What is a gene?

A gene is neither a unit of life like a cell nor a particle of matter like an atom. The closest thing is information: a piece of text.

Inside our cells is a very long, thin molecule called DNA. Along it run four kinds of “letter”, A, T, G and C, and their order carries information. A gene is one stretch of that long string of letters that spells out how to make one of the body's parts.

Where are genes, and what form do they take? Let's zoom in, starting from the whole body.

The human body is made of about 37 trillion cells. In the middle of most of them is a small sac called the nucleus, and that is where DNA is kept.

The amazing part is the length. Stretch out the DNA in a single cell and it comes to about two metres, packed into a nucleus less than a hundredth of a millimetre across. The trick is spooling: DNA wraps around proteins called histones, which are folded again and again into a compact bundle.

Zoom in further and DNA turns out to be two strands twisted into a double helix, built from perfectly ordinary atoms: carbon, hydrogen, oxygen, nitrogen and phosphorus. So, seen as a thing, a gene is part of a molecule of neatly joined atoms. But its value lies not in the atoms but in the order of A, T, G and C.

“Is a gene more like a cell, or an atom?” Here is the answer as a table.

So how are genes laid out along the string of DNA letters? A tiny piece, magnified, looks something like this.

Using the book analogy, the pieces fit together like this:

• Genome — all of one person's information: a collected works of about 3 billion letters
• Chromosome — a volume of that collection. Humans have 23 volumes, one set from each parent, 46 books in all
• Gene — one recipe. About 20,000 are recipes for proteins
• Codon — a three-letter “word”; each word stands for one amino acid
• Base — the four “letters”, A, T, G and C

In fact, the parts read as protein recipes make up only about 1.5% of the genome. The rest includes gene switches (which decide when and how much a gene is used), recipes for another kind of molecule called RNA, and stretches whose roles are still not well understood.

The history of their discovery shows clearly that genes are information. Long before anyone saw them, genes were proposed as units that could not be seen but had to exist.

In Mendel's day, the gene was a theoretical entity. It took about 90 years to learn that it is a sequence of letters written on a molecule called DNA.

A gene does nothing just by being written down. It only goes to work when it is read and turned into a protein, a process shared by almost all living things.

1. Transcription — inside the nucleus, just the needed gene is copied into a molecule called mRNA. The precious original (DNA) stays in the nucleus; only the copy goes out
2. Translation — outside the nucleus, a “factory” called the ribosome reads the mRNA three letters at a time, linking the matching amino acids one by one
3. Folding — the chain of amino acids folds into a particular shape, and the protein is complete

Four letters in groups of three give 64 combinations, enough to specify 20 amino acids plus a “stop” signal. The proteins made this way are the body's real workers.

Genes are just strings of letters. Why do they have so much influence over living things? There are four main reasons.

1. Every cell carries the same collection

We each start as a single fertilised egg. Every time it divides, DNA unzips its two strands and uses each as a template for an exact copy (A pairs with T and G with C, so one strand is enough to rebuild the other). That is how almost all of our 37 trillion cells end up with their own copy of the same collection.

2. They are the recipes for the body's tools

As we saw, proteins do the actual work: building materials, chemical reactions, signals, defence. All of their recipes are written in genes, so a change in a gene can ripple out to any part of the body.

3. Switches decide which pages are open

A nerve cell and a muscle cell carry the same collection; the difference is which pages are open. Cells switch genes on and off, using only the ones they need. That is how one set of plans produces cells with completely different shapes and jobs.

4. They pass from parents to children

We have two copies of most genes, one from our father and one from our mother. More than 99% of the letters are the same from person to person; the tiny remainder shapes our individual looks and constitution. Sometimes a single letter changes a protein's shape enough to cause disease (sickle cell disease is one example).

This is probably the question that matters most. The answer: some things genes decide, and some things genes alone cannot.

Birth: a program for building a body from one cell

The order in which the fertilised egg divides, which part becomes the head and which the hands: these building steps follow a program written in our genes. Remarkably, the program even includes steps where cells deliberately die. A baby's hands start out webbed in the womb, and the five fingers separate when the cells between them die on schedule. The discovery of how this “programmed cell death” works won the 2002 Nobel Prize in Physiology or Medicine. Even in adults, more than a trillion cells are replaced this way every day.

Ageing: a limited ticket, and slowly mounting damage

Each end of a chromosome has a protective cap called a telomere, which gets a little shorter every time the cell divides. It works like a ticket with a fixed number of rides: even cells from a foetus stop multiplying after about 50 divisions and become “senescent” cells. DNA is also damaged almost daily by ultraviolet light, radiation and reactive oxygen, and the damage that is never repaired piles up with age.

So is lifespan itself inherited? A 2018 study of family trees covering more than 400 million people estimated that genes explain less than 10% of the differences in lifespan (7% or less). Families that seem long-lived often simply share similar lifestyles and surroundings.

Illness: diseases that are nearly certain, and diseases where genes shift the odds

The links between genes and disease fall into two broad groups:

• Diseases almost entirely decided by one gene — Huntington's disease, for example, is caused when a three-letter repeat, “CAG”, inside the HTT gene becomes too long. With 40 or more repeats the disease almost always develops, usually showing in a person's thirties or forties. Inheriting a single altered copy from one parent is enough
• Diseases where many genes and the environment intertwine — most common conditions, such as type 2 diabetes and high blood pressure. Hundreds of gene variants, each with a small effect, add up to shift a person's risk, and diet, exercise and sleep do the rest

Cancer is a genetic disease too, but most cancers are not inherited. They arise when damage builds up in the DNA of body cells over a lifetime and breaks the brakes on cell growth. Changes like these in body cells are not passed on to children.

Death: cell death is programmed, a human lifespan is not scripted

At the level of cells, death really is part of the genetic program. But there is no “death gene” that sets the age at which a person dies. Ageing involves many genes, including those for telomeres, DNA damage and the body's repair capacity, along with the environment and plain chance.