The observation that the bases are present in different amounts in the DNAs of different species led to the concept that the
By the 1950s, the concept of genetic information was common: the twin problems it posed were working out the structure of the nucleic acid, and explaining how a sequence of bases in DNA could represent the sequence of amino acids in a protein.
Three notions converged in the construction of the double helix model for DNA by Watson and Crick in 1953:
Watson and Crick proposed that the two polynucleotide chains in the double helix associate by
hydrogen bonding between the nitrogenous bases. G can hydrogen bond specifically only with C, while A can bond specifically only with T. These reactions are described as
base pairing, and the paired bases (G with C, or A with T) are said to be
complementary.
The model proposed that the two polynucleotide chains to run in opposite directions (
antiparallel), as illustrated in Figure 1.8. Looking along the helix, one strand runs in the 5
?3
direction, while its partner runs 3
?5
(
Watson and Crick, 1953;
Wilkins, Stokes, and Wilson, 1953;
Watson and Crick, 1953).
The sugar-phosphate backbone is on the outside and carries negative charges on the phosphate groups. When DNA is in solution in vitro, the charges are neutralized by the binding of metal ions, typically by Na+. In the cell, positively charged proteins provide some of the neutralizing force. These proteins play an important role in determining the organization of DNA in the cell.
The bases lie on the inside. They are flat structures, lying in pairs perpendicular to the axis of the helix. Consider the double helix in terms of a spiral staircase: the base pairs form the treads, as illustrated schematically in Figure 1.9. Proceeding along the helix, bases are stacked above one another, in a sense like a pile of plates.
Each base pair is rotated ~36
° around the axis of the helix relative to the next base pair. So ~10 base pairs make a complete turn of 360
°. The twisting of the two strands around one another forms a double helix with a
minor groove (~12
Å across) and a
major groove (~22
Å across), as can be seen from the scale model of Figure 1.10. The double helix is
right-handed; the turns run clockwise looking along the helical axis. These features represent the accepted model for what is known as the
B-form of DNA.
It is important to realize that the B-form represents an average, not a precisely specified structure. DNA structure can change locally. If it has more base pairs per turn it is said to be overwound; if it has fewer base pairs per turn it is underwound. Local winding can be affected by the overall conformation of the DNA double helix in space or by the binding of proteins to specific sites.