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

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.