DNA & RNA: The foundation of life on Earth

Stylized representation of a DNA double helix   Image: videohive.net

DNA and RNA are the foundation molecules of life on Earth. Without DNA and RNA, we would have a completely different kind of life (if we had it at all).

DNA (deoxyribonucleic acid) is a polymer, a long chain of repeating subunits called nucleotides, which are, in turn, made of a nucleic acid base, a sugar called ribose, and a phosphate group that links the sugars to form the "backbone" of the chain. Except in rare circumstances, two DNA strands, a kind of "mirror image" of one another, are always found together, twisted into a double helix.

The main purpose of DNA in cells is information storage. A DNA chain carries in its sequence of bases the code for the sequence—the blueprint—of everything that is manufactured by the cell, including RNA molecules and proteins.

RNA (ribonucleic acid) is a simpler beast with a more complicated role. It, too, is a polymer very similar to DNA, but it is generally only found as a single chain or "strand." RNA molecules can adopt a number of 3-D shapes that, like proteins, can give them unique functions.

RNA is used by cells as a structural element of protein complexes, as an enzyme (a ribozyme), and a carrier of information (mRNA, tRNA), and by some viruses as the main storehouse of genetic information.

RNA is thought to have appeared first in the evolution of life, before DNA, and some molecular biologists speculate about an "RNA world" of long ago.

In this section, we'll build DNA and RNA chains from their smaller components, then explore their roles.

Bases: the pyrimidines

The core components of DNA and RNA are the nucleotide bases. These come in two categories, the pyrimidines and the purines. The pyrimidines are six-membered carbon-nitrogen rings with various side groups that include thymine (abbreviated T), cytosine (C) and uracil (U).

In a sense, DNA and RNA molecules are extended chains of linked bases. They are linked to a backbone of alternating phosphate and sugar molecules, as we shall see.

The base cytosine is found in both DNA and RNA, but while DNA incorporates the base thymine, RNA uses the base uracil in its place. The two differ by the methyl (CH3) group, which is a hydrogen in uracil.

The yellow hydrogens (H) are where we will link the sugar ribose (or deoxyribose) later.

Bases: the purines

The two purine bases, composed of linked six- and five membered carbon-nitrogen rings, are found in both DNA and RNA.

The yellow H-atoms are removed for binding to the sugar ribose (in RNA) or its derivative deoxyribose (in DNA).

The nitrogen atoms in both purines and pyrimidines are crucial for hydrogen bonding (H-bonding) between bases, and that H-bonding is critical for formation of the DNA double helix.

All nucleotide bases are planar (flat) molecules. That geometry has an important consequence for the structure of long DNA and RNA chains.

About molecular drawings

The molecular models I drew above are "ball & stick" models. More frequently, you will see the DNA bases represented in the shorthand form below, in which most carbons are implied. In these diagrams, every unlabeled vertex, like the one just below the H at the "top" of cytosine, is a carbon atom. Double lines represent double

bonds; single lines are single bonds. Almost always, carbon atoms must form four bonds.

The bases on the top row are pyrimidines (one ring) and those on the bottom are purines (two rings). The ring structures here are referred to as heterocyclic compounds because the ring is composed of both carbon and nitrogen


Ribose is a five-carbon sugar that is a crucial part of any DNA or RNA chain. It's what links each base to the phosphate backbone that links up the chain.

Ribose is what distinguishes RNA (ribo-nucleic acid) from DNA. DNA contains ribose sugars from which one of the hydroxyl (OH) groups has been removed to form deoxyribose. DNA is deoxyribo-nucleic acid.

The yellow OH group detaches to form the bond to a base to form a nucleoside, and the yellow H is the site of bonding of the sugar to the phosphate backbone.

Formation of a nucleoside

A nucleoside is formed when a ribose or deoxy-ribose are linked in a dehydration reaction (a reaction that liberates a water molecule in the process of forming a new bond). Here is a very simplified version of the reaction that forms deoxyribo-cytosine, or cytosine nucleoside. The actual reaction requires a few enzymes.

Nucleoside phosphates

Now to complete the building blocks of DNA and RNA we need to add the phosphate (PO43-) group. To build a DNA or RNA polymer or strand, nucleosides are linked through the phosphate group. Two examples of nucleoside phosphates are shown below.

On the left is the DNA building block deoxyribose adenine phosphate and on the right is the RNA subunit ribose uracil phosphate. By changing the base we can derive each of the three other nucleoside phosphates. The hilighted oxygen atom is the site of bonding to the next nucleoside in the chain.

Putting it all together: the phosphate backbone

A (very) short DNA strand, the top is the 5' end.

Now let's put those nucleotides together to make a chain. I'll stick with DNA for now and we'll get back to RNA later.

All that's required to link nucleotides is to form the continuous backbone of the chain by forming a series of —C—O—P—O—C— ... bonds, called phosphodiester bonds between the ribose sugars of the nucleosides.

These bonds are formed in a series of enzyme-catalyzed reactions that actually degrade the di-phosphate and tri-phosphate form of each nucleotide (below) to derive the monophophate form and recover the energy from those broken bonds to drive the reaction.

Chains of nucleotides of RNA and DNA can be between 10 and several million nucleotides!

Remember in staring at such a diagram, that every unlabeled vertex between bonds is a carbon atom.

The unique geometry of the deoxyribose sugar forces a twist in long chains of DNA, leading to the helical structure we see in a complete DNA strand consisting of two of these chains coupled together. More on that below.

DNA and RNA strands have a direction

There is a labeling convention for the carbons of sugars like ribose. I won't go into exactly how it works here; suffice to say that the carbons are labeled 1' (read "one-prime"), 2', 3' and so on as shown.

The backbone phosphates of DNA and RNA bind to the 3' carbon of one ribose and to the 5' carbon of another, so a DNA or RNA strand has a direction. We generally read and write the sequence of bases in the 5' to 3' ("5-prime to 3-prime") direction. Most of the biochemical processes that happen to DNA and RNA, like replication or reading of the sequence information, happen in this direction, too.

DNA and RNA strands are polymers composed of the purine or pyrimidine bases A, C, G and T (or U in RNA), bound to the 1' carbon of the 5-carbon sugar ribose. The sugar-base pair is called a nucleoside. Each nucleoside is bound to another by a phosphate through phosphodiester bonds connecting the 5' carbon of one ribose to the 3' carbon of the next.

Base pairing in DNA

In almost all situations, DNA strands occur in complementary pairs that stick to each other through specific base-to-base hydrogen bonds. It turns out that the bases nature has selected for use in DNA fit perfectly to one another in specific pairings: One purine and one pyrimidine, A to T and G to C.

The figure below shows the pairings. The lone pairs of oxygen and nitrogen atoms act as H-bond acceptors for the protons of amine groups of the bases. Adenine and thymine share a pair of H-bonds and Guanine-cytosine pairs share three bonds. These are the only base-pairs that ever occur in DNA: A-T and G-C.

Complementary strands

DNA is a very complicated molecule and often we're just interested in the sequence of bases in its strands. A common representation of the sequence of both complementary strands looks like this:

Notice that every T is paired with an A and every G is paired with a C.

3-D representations of DNA

There are many ways to represent the 3-dimensional structure of DNA. Short lengths of DNA are shown below in a variety of forms. On the left is a ($4000 !) ball & stick model that decorates Sheldon and Leonard's apartment in the CBS TV series The Big Bang Theory. The black-and-white space-filling drawing may be the most accurate representation because it more faithfully represents the space taken up by the electron clouds of the atoms.

In that representation it's easy to see that the DNA double helix possesses two grooves; the smaller is the minor groove and the larger is the major grooove. The stick model with the black background is typical of a computer 3-D model used to examine structure closely. Notice in all models that the base pairs are coplanar. The simple representation on the right distills all of the detail down to its essence: two twisted strands attached by complementary bases.

Why the twist?

Figure: Principles of Biochemisrty 2nd Ed.; Lehninger et al. (1993).

Double-stranded DNA takes on the form of a double helix (a 3-dimensional spiral, or rather two intertwined 3D spirals). If we look at it in the 5' to 3' direction, it's a right-handed helix. The right hand rule works like the sketch on the right: Point your thumb along the 5'-3' direction and the curvature moves upward in the direction that your fingers curl around.

DNA takes on this form for a variety of reasons, all of which have to do with intermolecular forces. The phosphate/ribose backbone of DNA is hydrophillic (water loving), so it orients itself outward toward the solvent, while the relatively hydrophobic bases bury themselves inside. Additionally, the geometry of the deoxyribose-phosphate linkage allows for just the right pitch, or distance between strands in the helix, a pitch that nicely accommodates base pairing. Lots of things come together to create the beautiful right-handed double-helix structure.

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