2.1 Structure of the chromosome

A chromosome is a thread-like structure in the nucleus made of one long DNA molecule wound around proteins, carrying genes in a linear order. Each species has a fixed number of chromosomes: humans have 46 (23 pairs), maize has 20, cattle 60 and the fruit fly 8. Chromosomes are visible under the light microscope only when they condense during cell division; between divisions they are spread out as chromatin. Knowing chromosome structure is the basis for karyotyping, for explaining chromosomal disorders and for understanding how DNA fits into a nucleus only a few micrometres wide. Example: a private diagnostic laboratory in Turbo prepares karyotypes from cultured white blood cells to confirm suspected cases of Down's syndrome referred by paediatricians.

Chemical composition

• DNA: About 40% of chromatin is DNA, a single double helix running the full length of the chromosome. The DNA in one human cell, if stretched out, would measure about 2 metres.
• Histone proteins: Small, positively charged proteins (H1, H2A, H2B, H3 and H4) that bind tightly to the negatively charged phosphate groups of DNA and package it.
• Non-histone proteins: Enzymes for replication and transcription, structural scaffold proteins and gene regulatory proteins.
• RNA: Small amounts of RNA being transcribed from the DNA.

Levels of packaging

1. Double helix: DNA is 2 nm wide.
2. Nucleosome: About 147 base pairs of DNA wrap nearly twice around a core of eight histone proteins (two each of H2A, H2B, H3 and H4). Nucleosomes joined by linker DNA look like "beads on a string", about 11 nm wide.
3. 30 nm fibre (solenoid): Histone H1 binds the linker DNA and pulls nucleosomes into a coiled fibre about 30 nm wide.
4. Looped domains: The fibre forms loops attached to a protein scaffold, about 300 nm wide.
5. Metaphase chromosome: Further coiling gives the fully condensed chromatid, about 700 nm wide, seen during mitosis.

Euchromatin and heterochromatin

• Euchromatin: Loosely packed chromatin that stains lightly and contains active genes being transcribed.
• Heterochromatin: Tightly packed chromatin that stains darkly, found mainly around centromeres and telomeres, and is largely inactive.
• Facultative heterochromatin: Chromatin that is condensed in some cells only, such as the inactivated X chromosome seen as a Barr body in female cells.

Parts of a metaphase chromosome

• Chromatids: The two identical halves of a replicated chromosome, called sister chromatids, each containing one DNA molecule.
• Centromere (primary constriction): The narrow region joining sister chromatids, where the kinetochore forms and spindle fibres attach during division.
• Arms: The parts on either side of the centromere: the short arm is labelled p and the long arm q.
• Telomeres: Repeated DNA sequences (TTAGGG in humans) at the tips of each chromosome that protect the ends from damage and from sticking to other chromosomes. Telomeres shorten with each division in most body cells.
• Secondary constriction and satellite: Some chromosomes have a second narrow region, the nucleolar organiser, carrying genes for ribosomal RNA; the small knob beyond it is the satellite.
• Genes and loci: Each gene occupies a fixed position, its locus, on a particular chromosome.

Classification by centromere position

Homologous chromosomes, autosomes and sex chromosomes

• Homologous chromosomes: A pair of chromosomes, one from each parent, of the same length, centromere position and gene loci, though they may carry different alleles.
• Autosomes: Chromosomes that are not involved in sex determination; humans have 22 pairs.
• Sex chromosomes: The pair that determines sex; in humans and other mammals, females are XX and males XY.
• Diploid and haploid number: Body cells carry two sets (2n = 46 in humans); gametes carry one set (n = 23).
• Karyotype: The ordered display of a cell's chromosomes arranged by size and centromere position, used to detect abnormal numbers or structure.

Prokaryotic chromosomes

Bacteria carry a single circular DNA molecule, not enclosed by a nuclear membrane, in a region called the nucleoid. It is supercoiled with the help of proteins rather than wound around true histones. Many bacteria also carry small circular plasmids, which often hold genes for antibiotic resistance and are used as vectors in genetic engineering.