Heredity

Mendel’s most famous experiment began with two kinds of pea plant, one that always bred purple flowers and one that always bred white. He crossed them. Every plant in the next generation had purple flowers. The white had vanished, with no pale purples in between.

Then he let those purple plants breed with one another, and the white came back. In that generation he counted 705 plants with purple flowers and 224 with white: very close to three purple for every one white. The same three-to-one ratio turned up for seed shape, for pod colour, for every trait he tested.

Something had carried the white trait, unseen, through a generation of purple plants. Mendel called the form that showed in every plant of the first cross dominant, and the form that hid, recessive.

Mendel explained his ratio with a bold guess. Each plant, he proposed, carries two hereditary “factors” for every trait, one received from each parent, and passes on just one of the two to each of its offspring. We now call these factors genes, and the different versions of one gene are called alleles. The pea’s flower-colour gene comes in a purple allele and a white allele.

When a plant has one of each, the two do not blend. One allele wins outright. An allele that shows its effect even when only one copy is present is called dominant. An allele whose effect shows only when both copies are of that kind is called recessive. In peas purple is dominant and white is recessive, so a plant with one of each has purple flowers, and looks no different from a plant with two purple alleles.

A recessive allele can travel through a family unseen. Someone who has one copy of it, paired with a dominant allele, shows no sign of it at all, because the dominant allele is masking the recessive allele. But that person can still pass the hidden allele on, and is called a carrier.

This is how a trait skips a generation. Cystic fibrosis, a serious disease that clogs the lungs with thick mucus, is caused by a recessive allele. A carrier is healthy. If two carriers have a child, though, the child may receive the recessive allele from both of them, and with two copies and no dominant allele to mask them, the disease appears. Neither parent has it, perhaps no grandparent had it, and yet it was in the family all along.

Because of dominance, you cannot always tell from looking at a plant which alleles it has. A purple-flowered pea may carry two purple alleles, or one purple and one white. Biologists therefore keep two things apart.

The pair of alleles an individual carries for a gene is its genotype. The trait that actually appears, the thing you can see or measure, is its phenotype. Two different genotypes can give the same phenotype: purple and purple gives purple flowers, and so does purple and white. Only one genotype, white and white, gives white flowers.

The distinction explains Mendel’s vanishing white. In his first cross the white allele was present in every plant’s genotype and absent from every plant’s phenotype.

Two more terms describe a genotype. If the two alleles are the same, both purple or both white, the individual is homozygous for that gene. If the two are different, one purple and one white, it is heterozygous. The words come from the Greek for “same” and “different”.

The terms matter for what a parent can pass on. A homozygous parent has only one kind of allele to give, so every one of its offspring receives the same thing. This is why Mendel’s starting plants bred true for generation after generation. A heterozygous parent gives one allele to about half of its offspring and the other allele to the rest. Every carrier of a recessive disease is heterozygous: one working allele, which keeps the carrier healthy, and one faulty allele, which may be passed on.

What will the children of two parents be like? Around 1905 the English geneticist Reginald Punnett drew a small grid to work it out, and it is still called the Punnett square. One parent’s two alleles are written across the top, the other’s down the side, and each box holds the pair a child would get from that combination.

Take two carriers of a recessive disease. Each can pass on a working allele or a faulty one, so the grid has four boxes: one with two working alleles, two with one of each, and one with two faulty alleles. Only the last gives the disease. So each child of two carriers has a 25 per cent chance of having it and a 50 per cent chance of being a carrier.

The square gives odds, not promises. The odds are the same for each child, whatever the children before it inherited.

Mendel never knew what his factors were made of or where they were kept. The answer lies in the nucleus of the cell. Genes are stretches of DNA, and the DNA is packaged into long threads called chromosomes, each carrying hundreds or thousands of genes.

Chromosomes come in matching pairs. In each pair, one chromosome came from the mother and one from the father, and the two carry the same genes in the same order, though not always the same alleles. That is why you have two alleles of nearly every gene.

The number of chromosomes is fixed for each species and says nothing about how complex it is. A human body cell has 46, in 23 pairs. Mendel’s pea has 14. A fruit fly has 8, and a dog has 78.

If an egg and a sperm each carried all 46 chromosomes, their child would have 92, and the number would double with every generation. It does not, because eggs and sperm are made by a special kind of cell division called meiosis, which halves the number. Each egg and each sperm receives 23 chromosomes: one from every pair, and so one allele of every gene.

When a sperm joins an egg, an event called fertilisation, the two half-sets combine and the full number of 46 is restored. The single cell that results is called a zygote. It is the first cell of a new person, and every cell that person will ever have is copied from it.

This is Mendel’s guess in the flesh: two copies in each parent, one passed on by each, two again in the child.

Two sisters have the same mother and the same father, and yet they are not copies of each other. The reason is that meiosis does not hand out the same half-set twice. For each of the 23 pairs, either chromosome of the pair is equally likely to go into a particular egg or sperm. Meiosis takes the parent’s alleles and shuffles them each time, and the number of possible combinations is enormous: from this choice alone, more than eight million for one mother’s eggs, and as many again for one father’s sperm.

The differences that result are called genetic variation. There is one exception. Sometimes a single fertilised egg splits in two early on, and each half grows into a baby. These are identical twins. They came from one egg and one sperm, so they have exactly the same alleles.

One of the 23 pairs of chromosomes differs between the sexes. A woman has two large chromosomes called X. A man has one X and one much smaller chromosome called Y, which carries the gene that sets development on the male path. So XX is female and XY is male.

Meiosis separates this pair like any other. Every egg therefore carries an X, because the mother has nothing else to give. A sperm carries either the father’s X or his Y, in equal numbers. If an X sperm fertilises the egg, the child is XX, a girl. If a Y sperm does, the child is XY, a boy. So the difference comes from the father’s sperm, and since half carry each, the chances at every conception are very nearly even.

About the year 1000, the surgeon al-Zahrāwī of Córdoba recorded a strange pattern in his medical encyclopedia. In one village, he wrote, men and boys bled to death from trivial wounds, and the affliction struck only the males. He could find it in none of the ancient medical books. It is among the earliest descriptions of haemophilia, a disease in which the blood fails to clot.

Some nine centuries later the pattern was explained. The gene for an essential clotting protein sits on the X chromosome, and the faulty allele is recessive. A woman who inherits it almost always has a working allele on her other X, which masks it, so she is a healthy carrier. A boy has only one X, and he gets it from his mother. If it carries the faulty allele, his Y offers no second copy to mask it, and he has the disease.

Mendel’s peas were a special case. Each of his traits was controlled by a single gene with two clear-cut alleles. Most traits are not like that. Human height does not come in “tall” and “short”. It comes in every value in between, because many genes shape it, hundreds or thousands of them, each nudging the result up or down a little. Skin colour and blood pressure are the same.

Genes are also not the whole story. Two identical twins have the same alleles for height, but if one is well fed in childhood and the other goes hungry, the well-fed twin will usually grow taller. The genes set a range, and the environment, the conditions a person lives in, decides where in the range that person ends up. Mendel’s rules still govern every one of those genes. There are simply many of them, and the world has its say too.