title: Imperfect DNA lesion repair in the semiconservative quasispecies model: derivation of the Hamming class equations and solution of the single-fitness peak landscape.
abstract: This paper develops a Hamming class formalism for the semiconservative quasispecies equations with imperfect lesion repair, first presented and analytically solved in Y. Brumer and E.I. Shakhnovich (q-bio.GN/0403018, 2004). Starting from the quasispecies dynamics over the space of genomes, we derive an equivalent dynamics over the space of ordered sequence pairs. From this set of equations, we are able to derive the infinite sequence length form of the dynamics for a class of fitness landscapes defined by a master genome. We use these equations to solve for a generalized single-fitness-peak landscape, where the master genome can sustain a maximum number of lesions and remain viable. We determine the mean equilibrium fitness and error threshold for this class of landscapes, and show that when lesion repair is imperfect, semiconservative replication displays characteristics from both conservative replication and semiconservative replication with perfect lesion repair. The work presented here provides a formulation of the model which greatly facilitates the analysis of a relatively broad class of fitness landscapes, and thus serves as a convenient springboard into biological applications of imperfect lesion repair.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. etannenb@fas.harvard.edu
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Tannenbaum
authors.forename: James L
authors.initials: JL
authors.lastname: Sherley
authors.forename: Eugene I
authors.initials: EI
authors.lastname: Shakhnovich
mesh_terms: D000818:Animals; D020137:Base Pair Mismatch / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods; D003198:Computer Simulation; D004249:DNA Damage / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D019143:Evolution, Molecular; D014644:Genetic Variation / Q000235:genetics; D005828:Genetics, Population; D006801:Humans; D008957:Models, Genetic; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*; D013489:Suppression, Genetic / Q000235:genetics*