The DNA Conductor Hypothesis: Sequence-Dependent Electron Conduction as the Thermodynamic Basis of DNA-Centred Biological Function

Abstract

The prevailing description of deoxyribonucleic acid (DNA) treats the molecule primarily as an information-storage medium: a linear code that is replicated, transcribed and translated to build and operate a cell. This is not disputed here. Independently of this informational role, double-stranded DNA is also an established physical medium for charge transport: electrons move along its π-stacked bases by short-range superexchange and longer-range multi-step hopping, and DNA-bound redox-active proteins exchange electrons through the duplex over distances relevant to cellular biochemistry. This paper develops, as an explicit and falsifiable hypothesis rather than an established finding, the proposal that this sequence-dependent charge-transport property may constitute an additional physical layer of genome function, alongside DNA's informational, structural and regulatory roles. We hypothesise that the local charge-transport landscape of a genome - where the duplex preferentially opens, where it couples to donor or acceptor centres, and how it responds dielectrically - is set by local base sequence, so that this landscape is itself sequence-encoded and could, in principle, be partly predicted from sequence. We formalise this as four structural hypotheses (H1-H4) concerning directionality, base-stacking dependence, sequence-dependent local impedance, and dielectric response; We use a sign-consistent Marcus-type expression, written in terms of the donor–acceptor free energy ΔG°, to describe charge transfer along DNA. In the framework proposed here, the nucleotide sequence may determine not only genetic information but also the electronic landscape of the double helix. Because charge transfer can occur through the π-stacked bases, different sequences may create regions in which electron transfer is more or less favourable. We therefore ask whether sites used by cellular machinery - including replication origins, restriction–modification sites, and transcription-factor or RNA-polymerase binding regions in bacterial systems - may coincide with characteristic features of this electronic landscape. The corresponding question in eukaryotic chromatin is treated separately. No new experimental data are presented; the examples are intended to define measurements that could support or falsify the hypothesis and to identify the experiments that would most directly test it.