Sunday, October 27, 2013

The genes that make you a true individual

Your compatibility genes make you unique as well as affecting all parts of your life, from your health to your choice in partner, finds Mark Viney

I AM me, and thou art thee. We are all individuals, and our individuality matters.

During the second world war, doctors tried to save severely burned pilots with grafts of donated skin. The grafted skin looked good for a few days, but then withered and died. Studies led by Peter Medawar – who won a 1960 Nobel prize for his work – found that grafts of an individual's own skin did work, while those of a donor did not.

We now know that the donor skin grafts failed because the recipient's immune system recognised the grafted skin as foreign and killed it. The same process leads to the rejection of donated organs. But how does our immune system learn what is self and what is foreign?

As immunologist Daniel Davis explains in The Compatibility Gene, it is all down to specific genes – formally known as the major histocompatibility complex genes.

Although our appearance, lifestyle and career path may make us feel unique, we are actually always one of a group: it is only our compatibility genes that define us as true individuals. Davis provides a well-written and easy-to-read account of the sometimes complicated biology behind the crucial genes that affect our lives so profoundly.

From early on in the evolution of life, individual cells – and later multicellular organisms – developed the ability to recognise that which was the same as them, and that which was different.

Davis recounts how, when we are growing as fetuses, our compatibility genes train the immune system to recognise our own cells and tissues as "self" and so, in healthy people, they know what not to attack. Our cells are identified by the presence of unique surface molecules, coded for by the compatibility genes.

Meanwhile, our immune systems make antibodies. These are randomly generated in a kind of lottery, which means they will be able to attack a great diversity of molecules, especially those of pathogens.

By chance, though, a few of these antibodies will also match the compatibility-gene molecules on our own cells. Leaving such antibodies around would be suicide – literally. To stop this, Darwinian-style selection comes into play within the immune system, eliminating any cells that produce antibodies matching "self".

In this way, all of our cells are defined by compatibility genes, and our immune systems have been trained to recognise them as self, so that everything else is foreign and, thus, is attacked. All life on the planet – single-celled bacteria, plants and animals – consists of individuals differentiated by a compatibility gene system.

The pilots' skin grafts failed, therefore, because a successful transplant of any tissue requires matching of donor and recipient compatibility genes. This is not an easy task, as Davis makes clear by a bit of self-study.

He recounts how he gained a measure of his individuality by having his compatibility genes analysed by an organ donation matching service, which immunologically mapped key parts of these genes. Out of 18 million people in an international database of potential organ donors, he is just one of four similar, but not identical, individuals. His wife comes in at one of 185 out of the 18 million – as he says, "not quite the one in a million I always thought she was".

But compatibility genes affect many more aspects of our lives than just organ donation, says Davis. They are at work all the time, but their industry is largely silent to us.

Double-edged diversity

Think back to your last winter cold. When you caught it, viruses entered your cells and started to grow. These infected cells signalled the disease to your immune system by putting small pieces of virus on their own surface, attached to one of your compatibility gene products. As Davis explains, "a cell constantly 'reports' on its surface samples of all the proteins that it is making", and the immune system goes looking for anything that is "non-self". In this way, during that cold your immune system recognised the "infection flag" on those virus-infected cells, killed them, and killed the viruses too.

The sort of compatibility genes you are endowed with has a huge effect on the immune response you made to that infection, and so how ill you got. They define your disease susceptibility, or resistance. You are an individual and your immune response to an infection is individual too.

It is also possible to trace human history in the diversity of compatibility genes. Our African ancestral home has the greatest diversity of compatibility genes on the planet. In Africa, there is a correlation between compatibility gene types and language groups, reflecting how migration and interbreeding have simultaneously affected genetics and linguistics. Humans moved out of Africa, founding new populations from small groups of individuals. The further we are from Africa then, roughly, the less diverse our compatibility genes are because smaller groups of people – and fewer compatibility genes – founded more distant populations.

In the modern world, people are more mobile than ever, and many have moved away from their ancestral homes. As a result, most urban Western societies have planet-wide mixtures of compatibility genes, geographically rearranging our diversity. Although there may be a long-term effect on genetic diversity in these areas, it depends on who has a family with whom. But with this modern global shake-up, we have to take note of our compatibility genes – take note of our individuality.

Different compatibility genes cause different responses to vaccination, different disease susceptibility, and different responses to treatment, so recognising compatibility genes will ultimately give better health for all. Such an approach is not politically neutral, with its echoes of racism and segregation, but our compatibility gene individuality cannot be ignored. Although Davis gives an up-to-date account of the science, he steers clear of the wider societal implications that might lie ahead.

Where else might compatibility gene effects be felt? Possibly in that most individual of decisions – the choice of a mate. Davis recounts the flurry of studies, starting in the 1990s, that wondered whether human attractiveness – based on smell – was controlled by compatibility genes. Researchers asked women to rate how attractive they found the odour of T-shirts worn previously – and sweated in – by men. They then looked at whether there was a correlation in women's responses and the relatedness of compatibility genes between the individual men and women.

The result from the first study was that women preferred the smell of men with compatibility genes dissimilar from their own. This answer was controversial; study and counter-study have followed since, with some finding these effects, others not.

Davis covers human compatibility genes well but a larger nod to compatibility systems in other animals and plants would not have gone amiss. These ubiquitous codes for uniqueness are a good reminder that we are just another species of animal. It is clear that other animals' compatibility genes are involved in their choice of mate, perhaps to avoid inbreeding.

Humans are so closely related to all other mammals – different physical appearances belying the very close physiological similarity – that analogous effects must occur among us. Indeed, it would be startling if we didn't use compatibility genes in some way when choosing our mates. Think of that next time you get intimate with the love of your life.

Viney, Mark. 2013. “The genes that make you a true individual”. New Scientist. Posted: September 17, 2013. Available online:

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