The Domesticated Brain (15 page)

Epigenetics

What do the sex of a clownfish and the spread of the common cold have in common? A strange question maybe, but both are examples of epigenetic phenomena that are triggered by social behaviour. They both depend on the interaction of biology and the influence of others. Epigenetics is the study of the mechanisms of interaction between the environment and genes – the way that nature and nurture work together.

Epigenetics provides answers to the sorts of common questions we all ask ourselves. Are we born mad, bad or sad, or is our personality determined by events in our lives? Why are our children so different when we try to treat them equally? These questions are at the heart of how best to create the societies we wish to live in; often shaped and controlled by government policies and laws. The answers people prefer to give to these questions come from deep personal opinions and reflect their political persuasion about the role of the individual in society. However, epigenetics offers a new perspective to understand human development that combines our biology with our experiences.

As we noted earlier, genes are the strings of DNA molecules, found in every living cell, that instruct the cell what to become. They do this by building proteins from amino acids, which in turn are made from combinations of atoms
of carbon, hydrogen, oxygen and nitrogen. Every cell in the body has thousands of proteins and DNA determines what type a cell is and how it operates by regulating the production of proteins. Genes are like books in a library that contain information that needs to be read or transcribed in order to build the proteins. The proteins instruct the cell to become something, such as hair follicles, while others can turn them into neurons. This is a very simplistic account and there is considerably more to the story of the mechanism of genes, but for the level of discussion here, it is sufficient to know that genes are like sequences of computer code within the cell that control its operation.

Genes build humans and humans are very complex animals. Each body is made up of trillions of cells and the initial speculation was that humans must have a considerable number of genes to code for all the different arrangements of cells in our bodies. In 1990, scientists working on the human genome project began to map the entire sequence of genes for our species, using sophisticated technology that enabled computers to read off the sequences as strings of code. Very soon, it appeared that initial estimates of over 100,000 genes had been way off. Although the project is still continuing, at the last count it would appear that humans have only 20,500 different genes. That may still sound like quite a few but when you consider that the humble fruit fly,
drosophila
, has 15,000 genes, humans look decidedly puny in the genetic endowment department. In fact, much simpler living things like the banana or the rather revolting roundworm have more genes than humans and, as if that were not enough, the
organisms that have the highest and lowest numbers of genes are both sexually transmitted diseases,
trichomonas vaginalis
with 60,000 and
mycoplasma genitalium
with 517.

So the number of genes does not reflect the complexity of the animal. The reason we initially overestimated the number of genes for humans was because the role of epigenetics was not yet fully appreciated. Moreover, it turns out that there is more information encoded in the few genes we have than is ever actually used. Only 2 per cent of genes appear to be related to building proteins. This information is only activated when the gene becomes expressed and geneticists now understand that only a fraction of genes are expressed. In fact, gene expression is the exception and not the rule. The reason is that genes are sets of IF–THEN instructions that are activated by experiences. These experiences operate through a number of mechanisms, but genetic methylation is typically one that silences a gene and is believed to play a major role in long-term changes that shape our development. If you think about genes like books in a library and the library is the full genome, then each gene can be read to build proteins. Methylation acts a bit like moving a book out of reach so the information to build proteins cannot be read, or blocking access to it by placing some furniture in front of the book.

DNA may instruct cells how to form and organize themselves to build our bodies but these instructions unfold within environments that modulate their instructions. For example, the African butterfly
bicyclus anyana
comes in two different varieties, either colourful or drab, depending on whether the larvae hatch in the wet or the dry season. The
genes do not know in advance, so are simply switched on by the environment.

Sometimes those switches are social in nature. For many fish, the social environment can play a fundamental role in shaping how genes operate, even to the extent of switching sex. Clownfish live in social groups that are headed up by the top female. What Pixar’s film
Finding Nemo
did not tell the audience is that clownfish have the potential for transsexuality. When the dominant female in a school of clownfish dies, the most dominant male changes into a female and takes over. Or consider the humble grasshopper. When the population of grasshoppers becomes overcrowded, they change colour, increase in size and become gregarious and socially sensitive to other locusts. This transformation from a solitary grasshopper within a swarm is triggered simply by the amount of physical contact they have with others.
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Social environments can trigger a metamorphosis in a number of different species, but is there any evidence that social environments regulate human genes in a similar way? The example of the common cold helps to address the question. Social environments increase our susceptibility to the common cold but also influence how we fight it. Colds are more common in the winter months, not because of the lower temperatures (contrary to popular belief) but through the transmission of the virus between people. One reason why the virus may be more prevalent in the winter months is that we tend to congregate closer as the nights draw in, enabling the virus to transmit more readily from one to another. Viruses are small packets of DNA made up of about 10–100
genes that enter our cells and hijack the protein production to make copies of themselves. As this infection multiplies, the normal function of the cells and ultimately the whole of the body comes under attack. However, a virus’s ability to express and duplicate its own DNA is regulated by our own body’s reaction to social stress.

Social stress and isolation have long been known to affect viral infections, which is why we can all do with a little TLC along with our chicken soup when it comes to nursing a cold.
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All this sounds like common sense, but what this folk wisdom reflects is an increasing understanding of the role of social factors in illness. An analysis of the DNA in the white blood cells or
leukocytes
of lonely adults revealed different levels of gene expression in comparison to adults who were not lonely.
⁴²
Specifically, the genes responsible for producing antibodies to infection were downgraded, making their immune response less effective. This may explain why lonely adults are more vulnerable to diseases. What is remarkable is that the different gene expression is only found in those individuals who feel they are lonely and is not related to the actual number of social contacts they have. Even some of the most popular people can still be the loneliest in a crowd because it is how they feel that is more important, rather than the extent of their actual social circles.

If social factors can regulate the expression of viral genes, then our own complement of roughly 20,000 genes is likely to be regulated in biologically significant ways by social factors as well.
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It is not only our biology but also our psychology that affects how we cope with illness.

Lamarck’s daft idea

What is the evidence for epigenetic processes in humans? After all, humans do not spontaneously change sex when a dominant female leaves the group, but critical events can trigger changes in how our genes operate and sometimes the resulting changes in behaviour can be passed on to subsequent offspring. This is an astonishing idea but is not new. In the early nineteenth century a minor French noble, Jean-Baptiste Lamarck, proposed that characteristics acquired during a lifetime could be passed on to the next generation.

In support of this idea, he showed that the sons of blacksmiths had larger arm muscles than the sons of weavers before they ever took part in the family business, which he interpreted as an inherited characteristic. As another example, he suggested that giraffes’ necks became long through their constant reaching up to high branches to eat leaves – a physical trait that they then passed on to their young.

Contrast this Lamarckian notion to Darwinian natural selection. In Darwin’s theory there are two mechanisms that lead to change. The first is spontaneous mutation that generates variations among members of the group. Today, we now understand that this variation arises from genetic processes. Second, the environment operates to select those variations that endow the individual with a competitive advantage to breed and pass on the variation. With successive generations, the variant becomes stable in the population. In the case of giraffes, those born with a mutation that resulted
in them having longer necks were more successful in breeding. It was not the experience of trying to reach leaves that was passed on to the offspring, but rather the genes that increased the length of the neck.

Darwin originally suggested that long necks would provide an advantage for reaching more leaves, but it turns out that there are a number of competing explanations.
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What is known is that the mechanism of inheritance is not Lamarckian. Rather, long necks originated as a genetic mutation that was passed on while giraffes with short necks did not get the same opportunity to reproduce for some reason. Lamarckian theory has been roundly denounced as daft in scientific circles but epigenetics is casting new light on his ideas. Maybe experiences during a lifetime can influence the biology of the next generation.

There are so many problems and errors with Lamarck’s evidence that it would be all too easy to consign the notion to the dung heap of bad ideas. Moreover, Darwin’s theory of evolution by natural selection is simply better at explaining and predicting the data. And yet aspects of Lamarck’s daft idea have been resurrected with the rise of epigenetics. Sometimes events during one’s lifetime can affect the next generation. Epigenetics explains how environmental signals change the activity of genes without altering the underlying sequence of the DNA. The process of natural selection will ultimately correct any epigenetic influences of the environment. Rather, the effects are more to do with the switches that are being flipped by epigenetic processes. So Lamarck may have gained a minor battle, but Darwin has won the war
in explaining how we pass on characteristics from one generation to the next. Epigenetics may even explain why humans traumatized as infants grow up with an emotional legacy that can stay with them for the rest of their lives. Once again, studies of the rearing practices of generations of laboratory rats have shown how early experiences shape the bond between mother and daughters.

Licking rats

What could be worse than licking a rat? For many people, rats are disgusting abhorrent pests associated with poverty, disease and death. This is rather unfair, as the female rat is an intelligent and social animal with a strong maternal instinct. When she is rearing her pups in the nest, the female rat will invest time licking and grooming her brood like an attentive mother. Some mother rats are much more conscientious, with very high rates of licking, whereas others are less so – a trait these mothers share with all their sisters.
⁴⁵

What is remarkable is that if you take female pups from a low-licking mother and have them raised in the litter of a high-licking mother, they will acquire this attentive trait. Likewise, if you cross-foster in the opposite direction, you get the opposite effect.
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Is this rat example simply a case of learning how to raise your pups? There is more to it than that. Grooming and licking appears to regulate the baby rat’s response to stress. Those mothers with a high licking rate produce offspring who cope much better with stress than those from a low-licking mother. They also grow up into
more resilient adult rats and, if female, pass this behavioural trait on to the next generation.
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They are better adapted to reproduce.

You can even generate this effect if rat pups are reared by humans and given different levels of handling during the early days. This activity changes the baby rats’ HPA response by altering their reactivity to stress. The grooming and licking releases the ‘feel-good’ neurotransmitter serotonin that regulates the gene that controls for GR in the hippocampus. In contrast, this gene is switched off in the under-stimulated pups, whereas it is almost never methylated in the pups of high-licking grooming mothers. With higher levels of GR expressed in the hippocampus, the rat is better able to regulate the HPA effectively. Even though DNA methylation patterns tend to be stable, if you cross-foster the pups of high-and low-licking mothers during the critical period, you can reverse the methylation of the gene in the hippocampus. In short, the early grooming experience is turning the genes on or off.
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This may be all well and good for rats, but what of humans? Is there any evidence of biological embedding of early experiences later in life? Post-mortem examination of suicide victims revealed that GR expression in the hippocampus was reduced in those with a history of early abuse compared to those without this childhood trauma.
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What makes this finding all the more incredible is that it was not the stress of events that ultimately led them to take their own lives that produced this genetic difference, but rather events during their childhood that were responsible for silencing the genes.