We combine molecular dynamics simulations and density functional theory to analyze the electrical structure and transmission probability in four different DNA sequences under physiological conditions. The conductance in these sequences is primarily controlled by interstrand and intrastrand coupling between low-energy guanine orbitals. Insertion of adenine-thymine base pairs between the guanine-cytosine rich domains acts as a tunneling barrier. Our theory explains recent length dependent conductance data for individual DNA molecules in water.