Genes, chromosomes and genomes

From DNA to chromosomes

The DNA in one human cell is about 2 metres long but has to fit inside a nucleus about 6 micrometres across. It is packed in levels, like a thread wound onto spools, then coiled, then folded:

• The DNA double helix winds around clusters of proteins called histones, about twice round each cluster. Under an electron microscope this looks like beads on a string.
• The beaded thread coils and loops into a fibre called chromatin. Most of the time chromatin is loosely spread through the nucleus, so the genes can be read.
• Before a cell divides, the chromatin coils up much more tightly into compact, visible chromosomes. Each chromosome has been copied, so it is made of two identical sister chromatids joined at a narrow waist, the centromere.

A gene is a section of DNA that carries the instructions for one product, usually a protein. Each gene sits at a fixed position on a particular chromosome, called its locus. Genes come in different versions called alleles. For example, the gene for the ABO blood group has three common alleles. Different alleles differ by just a few bases.

Chromosome pairs and karyotypes

Body cells contain chromosomes in homologous pairs: one of each pair came from the mother's egg and one from the father's sperm. The two members of a pair are the same length, have the centromere in the same place and carry the same genes in the same order, though they may carry different alleles. A cell with two sets is diploid (written 2n). Eggs and sperm have one set and are haploid (n).

Humans have 46 chromosomes (23 pairs). Pairs 1 to 22 are autosomes, numbered roughly from largest to smallest. The 23rd pair are the sex chromosomes: females usually have two X chromosomes (XX) and males usually have one X and one much smaller Y (XY). A gene on the Y chromosome called SRY switches on development as a male about seven weeks after conception.

A karyotype is a picture of all the chromosomes in one cell, arranged in their pairs. To make one, cells (often white blood cells) are grown, stopped while dividing, burst open and stained so each chromosome shows a pattern of dark and light bands. Each chromosome has its own band pattern, size and centromere position, which is how they are matched up. Today computers do most of the sorting.

Chimpanzees have one more pair than us because, in our ancestors, two medium-sized chromosomes fused end to end to form human chromosome 2. You can still see the remains of the extra centromere and of chromosome ends (telomeres) in the middle of it.

When the number is wrong

Occasionally a pair of chromosomes fails to separate when eggs or sperm are made (1C). An egg or sperm then has an extra or a missing chromosome, and so does the baby. Most such embryos do not survive, but a few combinations do:

• Trisomy 21 (Down syndrome): three copies of chromosome 21, written 47,XX,+21 or 47,XY,+21. It occurs in about 1 in 700 to 1 in 1000 births, and the chance rises with the mother's age.
• Klinefelter syndrome (47,XXY): about 1 in 600 males. Often not noticed until adulthood, when it may cause reduced fertility.
• Turner syndrome (45,X): one X and no second sex chromosome, about 1 in 2500 females. Usually short stature and ovaries that do not develop fully.

The human genome

An organism's genome is one complete set of its DNA. The human genome is about 3.1 billion base pairs long; each body cell holds two copies, one from each parent. Typed out at one letter per millimetre, one copy would stretch about 3100 km, almost from Sydney to Perth.

The Human Genome Project, an international collaboration, set out in 1990 to read the order of all those bases. A draft was published in 2001 and a version declared complete in 2003, at a cost of about US$2.7 billion. In fact about 8% was still missing: long stretches of repeated sequence that the technology of the time could not piece together. The first truly complete, gap-free human sequence, from the Telomere-to-Telomere consortium, was published only in 2022.

The project held some surprises:

• Humans have only about 20 000 protein-coding genes, about the same as a mouse and fewer than many plants. Early guesses were 100 000.
• Only about 1–2% of the genome codes for proteins. The rest includes switches that control when genes turn on, genes for RNA molecules, repeated sequences, and the remains of ancient viruses (about 8%).
• Any two people share about 99.9% of their DNA sequence. The 0.1% that differs, about 3 million bases, accounts for much of our inherited variation.

Not all of your DNA is in the nucleus. Your mitochondria have their own small circle of DNA, 16 569 base pairs long with 37 genes. You inherit mitochondria only from your mother, through the egg. This makes mitochondrial DNA useful for tracing maternal ancestry back thousands of years.