Patterns of inheritance in humans can, then, follow the same rules as those found in peas. However, biology is rarely pure and never simple. Much of the history of human genetics has been a tale of exceptions to Mendel’s laws.
For example, variants do not have to be dominant or recessive. In some blood groups, both show their effects. Someone with a factor for group A and group B has AB blood, which shares the properties of both. At the DNA level, the whole concept of dominance or recessivity goes away. A change in the order of bases can be identified with no difficulty, whether one or two copies are present. Molecular biology makes it possible to see genes directly, rather than having to infer what is going on, as Mendel did, from looking at what they make.
Another result which would have surprised Mendel is that one gene may control many characters. Thus, sickle-cell haemoglobin has all kinds of side-effects. People with two copies may suffer from brain damage, heart failure and skeletal abnormalities (all of which arise from anaemia and from the blockage of blood vessels). In contrast, some characters (such as height or weight) are controlled by many genes. What is more, Mendelian ratios sometimes change because one or other type is lethal, or bears some advantage.
All this (and much more) means that the study of inheritance has become more complicated in the past century and a half. Nevertheless, Mendel’s laws apply to humans as much as to any other creature.
They are beguilingly simple and have been invoked to explain all conceivable – and some inconceivable – patterns of resemblance. In the early days, long pedigrees claimed to show that outbursts of bad temper were due to a dominant gene and that there were genes for going to sea or for ‘drapetomania’ – pathological running away among slaves. This urge for simple explanations persists today, but mainly among non-scientists. Geneticists have had their fingers burned by simplicity too often to believe that Mendelism explains everything.
Mendel had no interest in what his inherited particles were made of or where they might be found. Others began to wonder what they were. In 1909 the American geneticist Thomas Hunt Morgan, looking for a candidate for breeding experiments hit upon the fruit fly. It was an inspired choice and his work, with Drosophila melanogaster (the black-bellied dew lover, to translate its name) was the first step towards making the human gene map.
Many fruit fly traits were inherited in a simple Mendelian way, but some showed odd patterns of inheritance. When peas were crossed it made no difference which parent carried green or yellow seeds. The results were the same whether the male was green and the female yellow, or vice versa. Some traits in flies gave a different result. For certain genes – such as that controlling the colour of the eye, which may be red or white – it mattered whether the mother or the father had white eyes. When white-eyed fathers were crossed with red-eyed mothers all the offspring had red eyes but when the cross was the other way round (with white-eyed mothers and red-eyed fathers) the result was different. All the sons had white eyes and the daughters red. To Morgan’s surprise, the sex of the parent that bore a certain variant had an effect on the appearance of the offspring.
Morgan knew that male and female fruit flies differ in another way. Chromosomes are paired bodies in the cell which appear as dark strands. Most of the chromosomes of the two sexes look similar but one pair – the sex chromosomes – are different. Females have two large X chromosomes; males a single X and a much smaller Y.
Morgan noticed that the pattern of inheritance of eye colour followed that of the X chromosome. Males, with just a single copy of the X (which comes from their mother, the father providing the Y) always looked like their mother. In females, the copy of the X chromosome from the mother was accompanied by a matching X from the father. In a cross between white-eyed mothers and red-eyed fathers, the female offspring have one X chromosome bearing ‘white’ and another bearing ‘red’. Just as Mendel would have expected, they have eyes like only one of the parents, in this case the one with red eyes.
The eye colour gene and the X chromosome hence show the same pattern of inheritance. Morgan suggested that this meant that the gene for eye colour was actually on the X chromosome. He called this pattern ‘sex-linkage’. Chromosomes were already candidates as the bearers of genes as, like Mendel’s hypothetical particles, their number is halved in sperm and egg compared to body cells.
Everyone has forty-six chromosomes in each body cell. Twenty-two of these are paired, but the sex chromosomes, X and Y, are distinct. Because the Y carries few genes, in males the ordinary rules of Mendelian dominance and recessivity do not apply. Any gene on the single X will show its effects in a male, whether or not it is recessive in females.
The inheritance of human colour blindness is just like that of Drosophila eye colour. When a colour-blind man marries a normal woman none of his children is affected, but a colour-blind woman whose husband has normal vision passes on the condition to all her sons but none of her daughters. Because all males with the abnormal X show its effects (while in most females the gene is hidden by one for normal vision) the trait is commoner in boys than in girls. Many other abnormalities show the same pattern.
Sex-linkage leads to interesting differences between the sexes. For the X chromosome, females carry two copies of each gene, but males only one. As a result, women contain more genetic information than do men. Because of the two different sensors for the perception of red controlled by a gene on the X chromosome, many women must carry both red receptors, each sensitive to a slightly different point in the spectrum. Males are limited to just one. As a result, some women have a wider range of sensual experience for colour at least – than is available to any man.
Whatever the merits of seeing the world in a different way, women have a potential problem with sex-linkage. Any excess of a chromosome as large as the X is normally fatal. How do females cope with two, when just one contains all the information needed to make a normal human being (or a male)? The answer is unexpected. In almost every cell in a woman’s body one or other of her two X chromosomes is switched off.
Tortoiseshell cats have a mottled appearance, which comes from small groups of yellow and black hairs mixed together. All tortoiseshells are females and are the offspring of a cross in which one parent passes on a gene for black and the other transmits one for yellow hair. Because the coat-colour gene is sex-linked about half the skin cells of the kitten switch off the X carrying the black variant and the remainder that for yellow. The coat is a mix of the two types of hair, the size of the patches varying from cat to cat.
The same happens in humans. If a woman has a colour-blind son, she must herself have one normal and one abnormal colour receptor. When a tiny beam of red or green light is scanned across her retina her ability to tell the colour of the light changes as it passes from one group of cells to the next. About half the time, she makes a perfect match but for the rest she is no better at telling red and green apart than is her colour-blind son. Different X chromosomes have been switched off in each colour-sensitive cell, either the normal one or that bearing the instruction for colour blindness.
The inheritance of mitochondrial genes also shows sexual differences. When an egg is fertilised, much of its contents, including those crucial structures, is passed on to the developing embryo. Mitochondria have a pattern of inheritance quite different from those in the nucleus. They do not bother with sex, but instead are passed down the female line. Sperm are busy little things, with a long journey to make, and are powered by many mitochondria. On fertilisation these are degraded, so that only the mother’s genes are passed on. In the body, too, mitochondria are transmitted quite passively, each cell dividing its population among its descendants. Their DNA contains the history of the world’s women, with almost no male interference. Queen Elizabeth the Second’s mitochondrial DNA descends, not from Queen Victoria (her ancestor through the male line) but from Victoria’s less eminent contemporary Anne Caroline, who died in 1881.
Mitochondria, small as they are, are the site of an impressive variety of diseases. Their sixteen and a half thousand DNA bases – less than a