Steve Jones - The Language of the Genes

A small village offers little choice when it comes to picking a spouse. As a result, relatives marry and the population becomes inbred. Sometimes the married couple have each received a copy of a harmful recessive gene from their common ancestor. As a result their children are at increased risk of having two copies. George Darwin found that Oxford and Cambridge oarsmen, a healthy group, were less likely to have issued from a cousin marriage than were their more indolent peers.

There are constraints on how close a relative one may marry. Brother with sister is forbidden everywhere but even first cousin marriages may be illegal (as in most US states in the nineteenth century and in Cyprus today). This social imperative may have arisen, in part at least, from a fear that the children might be less healthy. As childhood mortality was in any case so high when the taboos were formulated (so that a small increase because of genetic disease would not be noticed) perhaps they have no biological basis at all.

The death rate does increase and development slows in the children of close relatives. Cousins share a grandparent in common. If he or she carried a harmful recessive (as almost everyone does) their children and grandchildren are more likely than average to inherit two copies. In some Japanese villages before the Second World War, up to a third of all marriages were between cousins. The huge survey of the population of Hiroshima after the atom bombs showed that the children of cousins walked and talked later than others and did worse in school. Part of this was due to the relative poverty of their parents but part reflects their heritage. The same is true in India and in Pakistan, where up to half of all marriages are still between cousins or between uncle and niece. The picture is confused here because such marriages tend to retain wealth within the family and to increase the number of children the parents can afford. Nevertheless, these too survive less well than the children of unrelated parents. First-generation Pakistani immigrants to Britain are also rather inbred. Just one birth in fifty is to such parents, but about five per cent of all inborn disease among British children is to those with Pakistani parents.

It is important not to overstate the dangers of inbreeding. Parents who are cousins have rather more than a ninety per cent chance of a perfectly normal baby, compared to more than ninety-five per cent for unrelated parents. Inbreeding has an effect, but it is dwarfed by the improvements in child health which have taken place in the past few decades. The map of human genetic diversity, based as it is on thousands of points across the genome also gives an insight into inbreeding: a child of' a marriage between a couple with a common ancestor is likely to have double copies of long sections of identical sequence. In populations known from the records to share ancestors in common, this is often the case; but, quite often, children not otherwise known to be inbred also show the same decrease in variation in parts of their genome. The effects of forgotten inbreeding long ago can, it seems, persist for many generations.

In part because of this effect, isolated populations often show high frequencies of inherited abnormalities which are rare elsewhere. Most of the gypsies of South Wales belong to one extended kindred and half their marriages are between relatives (which makes them one of the most inbred peoples on earth). One Welsh gypsy in four carries a copy of the gene for phenylketonuria, which is four hundred times more frequent in this group than in Wales as a whole. A long history of social and sexual isolation has had an effect on their genetic health. Other close-knit family groups, such as the Bedouin of Israel, Jordan and neighbouring countries, may show high levels of inbreeding with, in some places, more than half of all marriages among cousins (and a concomitant local increase in diseases such as inborn deafness). Attempts by geneticists to promote outbreeding on health grounds have had limited success.

The effects of marriages of relatives may be subtle. A few women suffer from recurrent abortion. They often become pregnant, but the foetus is lost. The problem is found among the Hutterites, a religious group who originated in the Tyrol in the sixteenth century. In the 1770s, they moved to Russia, where they flourished and multiplied ten-fold from their original community of a hundred or so. A century later, bigotry was renewed, and the Hutterites migrated to America. All thirty thousand alive today, many of whom live in South Dakota, trace their descent from fewer than ninety founders and nearly all marry within the group. Over the years they have all become quire close relatives, and the more inbred a Hutterite woman might be the longer the interval between her children. Hutterite women who find it difficult to have children share, it transpires, a high fraction of their genes with their husbands. This may reflect the malign effects of inbreeding on the embryo.

In lower animals, genetic variation on the surface of cells determines whether a sperm is allowed to fertilise a particular egg. If the two cells are too similar, then fertilisation fails. Perhaps this is why the complicated system of genetic identification on the cell surface evolved in the first place. The repeated failure of pregnancy in genetically similar husbands and wives may be a remnant of a method of ending fertilisations which arise from the attentions of too close a relative. Spontaneous abortion, perhaps in the first few weeks of pregnancy, kills them off.

Mice have the mechanism in more dramatic form. Females can tell from scent how close a relative a male might be. Given the chance, they avoid mating with their brothers. What is more, if a mouse pregnant by a relative is offered an unrelated male (or even the scent of his urine) she aborts and mates with the new partner. The genes responsible for mouse scent are linked to those that control cell-surface variation.

Among the Hutterites, too, married couples are less similar to one another for certain genes in the immune system than are pairs who are just friends. The genes involved are related to those which drive sexual choices in mice. Perhaps, quite unconsciously, most Hutterites — and most people — fall for someone with a set of identity cues different from their own. What is more, they arc keenest to avoid a partner whose genes are too much like their mother's: the Hutterite mother is to he avoided as a role model in the choice of a wife. Just how the mechanism works, no one knows, but scent may be involved somewhere.

Accidental genetic change is close to how God might play dice. Statistics is needed to study it. Population genetics is infested with mathematics, much of which is incomprehensible even to population geneticists. It is, nevertheless, unavoidable. The importance of random change depends on the size of the population. It is not enough just to know the number of people around today. What is important is its average size since it began; after all, a large town may once have had just a few ancestral inhabitants. What is more, a special kind of average is needed. This pays particular attention to episodes of reduced numbers. Like so many ideas in evolution, the idea of the "harmonic mean' comes from economics. Think of a village in ancient times, with one rich squire and many hungry peasants. Perhaps the fifty poor peasants each had an average income of a hundred pounds a year, while the squire gloried in a million. The average income was nineteen thousand pounds, which is a rather pointless statistic for anyone interested in rural reality. The harmonic mean income, in contrast, was a hundred and two pounds, which is a better reflection of what society was actually like.

The same logic applies to populations which change in number. Thus, the average size of a population whose size in succeeding generations is 1000, 1000, 10, iooo, and iooo is 802 but its harmonic mean size is only 48. Any population bottleneck — ten individuals, in this case — has a dramatic effect that can persist for many generations.