DNA, RNA and genetic information

Your body contains many cells. A cell is a small living unit. A membrane separates its inside from its surroundings and controls what crosses it; it is not a solid wall that nothing can pass through. Inside, molecules take part in reactions that make new material or release usable energy, for example by breaking down sugar. Other molecules help move substances around. A molecule is a group of connected atoms; atoms are very small building units of matter, and a chemical reaction rearranges them into different combinations. For this chapter, keep three things in view: a cell, its membrane, and the molecules that do its work.

Many of the molecules doing this work are proteins. A protein contains one or more chains of amino acids, which are small molecular building units. The order of those units affects how the chain folds and what the protein can do. We therefore need more than a supply of raw material: the cell also needs a way to specify useful arrangements of that material.

The order we need to preserve brings us to DNA, whose full name is deoxyribonucleic acid. It is a chemical substance that stores biological sequence information. Calling it information can feel abstract for now. Later we will follow the order of its units and see how other molecules use that order; for the moment, let us locate the material itself. Most DNA in the human cell model is in the nucleus, a compartment with its own surrounding membrane. A small amount also occurs in mitochondria; our example follows the nuclear DNA.

Enlarging a tiny structure can create a new difficulty: we can see more detail, but lose track of where it came from. A cell and a DNA molecule differ enormously in size, so we need several changes of magnification. Find the orange selection before pressing Next. That colour keeps hold of the same selected material while the view changes. If the enlarged view becomes unfamiliar, glance at the small context drawing; it keeps the earlier location in view for us.

The purple threads inside the nucleus represent chromatin. Chromatin means DNA together with proteins associated with its organisation. The orange section is a selected part of those same purple threads. When we later distinguish DNA from the proteins around which it is wrapped, we are revealing the composition of chromatin, not finding a second, unrelated material concealed inside it.

Look back at the wrapping unit. Its name is a nucleosome: DNA wrapped around a core of eight histone proteins. A histone is a kind of protein, not another name for DNA. Many such units help organise a long DNA molecule. The model spreads units apart so that their connections remain visible; chromatin in a cell is not always a uniform, regularly coiled fibre.

DNA and chromosome are also not interchangeable names. A chromosome is an organised unit of this DNA–protein material. Before DNA is copied, one human nuclear chromosome contains one long double-stranded DNA molecule with associated proteins. It remains a chromosome when it is spread out and difficult to distinguish under a microscope; it does not have to look like an X.

For counting, take a typical human body cell with two sets of chromosomes: 23 from each parent, giving 46 in total. This is our example, not a claim about every human cell. Egg and sperm cells normally have 23; mature human red blood cells have no nucleus. Some other specialised cells also differ from this example.

Before an ordinary cell division, each DNA molecule is copied. The two copies remain associated in two sister chromatids. A chromatid is one of these DNA-and-protein copies. The sisters are held together until they separate; the constricted centromere region is the familiar joining region in an X-shaped drawing. Each sister contains a complete double-stranded DNA molecule. The two sides of the X are therefore not the two strands of one DNA double helix.

While the centromere holds the sisters together, they are one object, so we still count the pair as one replicated chromosome. DNA amount has doubled, but the chromosome count has not yet doubled. Once the sisters separate, each is counted as a chromosome in its own right. In ordinary division, the two daughter cells each receive one copy of every chromosome.

The sketch above follows one chromosome. To see all of them, return to the 3D model in chapter 2 and press “Compare the dividing-cell chromosomes”: that division view shows 46 replicated chromosomes, containing 92 DNA molecules. It arranges them with space between them so that you can inspect the count; it is not their random live arrangement or a metaphase plate. Their X-like shape represents condensed replicated chromosomes, not the special identity of the X sex chromosome. Nuclear-envelope breakdown and chromosome condensation occur over stages, not as one instantaneous switch.

We now return to the DNA molecule itself. Matter is made from atoms, and chemical bonds can join atoms into molecules. A nucleotide is one repeating unit of a DNA strand. It has three connected parts: a phosphate group, a sugar called deoxyribose, and a base. Here “base” names one part of a nucleotide; it does not mean the whole nucleotide.

DNA uses four usual bases: adenine (A), thymine (T), guanine (G) and cytosine (C). We use the letters because it is easier to follow a sequence of twelve letters than twelve long chemical names. Repeated sugar–phosphate connections make the backbone of a strand; each sugar also carries its base. Changing the letter changes the base, not the basic arrangement of the entire backbone.

Put a second strand beside the first. In the usual DNA pairing, A pairs with T, and G pairs with C. These complementary pairs have compatible shapes and arrangements of atoms that can form hydrogen bonds. Hydrogen bonds are attractions between particular groups of atoms. They differ from the covalent bonds that hold each strand’s backbone together.

A–T normally forms two hydrogen bonds and G–C three. But it would be incomplete to say that hydrogen bonds alone hold DNA in its familiar form. Neighbouring bases also stack against one another inside the helix, and these stacking interactions contribute substantially to its stability. In the model, inspect both across a pair and along the stack.

Some parts of a molecule really are approximately flat: the rings of these bases are an example. Other parts extend in three dimensions. A faithful model should retain both facts. Drag the nucleotide to inspect its puckered sugar and spatial phosphate group, then compare that with a base ring. The balls and sticks are a convention for atoms and bonds, not a photograph of their surfaces.

The sugar in each nucleotide has numbered carbon atoms. The labels $5'$ and $3'$ refer to two of those positions, read “five-prime” and “three-prime”. Successive nucleotides connect through a phosphate linking the $3'$ position of one sugar to the $5'$ position of the next. The resulting strand has two chemically different ends. The prime mark distinguishes sugar-atom numbering; it is not a derivative, a unit of time or a length.

DNA’s two strands run in opposite directions. If the upper strand runs from $5'$ on the left to $3'$ on the right, the lower partner runs from $3'$ on the left to $5'$ on the right. This is called antiparallel. It describes the chemical orientation of two strands, not a claim that the strands are moving in opposite directions.

Use the same twelve positions as the structure model. At each position, choose the partner directly underneath the existing base. Start with position 1: the upper base is $A$, so the lower one must be $T$. At position 2 the upper base is $T$, so the lower one must be $A$. We are recording paired positions from left to right; we are not yet rewriting the lower strand in its own $5'-to-3'$ reading order.

When a DNA sequence is written on its own, it is usually written from $5'$ to $3'$. Finding the complementary strand means choosing the matching base at every position. That gives us the bases, but their displayed order may run from $3'$ to $5'$. To write this strand in $5'$-to-$3'$ order, we reverse the displayed order when needed. For these twelve positions, the lower row reads 3′–TACGCATGCGAT–5′ from left to right. Read from position 12 back to position 1, it is 5′–TAGCGTACGCAT–3′. This changes the way we write the sequence, not the molecules themselves.

The sugar–phosphate framework repeats, but the order of bases can vary. ATG and AGT contain the same three letters in different orders. Molecules that interact with these stretches can distinguish that order. Thus a sequence can affect what a cell makes and when it makes it. Information here means an arrangement that can be copied and used through molecular interactions; the letters do not know what they mean.

A gene is a DNA sequence used to make an RNA molecule with a role in the cell. Some of these RNA molecules carry the instructions for a protein: the cell reads the relevant part of the RNA to choose the amino acids. Other RNA molecules do their work without being used to make a protein. We will meet two examples, tRNA and rRNA, shortly. So “every gene makes a protein” would leave out an important group of genes.

Nor is every part of DNA a protein-coding sequence. Some regions help regulate when genes are used; other regions have structural or other roles, and not every region’s role is fully understood. The complete collection of an organism’s DNA is its genome. A chromosome is one organised part of that collection, not one gene; many genes and other sequences can lie along it.

The twelve-base example above was invented to practise structure and pairing. It is not presented as an entire working human gene. Having the letters A, T, G and C, or even a short familiar sequence, is not enough by itself to specify a complete gene with all the signals needed for its use.

Return to our first question: how can two daughter cells receive the DNA information? Simply cutting one molecule in half would give each cell only part of its sequence. Instead, before division, the cell builds a copy. Replication is the name for this copying of DNA into DNA.

Complementary pairing provides a way to do this. Separate the two strands without cutting either backbone. Each exposed old base now constrains which new base should be placed beside it. An old A calls for a new T; an old T calls for a new A; G and C similarly choose one another. The old strand serves as a template: a pre-existing sequence used to determine the new sequence.

In the model, purple backbones mark material that already existed and blue backbones mark newly made material. Base colours still identify A, T, G or C. Follow both old strands all the way to the end. Do not let “two new DNA molecules” make you assume that every atom in both products must be new.

At the end, each double helix contains one old strand and one new strand. That is semiconservative replication: half of each product’s two-strand framework is retained from the original molecule. The old strand supplies the sequence pattern; free nucleotides supply new material. The old bases do not split into duplicate bases or turn into the new strand.

Real cells need more than a pairing rule. This paragraph and the next add detail; skip them on a first read if you like. A helicase is a molecular machine that helps separate the strands locally. A DNA polymerase is an enzyme that adds suitable nucleotides to a growing DNA chain. An enzyme is a molecule that helps a chemical reaction occur; many enzymes are proteins. DNA polymerase needs an existing starting end, supplied through a short primer, and extends the new chain at its $3'$ end. Therefore the new DNA grows in the $5'-to-3'$ direction.

An opening region advances along the old DNA; its branching end is called a replication fork. The old strands point in opposite directions, so the two new strands cannot both grow the same way. One new strand extends along the fork’s advance. The other is made in short stretches pointing away from that advance. Every short stretch still grows $5'$ to $3'$. After the primers are removed and replaced with DNA, DNA ligase seals remaining backbone breaks. Both products become continuous strands; the second strand is not synthesised backwards.

Our animation isolates pairing and inheritance of old material. Its straightened view and simultaneous filling of displayed positions are drawing choices, not a full timing diagram for these enzymes. It also assumes correct copying. Cells have proofreading and repair mechanisms, but errors can sometimes remain; a change in DNA sequence is called a mutation.

We now have enough information to separate two processes that can otherwise look similar. Replication copies DNA into DNA so that the genome can be passed on during division. Transcription makes RNA using a selected DNA region as a template. In transcription, only one of the two DNA strands is read for a particular RNA product, and the original DNA is retained.

RNA means ribonucleic acid. Like DNA, it is built from nucleotides, but its sugar is ribose rather than deoxyribose, and its usual bases are A, U, G and C. U is uracil. It pairs with a DNA template’s A during transcription, where a DNA copy would instead use T. RNA is commonly single-stranded, but parts of a strand can pair with other parts and fold into a three-dimensional shape.

Translation is a third process: the sequence of an mRNA is used to assemble an amino-acid chain. mRNA means messenger RNA. The message supplies an order, while amino acids supply the material of the chain. The mRNA does not turn into protein. We will now inspect the RNA message, the tRNA adaptors that carry amino acids, and the rRNA inside the ribosome where the chain is assembled.

For this next workshop we deliberately change to a different short example. The earlier ATGCGTACGCTA was for DNA pairing. Here, after RNA processing, the message is AUG GCU UUU UAA. It is chosen so that we can follow three amino acids and a stop signal without hiding steps in a long sequence. These two sequences are separate teaching examples, not successive states of the same molecule.

The explanation below introduces proteins and RNA. These objects will help us understand what mRNA, tRNA, rRNA and the assembly cycle do. Each chapter has its own stable view. Play shows only the selected step and stops when it ends; Next lets you decide when to continue. Rotate or zoom when you want to inspect a structure, and use Restore view if you lose your place.

We can now test what the order of bases changes. Keep the same short message from the RNA workshop: AUG GCU UUU UAA. Here we show the corresponding coding DNA, $5'-ATG$ GCT TTT $TAA-3'$. The coding strand has the same sequence as the RNA except that DNA uses $T$ where RNA uses $U$. It is the opposite DNA strand that serves as the template during this transcription.

A codon is a group of three RNA bases read in a defined reading frame. A reading frame tells us where to start dividing the sequence into groups of three. We keep the first AUG fixed as the start in this invented example, then read consecutive groups without skipping or overlapping letters. The standard genetic code maps each group to an amino acid or a stop signal. More than one codon can specify the same amino acid.

Select an example, or change one of the coding-DNA letters below. A base substitution replaces one letter with another without changing the number of letters. The paired template and resulting RNA update with it. Read down a column: DNA sequence, RNA codon, then the resulting amino acid. After the first stop codon, later groups remain in the message but are not added to this chain.

A synonymous change leaves the amino-acid sequence unchanged in this reading frame. It does not establish that the change has no effect anywhere in a living cell: RNA processing, stability or translation can also matter. A different amino acid likewise does not by itself prove disease. This small model reports sequence consequences under the stated start and reading-frame assumptions; it does not predict a person’s health.

Return to the cell at the beginning. Its purple chromatin is DNA together with proteins. DNA’s bases form a sequence, complementary pairing makes that sequence copyable, and replication preserves one old strand in each product. A selected DNA sequence can also be transcribed into RNA. Some RNAs carry messages; others act as adaptors or form part of the machinery that uses those messages.

Try the questions before opening the explanations. A useful answer says which material is present, what changes, and what remains. Naming a process without tracing the material is not yet enough to explain it.