Everything that makes you special can be found in a few simple molecules stacked three billion times. Intrinsic to all organisms, the molecule deoxyribonucleic acid (DNA) accounts for the diversity of life, undoubtedly due to its unique structure and various chemo-physical interactions. DNA’s structure ensures the smooth integration of gene expression, transmission, and life. The field of biophysics applies physics concepts to appreciate biology beyond the macroscopic results of pea flower colors, kingdoms of life, or ecosystems.

DNA is a very long molecule where elements bond to each other in a specific pattern. Individual nucleotides considered DNA’s “building blocks” consist of a phosphate group, deoxyribose sugar, and one of four nitrogenous bases, adenine (A), cytosine (C), guanine (G), and thymine (T). Again, these elements must bond together at very specific sites (Figure 1). Think of a bike. Manufacturers weld the frame, attach handlebars and a seat in a schematic you probably recognize. Similarly, many nucleotides covalently bond on top of each other to form a single strand of double-helix DNA. 

If welding metal bonds a bicycle’s more rigid components, covalent bonds secure DNA’s primary structure. But we still cannot ‘ride’ a bicycle frame. We must add other parts like the wheels or a chain. Although these parts are by no means welded or firmly attached, they’re nevertheless integral to the holistic system. The hydrogen bonding interactions between DNA’s four bases give the molecule its secondary structure and, in this way, represent the mechanistically fluid parts of the bicycle. Yet, hydrogen bonds do not share electrons equally as with DNA’s covalently bonded primary structure. Despite their name, hydrogen bonds in the secondary structure are not true bonds and occur due to disparities in atoms’ affinity for electrons. Hydrogen bonding allows two opposite, complementary strands to line up against each other. So, if welding two pieces of metal may represent a covalent bond, tying or chaining up two objects can represent a hydrogen bond. Because each base molecule has a different molecular structure, hydrogen-bonding interactions only occur between specific bases and sites. You wouldn’t wrap a bicycle chain around the handlebars or attach a wheel to the seat. As a rule, T and A attach via two hydrogen bonds, while G and C attach with three hydrogen bonds (Figure 2). Like double tying your shoes, the extra hydrogen bond between G and C gives these two nucleotides an additional fortified level of stability important to parts of DNA that require extra strength. 

Yet, DNA does not exist as freely floating molecules, at least not in humans. Much like IKEA furniture, your DNA comes specially packaged, and it’s up to your transcription enzymes to assemble the proper gene expression proteins (Figure 3). Along with another few levels of molecular structure and steps, enzymes called polymerases will eventually read the sequence of base pairs in a double strand of DNA. These polymerases may replicate the DNA or transcribe an RNA copy to express your genes. Look in a mirror, and you’ll see your appearance as an ultimate product of gene expression. 

Delving back into the chemical microscale, most people first think of the molecules A, T, G, C, and uracil as all the bases in DNA and RNA. Although additional bases occur in other cellular processes, these five bases do most of the biology classroom gene coding. However, scientists discovered another coding nucleotide diaminopurine (DAP) in the 1970s that replaces A and bonds with T in a viral genetic code [1]. Additional nucleotides exist, but these do not occur in DNA strands intended for gene expression. Instead of two hydrogen bonds holding A and T together, DAP introduces a third hydrogen bond with T, making DNA containing DAP relatively stronger (Figure 4). Exchanging DAP for the A base pair essentially strengthens the structure without affecting base pair sequence and thus information transmission. This slight change in structure has enormous consequences on the function of DNA and future applications. Consider adding an extra zip tie to a bike bell or basket and how that might alter the appearance of your bike. Or how would you ride a bike differently if the frame was welded of heavier steel rather than lighter aluminum or if much stronger cantilever breaks replaced your standard clamping brakes?