Chromosomes and DNA.

Every instruction needed to build and run a living body is written in one long molecule — DNA — coiled inside the cell's nucleus. This chapter follows that molecule from the way it is packed into chromosomes, through the elegant double helix, to how it copies itself and how its message is read out to make the proteins that run the cell.

1 · The hereditary material is DNA

The nucleus of a cell carries the genetic information that controls every activity and is passed from parent to offspring. That information is stored in deoxyribonucleic acid (DNA). A gene is a length of DNA that codes for one polypeptide (one protein), and the complete set of an organism's DNA is its genome.

Inside the nucleus the DNA is not naked — it is wound around proteins to form a thread called chromatin. When a cell is about to divide, this chromatin coils up tightly into the compact, visible bodies we call chromosomes.

2 · The chromosome — packing the DNA

A single human cell holds about two metres of DNA, yet the nucleus is only a few micrometres across. To fit, the DNA is folded and packed in stages using basic (positively charged) proteins called histones.

• The DNA double helix wraps about twice around a core of eight histone proteins, forming a bead called a nucleosome.
• A string of nucleosomes looks like "beads on a string", and this coils further into a thicker chromatin fibre.
• The fibre loops and supercoils more and more until, at cell division, it becomes a fully condensed chromosome.

A condensed chromosome that has already been copied consists of two identical chromatids (sister chromatids) joined at a narrow waist, the centromere. The histone packing both shortens the DNA so it can be moved cleanly during division and helps control which genes are switched on.

Human body cells are diploid (2n = 46) — 23 pairs of homologous chromosomes, one of each pair from each parent, including the sex chromosomes (XX female, XY male). Gametes are haploid (n = 23).

3 · The structure of DNA — the double helix

In 1953 James Watson and Francis Crick (using Rosalind Franklin's X-ray work) showed that DNA is a double helix — two strands twisted around each other like a spiral staircase. The repeating building block of each strand is a nucleotide.

A single nucleotide has three parts:

• a pentose sugar — deoxyribose (5 carbons);
• a phosphate group;
• one nitrogenous base.

There are four bases, in two chemical families:

• Purines (double-ring): adenine (A) and guanine (G).
• Pyrimidines (single-ring): thymine (T) and cytosine (C).

Nucleotides join into a strand when the phosphate of one links to the sugar of the next, building an alternating sugar–phosphate backbone (held by phosphodiester bonds). The bases stick inward from this backbone.

Complementary base pairing

The two strands are held together by their bases, and the pairing is strict — this is the most important rule in the whole chapter:

A purine always pairs with a pyrimidine, so the two strands stay a constant width apart. Because the pairing is fixed, the two strands are complementary — knowing one strand tells you the other exactly. The bonds joining the pairs are weak hydrogen bonds: individually weak (so the strands can be "unzipped" for copying and reading) but, in their millions, strong enough to hold the molecule together.

Antiparallel strands

The two backbones run in opposite directions — they are antiparallel. One strand runs 5′ → 3′ while its partner runs 3′ → 5′ (the 5′ and 3′ refer to the carbon atoms of the sugar at each end). This opposite orientation matters greatly during replication.

4 · DNA replication — making an exact copy

Before a cell divides it must duplicate all its DNA so each daughter cell gets a full set. The method is semi-conservative replication: the two strands separate, and each old strand acts as a template for building a new partner. Every new DNA molecule therefore has one old (conserved) strand and one new strand — proven by the classic Meselson–Stahl experiment.

The steps, in order:

1. The enzyme helicase breaks the hydrogen bonds and unwinds and unzips the double helix, opening a Y-shaped replication fork.
2. Free nucleotides in the nucleoplasm pair with the exposed bases by the complementary rule (A with T, G with C).
3. The enzyme DNA polymerase joins these nucleotides into a new strand, building the sugar–phosphate backbone, and also proof-reads for errors.
4. The two new double helices rewind. Each is identical to the original.

5 · RNA and its types

RNA (ribonucleic acid) carries DNA's message out to where proteins are made. It differs from DNA in three ways: it is usually single-stranded, its sugar is ribose (not deoxyribose), and it uses the base uracil (U) in place of thymine (so U pairs with A).

There are three kinds of RNA, all needed for protein synthesis:

• Messenger RNA (mRNA) — copies the gene's message from DNA and carries it to the ribosome.
• Transfer RNA (tRNA) — a small clover-leaf molecule that fetches a specific amino acid and reads the mRNA by its anticodon.
• Ribosomal RNA (rRNA) — together with protein, builds the ribosome, the workbench where the polypeptide is assembled.

6 · Protein synthesis — reading the code

A gene's job is to specify a protein. The information flows in one direction — the central dogma:

① Transcription (DNA → mRNA, in the nucleus)

The DNA unzips over the gene, and the enzyme RNA polymerase reads one strand (the template strand) and builds a complementary strand of mRNA using the base-pairing rule — but with U opposite A. The finished mRNA peels off and leaves the nucleus through a nuclear pore, travelling to a ribosome in the cytoplasm.

② The genetic code

The mRNA is read in groups of three bases. Each triplet is a codon and stands for one amino acid. With four bases there are 4³ = 64 codons for the 20 amino acids, so the code is described as:

• Triplet — three bases per codon.
• Universal — almost the same in every living organism.
• Degenerate — most amino acids have more than one codon.
• Non-overlapping — read three at a time, in a fixed reading frame.

One codon, AUG, is the start codon (it also codes for methionine); three codons (UAA, UAG, UGA) are stop codons that end the chain.

③ Translation (mRNA → polypeptide, at the ribosome)

The ribosome clamps onto the mRNA at the start codon and moves along it codon by codon. For each codon a matching tRNA arrives — its anticodon is complementary to the codon — carrying the correct amino acid. The ribosome joins each new amino acid to the last by a peptide bond, so a polypeptide chain grows. When a stop codon is reached, the finished chain is released and folds into a working protein.

7 · The cell cycle & chromosomes (briefly)

All of this happens within the cell cycle — the orderly sequence a cell passes through between one division and the next. It has two main parts:

• Interphase — the long growth-and-preparation stage (G₁, then S phase where DNA replicates, then G₂). The chromosomes are uncoiled as chromatin so the DNA can be read and copied.
• Mitotic (M) phase — mitosis (nuclear division) followed by cytokinesis (the cell splits). Now the chromatin condenses into visible chromosomes so the copied DNA can be shared out exactly.

The link to this chapter is direct: DNA must be replicated in S phase (Section 4) and then packed into chromosomes (Section 2) so that mitosis can deliver one identical, complete copy of the genome to each daughter cell. Faults in this control can lead to cancer.

8 · Why this matters

This single molecule underpins all of genetics. Complementary base pairing explains how traits are inherited faithfully; a change in the base sequence is a mutation, the raw material of variation and evolution; and reading the code (transcription and translation) is how a gene actually builds your body. The same principles power DNA fingerprinting, genetic engineering and medicine.