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Everyone knows that you get genes from both parents and that this is just as well because if one copy is faulty you can often get by with the other. Indeed, the whole point of sexual reproduction seems to be to create offspring who benefit from the genes of two parents, rather than simply relying on one, as happens in asexual, clonal reproduction.
But true as this may be, we now know that some important genes are exceptions, and although they are inherited from both parents in the normal way, they are only expressed from one copy. These imprinted genes are paradoxical for this reason, and prime candidates for causing problems if they are faulty, thanks to lacking a backup. According to the imprinted brain theory, they (and other genes that can act in a similar way) are the cause of mental illnesses that have a genetic origin. Indeed, the theory implies that if you could explain imprinting you could also explain, not just the how? of mental illness, but also the why?
Imprinting makes evolutionary sense in terms of what you might call the Mother’s Baby—Father’s? Maybe! Principle. Because fertilization takes place internally in mammals, paternity is never as certain as maternity is: hence the question and exclamation marks. Mammalian mothers provide 100% of nurture during gestation and lactation, and usually the vast majority of it throughout their offspring’s development. The mammalian father’s sole obligatory contribution, by contrast, is a single sperm. And because lifetime monogamy is very rare in mammals, there is no necessary reason why any other of a female’s offspring should share the same father in the way in which they do the same mother.
This extreme asymmetry in parental care and investment means that, from the point of view of paternal genes in an offspring, pregnancy, lactation, and all later maternal nurture represent a free lunch for which the father need make no obligatory payment whatsoever but from which his offspring benefits. For the mother, on the other hand, all this represents a huge cost that any woman who has been through pregnancy and childbirth will appreciate only too well.
This appears to explain imprinting in genes such as IGF2, which is maternally imprinted and only expressed from the father’s copy. IGF2 stands for insulin-like growth factor 2 and is a growth hormone, encouraging the offspring to consume maternal resources to the advantage of its—and its father’s genes invested in it. In a previous post, I pointed out that every hormone needs receptors, and in mice a paternally imprinted gene, Igf2r (for Igf2 receptor) builds a type of receptor for IGF2 that mops it up, producing no growth effects (the type 2 receptor in the diagram below). Effectively, maternally expressed Igf2r contradicts and sabotages paternally expressed Igf2, as the diagram illustrates.
Cases such as this suggest that there ought to be about as many maternally as paternally imprinted genes, but now a new study of mouse genetics shows a surprising bias in favour of paternal expression. The study identified 95 murine genes with significant evidence of imprinting and concluded that even though classical imprinting is under genetic control, it is incomplete and reveals a global imbalance favouring paternal genes. Imprinted genes were 1.5 times more likely to be expressed from the paternal as compared to the maternal copy. However, there are variations in different organs, with paternal gene expression predominating in the brain but maternal expression predominating in the placenta.
At first sight, this might seem to be the opposite of what you might expect, given that the placenta is an organ designed to extract resources from the mother during gestation. But as the case of Igf2r shows, maternal genes can fight back, and appear to have established precedence in the placenta—at least in mice. So what of the brain, and why should paternal genes predominate there?
The illustration below represents one of the first and most astonishing findings on which the imprinted brain theory was built. This was that in mice paternal genes are mainly expressed in the black areas—the hypothalamus and other parts of the so-called limbic brain—whereas maternal genes are predominantly expressed in the striatum and cortex, as indicated by the dark grey, especially in frontal areas. Elsewhere in the mouse brain, as you would expect, genes from both parents are expressed equally (light grey shading). Again, a later study of gene expression in the brains of mice found that 40–50% more neurons expressed the mother’s X chromosome as compared with the father’s in the prefrontal and other parts of the cortex. By contrast, there was no difference in X chromosome expression in the hypothalamus. It also reported more maternal contribution during development, but more paternal gene expression in adulthood.
The cortex is vastly bigger in humans relative to the limbic brain, and this suggests that it is not simply the number of parental genes that are expressed that matters, but where and how they are expressed. Furthermore, although we can’t extrapolate directly from mouse to man, it remains a fact that the mouse genome closely resembles the human one, being about the same size, and having murine equivalents for nearly all human genes. And where differential expression of imprinted genes is concerned, one study showed that in 65 families, abilities mediated by frontal cortical lobes closely correlated between children and mothers rather than fathers. Again, the prefrontal cortex tends to be larger in women, while elements of the limbic system such as the amygdala and hippocampus tend to be larger in men. Indeed, they are larger still in autism but smaller in schizophrenia—just as the imprinted brain theory’s attribution of autism to paternal and psychosis to maternal gene expression implies.
Finally, if there is indeed a bias in favour of paternal genes expressed in the brain, there could be a very good reason why. Brains (and therefore behaviour) can be influenced from two different directions: from the bottom up through gene expression, or from the top down in terms of inputs from the environment via the senses, and both can be very influential. Thanks to her pre-eminent social role as the prime carer and pervading environmental influence on her children, the mammalian mother is much better placed to exploit top down influence—nurture, in other words—than is the father. Not only can the mother's genes build her child's brain from the bottom up, but she can also exploit her top down social role to program that brain in all kinds of ways that can benefit her, for example in teaching a child its "mother tongue," and then using it for instruction, command, and control of her offspring. The very different evolutionary predicament of the mammalian father, on the other hand, is likely to force him to rely more on the bottom up influence of his genes: nature, not nurture, if you like. Certainly, making due allowances for the simpler situation in mice, this could explain both the paternal bias of gene expression in the murine brain and its postponement until the mother's period of influence is over—not to mention why the father's genes are so strongly expressed in limbic brain centres concerned with energy-consuming issues such as hunger, thirst, and heat-regulation.
And more to the point where the imprinted brain theory is concerned, it could of course suggest a similar situation in the human case. Indeed, as I concluded in Evolutionary Psychology as long ago as the turn of the century, this could be the evolutionary basis of the bitter nature/nurture controversy—particularly as it applies to the most controversial issue of all: the genetics of behaviour, personality, and the mind.
(With thanks to Louis Badcock and the Wellcome Library, London.)
