Of Mice and Men
Christopher Badcock

Editors Introduction The battle between the sexes begins in the womb. Discoveries in the field of genetic conflict have revealed that in certain situations the male's genetic impulses are at odds with the female's genetic impulses. In pregnancy, the mother's interests can even be at odds with her own child's impulses. In this interview, Christopher Badcock explores and reflects on some illuminating examples of genetic conflict and its consequences.

Can you explain genetic conflict?

video oneChristopher Badcock: Genetic conflict is one of the most important discoveries in modern genetics. Basically, it is the realisation that an individual is composed of a large number of genes and that all these genes don't necessarily have the same evolutionary self-interest. They may be working against each other. Furthermore, we now know of particular genes that do exactly this.

For example, in sex determination there is a gene on the X chromosome called DAX1, which works against the Y chromosome and effectively tries to feminise somebody who would otherwise be a man. If you have only got a single copy of DAX1, which is the normal situation, you are generally male despite it. But some people because of a genetic glitch get a double copy of DAX1 on their X chromosome, and these XY males in fact mature looking like females. So you would think to look at them that they were women. In fact, genetically they are men, but they never mature as men. The reason is that the double dose of DAX1 undoes the effect of SRY, the gene on the Y chromosome that makes you male. DAX1 has been described as an anti-testis gene; in other words, it is a gene that is disputing within the individual's own genome what sex they are going to be. And we think we understand that because of the way sex determination works in mammals.

Female mammals have two X chromosomes, but male mammals have only one. That means that natural selection operates on X chromosome genes in ways to benefit females twice as often as it does in ways to benefit males, because there are always twice as many of them in females. So, what we think is happening is that there is a built-in feminist bias in the X chromosome that would ideally like everything to be female. And when an X chromosome finds itself in a male body with a Y chromosome, there's an argument. Normally it doesn't stop you from being male, but sometimes it does.

Another important insight about genetic conflict is that it goes beyond mere adaptationism. One of the problems with twentieth-century evolution theory--for which it was rightly criticised--was the tendency for evolutionists to think of good adaptations as stories, to think of a good reason why some particular trait should evolve and assume that that necessarily explained it. The trouble with such explanations is that they are quite easy to think of--and who is to know which is true? The great thing about genetic conflict is that it gives insights into things that you might not otherwise be able to explain.

One part of your work focuses on genetic conflict in newborn babies. Can you explain how this conflict between the mother and the father arises in their offspring?

video twoBadcock:
Now, this is another stunning discovery of recent genetics. Basically, there is another source of genetic conflict apart from sex chromosome conflict, and that is called genomic imprinting, discovered about 15 or 20 years ago--a big surprise. Genomic imprinting prevents certain genes from being expressed depending on which parent they came from. The classic example of this is a gene called Igf2, which stands for Insulin-like Growth Factor No. 2. It is a growth hormone.

Both the mother and the father benefit from growth in a mammal. The bigger a baby is, the better. Bigger babies have fewer infectious diseases in their lifetime, they have less proneness to cardiovascular disease, diabetes and all kinds of things. If you are a man, the taller you are, the better you do in professions, the more attractive you are to most women and so on. So, having a big baby is good news to both the mother and the father, if you are a human being. But as any woman who has ever had a baby knows, only the mother pays the cost of a large baby. She has to gestate it, provide all the resources for its development inside her, which is an enormous demand on her resources, and she has also got to give birth to the thing--which is also difficult and dangerous. So although both parents benefit from bigger babies, only the mother pays the cost.

This is why only the paternal copy of Igf2, this growth factor, is expressed, effectively saying, "Make the baby bigger!" And it does. But the mother's copy of Igf2, which you also inherit, of course, is turned off. It is imprinted but not expressed, and this is because although the mother wants the baby big, she doesn't want it that big. If it is expressed, there is a genetic glitch where both copies of Igf2 are active and you get Beckwith-Weidemann Syndrome. This is an overgrowth syndrome that causes the baby to be 50 percent bigger at birth than it should be. Such babies are normally born by cesarean delivery, and various overgrowth features include a proneness to childhood tumours, tumours and cancer being a kind of overgrowth. So Beckwith-Weidemann shows what happens if the mother does not turn her copy of Igf2 off.

Not only does the mother do that but (at least in mice) she also has another gene, Igf2r, on a different chromosome, which actively sabotages Igf2 by mopping up the growth factor. The only way you can explain this is in terms of conflict between the maternal and paternal genome over the size of the offspring; if in a mouse you knock out Igf2 and Igf2r, the mouse is the normal size. It makes no difference. If that is the case, it can only be because these genes are working against each other.

In other words, imprinted genes express conflict between mother and father over the size of the offspring: both want it as large as possible, but only the mother pays the cost, so she has an incentive to moderate a foetus's demands on her resources for its growth and development.

Can you tell us a bit more about how conflicts are played out in human pregnancy and the idea that women are actually in conflict with the child that they are giving birth to?

video three
Badcock: The symptoms of pregnancy provide many examples. One of the things that routinely happens in pregnancy is the mother's blood pressure is driven up. If you take an adaptationist view, you might think this a bad thing, since high blood pressure is often not good for the mother. But genetic conflict provides an explanation. We now know that the genes that drive up the mother's blood pressure come from the father and not from the mother. The reason we think this is happening is that high blood pressure benefits the foetus, as more blood is driven towards the placenta, resulting in a larger foetus. So it benefits the foetus for its mother to have higher blood pressure. It doesn't necessarily benefit the mother.

There is also evidence that paternal genes predominantly build the placenta, an organ designed to extract resources from the mother and one that is destructively invasive of the lining of the uterus in women, which probably explains menstruation as a preemptive defence against potential placental invasion.

We think there are similar explanations for the diabetes you can get in pregnancy. Again, we know that a paternally active gene attempts to sabotage the mother's insulin economy so the baby effectively gets more blood sugar. This again can be bad for the mother and can leave her with a lifelong predisposition to diabetes. We also think it probably explains morning sickness. Morning sickness occurs early in pregnancy, when the foetus is particularly vulnerable to poisons in the food the mother ingests which the mother but not the foetus can deal with perfectly well. We believe that the foetus is resetting the mother's vomit reflex to stop her eating things that may harm it but would not harm her. So again there is a conflict going on, over what the mother should be eating. And it's very unpleasant for the mother. But the evidence shows us that the more morning sickness a woman has, the less likely she is to miscarry.

How do you think genetics can help us explain the way the human mind and behaviour develops in terms of this male/female conflict? How can certain genes within the male help humans develop in one direction and certain genes inside the female help them to develop in the other?

video four
Badcock: In a mammal like the human being, conflict over consumption of the mother's resources is going to go on for years. There are good reasons for thinking that the kind of genetic conflicts we have been talking about in pregnancy continue after birth.

First of all, a mammal is dependent on its mother for breast milk; before the modern world of feeding bottles, formula and so on, a young mammal was literally dependent on a breast-feeding female. It couldn't survive without her. Because of the length of human childhood, children demand resources from their parents for really quite long periods, and because the mother is normally the prime caregiver and chief nurturer, there are likely to be conflicts between her genetic self-interest and the father's. All the father necessarily has to contribute to a human offspring is a single sperm, which effectively costs him nothing. It's a few minutes of quite enjoyable work.

The contribution of the mother by weight at birth is 100 billion times greater, because a newborn baby weighs 100 billion times what a single sperm weighs. That is a huge difference by any judgment. Thereafter there is a tremendous demand on the mother's resources and a very big asymmetry between the mother and the father, to the extent that any other child the mother has will always have 50 percent of her genes. That means that a human mother will always find her genes equally represented in her children. However, the genes of the father need not be in any of her other children if, for example, other men have fathered them. So, the interest of the father's genes and the interest of the mother's genes are not the same. As the mother's genes are shared equally by all the offspring, they have an incentive to cooperate with each other. If the father's genes are not shared by the other offspring, there is no incentive for them to cooperate with each other, and those genes will grab the biggest share of resources they can for themselves.

This particular genetic conflict does provide some insight into the human brain and its features. In mice--and almost certainly also in human beings--only maternal genes are expressed in building the cerebral cortex of the brain, but paternal ones alone build the limbic system. This may be explained by the fact that the limbic system controls basic instinctual and emotional needs, such as hunger and thirst, aggression, sex and other innate behaviours. A recently discovered paternally active gene, Mest, is known to control maternal behaviour in mice and men and is expressed in the limbic system.

The cerebral cortex, on the other hand, specializes in inhibiting, controlling and moderating instinctual demands from the limbic system. Interestingly, Igf2 in humans is now known to correlate with intelligence, and inhibition of irrational, instinctual responses is a key factor in intelligent behaviour. These findings suggest that the cerebral cortex may express a psychological prejudice reflecting the mother's genetic self-interest, whereas the limbic system might have a corresponding built-in bias toward the father's.

Again, the father's presence is not necessary in the way that the mother's usually is, because it is the mother, and not the father, who has to breast-feed and who would normally have been the chief caregiver during the vast majority of human evolutionary history. This may explain why the mother's genes build the part of the brain that can be nurtured and can exercise restraint, inhibition and conscience, whereas the father's genes construct the part of the brain that is notoriously incorrigible, dominated by instinct, egoism and irrationality, and is concerned with the consumption of resources and with gratification of innate needs and basic biological drives.

What do these ideas of conflict suggest for the long-running nature versus nurture debate? Can they still be seen as two opposing influences?

Badcock: Nature/nurture was one of those twentieth-century debates that generated more heat than light. With the benefit of hindsight, twentieth-century discussions of the nature/nurture issue can now be seen to have been based on a number of errors and false assumptions. Perhaps the most important was the assumption that in this controversy genes were on one side--nature--while nurture was on the other, opposed to genetics, as it were. New insights suggest that the reason the debate generated so much heat was that it was ultimately a genetic conflict. This reaches down into the very foundations of the human genome and has a genetic basis in terms of the conflict between maternal and paternal genes.

As the mother is normally the prime nurturer of the mammalian offspring, and is the environment of the baby before it is born and even after it is born, she is usually the primary agent in her offspring's environment. Because she is there to breast-feed it, look after it and so on, sometimes for many years, the mother's genes have a vested interest in nurture. She can teach you your mother tongue, as we say in English. She can rely on her physical presence and on her strategic role to program the baby with thinking and reacting and learning the kind of lessons she wants it to learn. She is in a prime position to do that.

The father does not necessarily have such an advantage. There is no real reason that the father should ever contribute more than a single sperm. Consequently, if his genes are going to have any chance of influence on the offspring they must rely on themselves as well as on gut reactions, innate responses and basic instincts. Those are fundamentally the two sides of the nature/nurture debate. One side stresses nurture--what you learned, the forces of socialisation, etc., which I think corresponds to the genetic interest of the maternal genome. The other side stresses instinct, genes and the innate gut reactions that go with what the father has to rely on in terms of this basic conflict. So it seems to me that it is a new insight into the whole nature/nurture debate, and it is really the ideological expression of a deeper genetic conflict, and one that is probably irresolvable.

Copyright The London School of Economics and Political Science.