The arrival of a child leads doting parents to search for likenesses in their offspring. Eye colour, shape of the chin, cheeks or ear lobes, all are ripe for discussion about the influence of the child's forebears. Yet the most obvious impact of heredity is often on skin and hair; as most people know, the genetic imprint on our largest organ - the skin - is large.
For a child's red hair is not explained by the foods, vitamins or lifestyle of a pregnant mother, but by a good old return to biological reductionism. Genes are at work, and we need to understand their Mendelian inheritance or, perhaps more likely, in Sam Shuster's memorable words, their "role in the genetic haystack of life".
Ironically, despite the standard introduction to genetics in school textbooks, we have only recently gained insights into the genes underpinning those most diverse of human characteristics: skin and hair colour.
How we got there makes a good story for those who don't believe in the fairly tale of managed discovery and foresight exercises. Advance has relied on two disparate activities, by different sorts of people doing different sorts of science: the study of mice, and the study of bacteria and viruses. And continued advance will rely on remembering something increasingly overlooked - the study of humans.
The 'mouse fancy' started in China several centuries ago as a simple collectors club for mice with strange or unusual coat colours. Such mice, often the ones we are now more familiar with such as those with pink eyes and white coats (albino mice), were the subject of much curiosity.
Several centuries on, people cross bred many of these strains – and, because merely looking at the coat was easy (and non-invasive), seized on using coat colour as a tool to understand how genes behaved. If you cross black mice and white mice, why do you not get grey mice?
While mouse breeding could help show principles of inheritance, the study of simpler life forms such as bacteria and viruses allowed the development of techniques that have allowed us to identify and characterise genes at the molecular level: the technological revolution that has dominated biology for the last two decades.
Of course mice are not men, but there are many analogies that can be made between the control of pigment in mice and men. The study of red hair and sun-sensitive skin (skin that burns rather than tans in response to sunshine) is one such example.
In the skin
There are two sorts of pigment in skin or hair: eumelanin, which is brown or black, and phaeomelanin, which is red or yellow. Mice with yellow hair had long been of interest to mouse geneticists and in the early 1990s Roger Cone in Oregon cloned the gene underpinning this characteristic: the melanocortin 1 receptor (MC1R). In his original paper Cone presciently suggested that this gene might be important for human pigmentation.
Seizing on this observation, my laboratory and those of colleagues Tony Thody and Ian Jackson showed that people with red hair do indeed have variants of this gene. Most red-heads carry two changes, one on the chromosome from their mother and one on the chromosome from their father. We went on to show that people who carry only one different allele tend to burn easily in the sun (even though they didn't have red hair), and are more likely to have a large number of freckles.
The MC1R gene encodes a receptor that is expressed on melanocytes (pigment cells in the skin) and responds to a hormone that stimulates the production of the dark pigment eumelanin. So this makes perfect sense: if you have a variant in the MC1R gene that inactivates the receptor, eumelanin will not be made, phaeomelanin will accumulate in the pigment cells, and you will have red hair and fair skin
Why is this of interest? A number of reasons – not just from the point of view of health, but also to do with simple curiosity.
First, how easily you burn and how poorly you tan is a major risk factor for most forms of skin cancer. If you have dark skin, you are perhaps a hundred times less likely to get melanoma or a range of other tumours. Melanin is a very effective sunblock.
Despite the above, there has a been a resurgence of interest in using ultraviolet radiation (the part of sunshine that causes the burning) to treat patients with a range of skin diseases such as psoriasis and eczema. It may harm your skin a little in the long term yet the benefits outweigh the harm for most patients. But understanding the variability in response is key to safe and effective therapy.
There is a widespread curiosity about red hair, and we are often asked questions about colouration – only some of which we have answers to. When were the first red heads? (Red-haired variants of the MC1R gene probably arose about 20-40 000 years ago.) What is the genetic relationship between bright red, strawberry blonde and auburn hair? (Not entirely clear as yet.) And is the red hair gene a 'Celtic gene' – as is widely supposed? (Not really, but it is safe to say that – a few rare exceptions aside - all red heads are MC1R variants that derive from European populations; the prevalence of these alleles is highest in Celtic countries.)
So there is lots more to find out about the genes involved in skin and hair colour. Once we have unpicked their undoubtedly complex relationships, we should have many more answers about the origins, history and subtleties of red hair itself, and about in the development, control and health of the skin in general.
Red hair is such a distinctive characteristic that one can imagine, in some future world, two red heads meeting up on some distant planet and the conversation quickly turning to their place of birth! Whether or not they were both of Celtic blood, they could be sure that at least one of their genes was remarkably similar.
Jonathan L Rees is Professor of Dermatology at the University of Edinburgh.
Valverde P et al. Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nature Genetics 1995;11(3):328. Abstract