title: Restoration of native folding of single-stranded DNA sequences through reverse mutations: an indication of a new epigenetic mechanism.
abstract: We used in vivo (biological), in silico (computational structure prediction), and in vitro (model sequence folding) analyses of single-stranded DNA sequences to show that nucleic acid folding conservation is the selective principle behind a high-frequency single-nucleotide reversion observed in a three-nucleotide mutated motif of the Maize streak virus replication associated protein (Rep) gene. In silico and in vitro studies showed that the three-nucleotide mutation adversely affected Rep nucleic acid folding, and that the single-nucleotide reversion [C(601)A] restored wild-type-like folding. In vivo support came from infecting maize with mutant viruses: those with Rep genes containing nucleotide changes predicted to restore a wild-type-like fold [A(601)/G(601)] preferentially accumulated over those predicted to fold differently [C(601)/T(601)], which frequently reverted to A(601) and displaced the original population. We propose that the selection of native nucleic acid folding is an epigenetic effect, which might have broad implications in the evolution of plants and their viruses.
authors.affiliation: Department of Molecular and Cell Biology, University of Cape Town, Cape Town 7700, South Africa.
authors.forename: Dionne N
authors.initials: DN
authors.lastname: Shepherd
authors.forename: Darren P
authors.initials: DP
authors.lastname: Martin
authors.forename: Arvind
authors.initials: A
authors.lastname: Varsani
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Thomson
authors.forename: Edward P
authors.initials: EP
authors.lastname: Rybicki
authors.forename: Horst H
authors.initials: HH
authors.lastname: Klump
mesh_terms: D004279:DNA, Viral / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D009690:Nucleic Acid Conformation; D010942:Plant Viruses / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D003313:Zea mays / Q000821:virology*
chemical_list: D004279:DNA, Viral