1. Introduction: DNA and RNA are life’s molecules of information

Nucleic acids — DNA and RNA — are the fourth class of macromolecules.

1a. DNA Overview 

DNA stands for deoxyribonucleic acid. It’s the molecule of heredity. It’s the stuff that genes are made of.

DNA is the form in which hereditary information — what gets passed from parents to offspring — is chemically encoded. In much the same way that the computer that you’re using is following instructions from a computer program and translating those instructions into letters and images on the screen, cells follow DNA instructions and respond by making two other types of molecules: RNAs and proteins. These molecules, in turn, control cellular activities.

Turning to a different analogy, you can think of DNA as a recipe that tells cells what RNAs and proteins to make. In multicellular beings like ourselves, DNA also guides the pattern of development by which a fertilized egg develops into a multicellular organism.

1b. RNA Overview

RNA stands for ribonucleic acid. In certain viruses — including SARS-CoV-2 and HIV — RNA encodes genes. But for the most part, RNA’s role is to act as an intermediary between the DNA that we inherit and the protein that makes us up.

Here’s an example. About 1 in every 2500 babies born to North Americans of European ancestry inherit a disease called cystic fibrosis. Cystic fibrosis involves the buildup of thick, sticky mucus in the lungs and other organs. This causes problems with breathing and sets the stage for chronic lung infections. There are other effects throughout the body. The overall result is a significantly shortened lifespan.

Cystic fibrosis is caused by a mutation in the CFTR gene. CFTR codes for a membrane protein. In people with for cystic fibrosis, the CFTR gene is mutated and carries faulty instructions. As a result, the membrane protein doesn’t work.

We can follow the flow of information in the diagram above. In a child who inherits the disease, the defective DNA instructions are in the nucleus (“2”) of every one of their cells, encoded within their DNA (at “3”). In the cells that make up this child’s lungs (where cystic fibrosis has its most significant effects) that DNA is transcribed into RNA, shown at “5.” That RNA leaves the nucleus and makes its way to the cytoplasm (“6”). In the cytoplasm, the information in the RNA is translated into protein (“8”) by a molecular machine called a ribosome (“7”). That protein, however, because it’s the product of a mutated DNA recipe, won’t work correctly. When it makes its way to the cell membrane (“1”), it won’t correctly perform its function, which is to allow chloride ions to diffuse out of the cell through the cell membrane. The accumulation of chloride ions in the cell has the effect of drawing water away from the cell’s exterior. This causes any mucus that’s been secreted from that cell to become thick, resulting in the symptoms of cystic fibrosis.

While RNA can store and transfer information, it can also be a molecule of action. Some RNAs, like the RNA that makes up about half of a ribosome, can catalyze chemical bonds, giving them an enzyme-like function. Other types of RNA play key roles in controlling gene expression, determining when DNA information gets transcribed into RNA, and when RNA gets translated into proteins.

Because RNA can act as both information and action, it’s a strong candidate for having served as part of the first living systems that originated about 3.8 billion years ago, when life first began — a topic that we’ll explore when we learn about the origin of life in Unit 7 of this course.

2. The Monomers of Nucleic Acids are Nucleotides

Both RNA and DNA are composed of monomers called nucleotides.

An RNA nucleotide	A DNA nucleotide

Note: Use this link to review carbon numbering. Use this link to review how to read structural formulas.

1. DNA and RNA nucleotides are both built around 5-carbon sugars (see region “2” in the table above). The sugar in an RNA nucleotide (the one on the left) is called ribose. The sugar in DNA is deoxyribose. If you look at the sugars, you can see how these names work. Ribose has hydroxyl groups (—OH) attached to its 3′ and 2′ carbons. In deoxyribose, the 2′ carbon has a hydrogen atom in place of the hydroxyl group. With one less oxygen, the name changes from ribose to deoxyribose.
2. Attached to the 5′ carbon in both deoxyribose and ribose is a phosphate group (at “1”). The phosphate group is what makes these molecules acidic (the “A” in both DNA and RNA stands for “acid”). The negative charges on the oxygens are what’s left after protons have been donated to the surrounding solution.
3. Attached to the 1′ carbon is one of four nitrogenous bases. These bases are the informational part of DNA and RNA, and allow these molecules to encode information. They’re bases because they have an amino group attached to them (at “4”), and that amino group absorbs protons from a solution, raising the pH. They’re nitrogenous because they have lots of nitrogen atoms.
   1. The bases in DNA are adenine, thymine, cytosine, and guanine, represented by the letters A, T, C, and G.
   2. The bases in RNA are adenine, uracil, cytosine, and guanine, represented by the letters A, U, C, and G.

Here are the four DNA nucleotides. Note that adenine and guanine have double-ring nitrogenous bases, while thymine and cytosine have single-ring nitrogenous bases.

The four DNA nucleotides
Bases with two nitrogen rings	Bases with one nitrogen ring

Here, for comparison, is an RNA nucleotide with uracil. Note the similarity between uracil’s nitrogenous base and the nitrogenous base in thymine.

In most AP Bio courses, you won’t need to be able to identify which nitrogenous base is which. But you should be able to identify a nucleotide’s general structure, and differentiate between nucleotides and the other monomers you’ve met: monosaccharides, amino acids, and fatty acids.

3. DNA, RNA, and Nucleotides Checking Understanding

4a. DNA and RNA Structure

Both DNA and RNA are nucleotide polymers.

These polymers, at their most basic level, consist of strands of nucleotides connected in a linear sequence to one another by covalent bonds. You can see this in the diagram to your right, which shows all four of the RNA nucleotides chained together. Note that the sequence can be any combination, including repeats of the same nucleotide: that’s how nucleotides store and transfer information. In the same way that the letters of the English alphabet spell out words, the letters in DNA or RNA spell out proteins. We’ll learn the details of how this coding works in AP Bio Unit 6 of this course.

The covalent bonds connecting the nucleotides have the following structure: the 5′ carbon of one nucleotide connects to that nucleotide’s phosphate group, and then that phosphate group connects to the 3′ carbon on the sugar in the next nucleotide. The bond connecting one nucleotide to the next is called a sugar-phosphate bond.

In a DNA or RNA polymer, the connected sugars and phosphates make up a sugar-phosphate backbone. 

Another level of structure emerges from the shape and chemistry of the nitrogenous bases on DNA or RNA.

In DNA, the nitrogenous base adenine has a shape that’s complementary to the base thymine, and the base cytosine has a shape that’s complementary to guanine. Things that are complementary fit together, like the way that a key fits into a lock, a hand fits into a glove, etc.

As we’ll see throughout this course, complementarity is one of the most important phenomena in biology, and it’s the basis of many structure-function relationships. Complementarity explains how enzymes work, how chemical signals bind to receptors, and how the immune system recognizes and fights off invaders. Note the spelling. When two things are complementary, they fit together. When somebody says something that’s complimentary (with an “i”), they’ve said something nice.

In addition to their complementary shape, polar functional groups on these bases will form hydrogen bonds with one another. Three hydrogen bonds form between cytosine and guanine, while two bonds form between adenine and thymine.

Hydrogen bonds between complementary bases in DNA

The dotted lines between complementary bases indicate hydrogen bonds
Guanine-Cytosine	Adenine-Thymine

Though it’s not shown in the diagram above (and often not shown in published diagrams) complementarity between bases and hydrogen bond formation only happens when the nucleotides are positioned upside-down relative to one another, as shown below.

Adenine and Thymine	Guanine and Cytosine

The result of this complementary base pairing is that DNA is typically double-stranded. Because the nucleotides in the two strands can form hydrogen bonds with one another only when they’re oriented upside-down relative to one another, the overall arrangement of the molecule is said to be antiparallel. 

The bond angles between the sugar and phosphates twist DNA into its famous double helix formation, as shown on the right.

1. Deoxyribose
2. Phosphate
3. Sugar-phosphate (covalent) bonds
4. Nitrogenous bases
5. A nucleotide
6. Hydrogen bond
7. Sugar-phosphate backbone.

 

4b. Video: Seven Things to Know about DNA Structure

5. DNA Structure Quiz

 

6. Final Points: Introducing DNA Replication, RNA synthesis, and Ribozymes

6.a. DNA replication

DNA’s structure provides a way for DNA to be replicated. That allows DNA to be passed from one generation to the next and passed from one cell to its daughter cells as an organism grows, develops, and repairs itself.

Here’s a big picture view of how DNA replication happens. Note that you’ll explore the details of replication in Unit 6 of this course.

1. In a series of reactions catalyzed by a team of enzymes, the two strands of DNA separate.

2. With bases exposed, each single strand serves as a template for the synthesis of a new strand. Following the base-pairing rules, new complementary nucleotides form hydrogen bonds with nucleotides on the template strands.

3. Another team of enzymes seals covalent bonds between the sugars and the phosphates of adjacent nucleotides.

The enzymes that carry out DNA replication (and which transcribe RNA from DNA) can only add new nucleotides at the 3′ end of a growing strand. Later on in the course, we’ll see how this structures how DNA replication occurs. We’ll also see how this might be part of the reason why we’re not immortal, and why we succumb to diseases like cancer.

6.b. RNA Synthesis/transcription

Complementary base pairing is also an essential part of RNA’s structure and function.

To begin with, the bases in RNA can form complementary base pairs with the bases in DNA. During a process called transcription, an enzyme called RNA polymerase opens up a stretch of DNA and uses the DNA as a template for making RNA. As shown in the table below, the base-pairing rules between RNA and DNA are almost the same as those used during DNA replication.

DNA Base	Adenine	Thymine	Cytosine	Guanine
RNA Complement	Uracil	Adenine	Guanine	Cytosine

Here’s a diagram showing the transcription of RNA from DNA.

Note how in transcription, as with DNA replication, new RNA nucleotides can only be added at the 3′ end of a growing nucleotide strand.

6.c. RNA’s 3-D Structure; Ribozymes

Base pairing plays a role in RNA structure in yet another way. RNA can serve as an action molecule because it can fold into complex three-dimensional shapes. This folding emerges from hydrogen bonding between nucleotides in the same molecule of RNA.

The molecule to the left is a transfer RNA. The letters represent the nitrogenous bases (A, U, C, and G) in an RNA nucleotide, with the sugars and phosphates left out (the letters in blue represent modified nucleotides). tRNA’s role is to bring amino acids from the cytoplasm to the ribosome. Its cloverleaf shape emerges from hydrogen bonds that form between adenine/uracil and guanine/cytosine pairs which bond with one another with enough force to stabilize the molecule into this specific shape.

Other RNAs act as ribozymes: biological catalysts that are made of RNA (the “zyme” part of ribozyme refers to enzymes).

In biological systems, catalytic ability emerges from a molecule’s shape. In enzymes (which are proteins), that shape emerges from secondary, tertiary, and quaternary levels of structure, all of which are based on chemical interactions between the amino acids in a polypeptide. In the case of ribozymes, the interactions are from hydrogen bonds between RNA nucleotides. These can result in shapes as complex as the ones shown above, all of which give rise to these molecules’ catalytic properties.

7. Nucleic Acids: Checking Understanding

The purpose of this tutorial was to give you an overview of nucleic acids. You’ll explore the roles of DNA and RNA in gene expression in greater detail in Unit 6 of this course. But for now, let’s consolidate everything we’ve learned by taking a quiz.

What’s next?

• Proceed to the Unit 1 Cumulative Flashcards and Quizzes, where you can review all of the biochemistry you’ve learned in this unit.