DNA resembles a twisted ladder. And the rungs of the DNA ladder are complementary pairs of nitrogenous bases. According to base pairing rules, adenine, a purine, pairs with thymine, a pyrimidine, with two hydrogen bonds. And guanine, a purine, appears with cytosine, a pyrimidine, with three hydrogen bonds. But why do purines always pair with pyrimidines?

Due to steric constraints, that is, spatial restrictions imposed by the sugar phosphate backbone of the DNA, only a 10.85 angstrom space is available for the base pairs in a DNA double helix.

Purines have a double ring structure. Therefore, two purines together will be too big to fit in this space. On the other hand, if we put two pyrimidines together, which contain only a single ring, the distance between them will be too large to form hydrogen bonds, which are approximately two angstroms long.

However, if we pair a purine and a pyrimidine together, they fit perfectly inside the DNA helix and are close enough to form hydrogen bonds. Hydrogen bonds can form when a hydrogen atom is approximately two angstroms away from an electronegative atom, such as oxygen or nitrogen.

Adenine has one hydrogen atom close to an oxygen and thymine. And thymine has one hydrogen close to a nitrogen and adenine. This leads to the formation of two hydrogen bonds.

Adenine cannot form hydrogen bonds with cytosine, because cytosine has a hydrogen atom where the oxygen and thymine would be. And the hydrogen atom that is present in thymine is absent in cytosine.

A similar phenomenon occurs in the guanine cytosine base pair where an oxygen in guanine, and an oxygen and a nitrogen in cytosine are each positioned across from a hydrogen, leading to the formation of three hydrogen bonds, which does not happen in guanine thymine base pairing.

The high specificity of base pairing, along with the help of DNA replication enzymes, is why adenine always pairs with thymine and guanine always pairs with cytosine.