings

Nucleotide fractions converge to parity rule through simulations.

Base-pair complementarity dominates replication kinetics.

Low error rates in DNA polymerases support symmetry.

Abstract

This paper presents the study of a DNA replication model grounded in the biochemical kinetics of DNA polymerases, which copy each DNA strand into a complementary strand, except for rare point-like mutations caused by nucleotide substitution errors. Numerical simulations of many successive replications, starting from an arbitrary initial DNA sequence, show that the fractions of mono- and oligonucleotides converge toward compliance with Chargaff's second parity rule. The theoretical framework developed for this multireplication process demonstrates that the near-equalities of complementary nucleotide fractions arise from two key features: (1) the dominant role of base-pair complementarity in replication kinetics and (2) the low intrinsic error rate of DNA polymerases. Together, these two features yield a robust mechanistic basis for Chargaff's second parity rule. These considerations explain the existence of deviations with respect to the predictions of models assuming no-strand-bias conditions.