by Bryan Sykes
A
B
O
Iceland
19
7
74
Norway
31
6
62
Ireland
18
7
75
By any token, the only conclusion from the blood-group composition is that Iceland was not settled from Norway at all. Far more likely, from the blood-group results, is a wholesale settlement from Ireland or somewhere else with similar blood-group proportions, like parts of Scotland. As we will see in a later chapter, there is at least a partial explanation for this discrepancy, but that is not the main message I want to get across here.
Faced with this disagreement in the blood results, instead of having the confidence to overturn the theory of Norse settlement, Mourant tries to rationalize by finding Scandinavian ‘homelands’ that might heal the discrepancy. He cites parts of western Norway around Trondelag that have a blood-group composition a little more like Iceland than the rest of the country, then reports an isolated population in northern Sweden in the province of Vasterbotten with an even more Icelandic composition. Northern Sweden isn’t even close to the Atlantic and no traditions link it to the settlement of Iceland. Mourant then highlights an old settlement at Settesdal in southern Norway with ‘Icelandic’ blood-group compositions. Finally, to resolve this awkward disagreement, he suggests that the modern-day Scandinavians are the descendants of people moving in from the south and east who displaced the Vikings and drove them to settle in Iceland.
All of these attempts to resolve the disparity between, on the one hand, mountains of cultural and historical evidence on the Scandinavian origin of the Icelanders, and the blood-group results on the other, highlight a fundamental weakness in the value of using blood groups to infer origins. If the results from the labs agree with what you already believe about the origins or make-up of people, then there is a cosy feeling that the genetics, archaeology and history are all in agreement with each other. But when they do not there is a temptation to fabricate an agreement with increasingly unlikely scenarios, as with Iceland.
I suspect the same has been done in the south-west corner of Wales. The southern part of Pembrokeshire surrounding the deep-water inlet of Milford Haven delights in the sobriquet of ‘Little England beyond Wales’, a reference to the anglicized place-names and the long use of the English as opposed to the Welsh language. The levels of group A in this small region of Wales are 5–10 per cent higher than in the surrounding areas. It is known that Henry I forcibly transferred a colony of Flemish refugees fleeing political repression in Holland and Belgium to the area in the early twelfth century. The high levels of blood group A have been attributed to this historical influx and are often quoted in popular accounts as a classic success of blood grouping confirming history. This is despite the levels of blood group A in the Low Countries not being particularly high. However, a very different explanation was favoured by the Welsh scientist Morgan Watkin, the man who originally noticed the high proportion of group A in parts of Pembrokeshire. He put it down to a substantial Viking settlement in the region, despite the fact that there is very little in the way of archaeology or place-names to support it. But the fact remains that, even after thousands of blood samples from Wales and hundreds of thousands from all over Britain and Ireland, it is still impossible to decide whether the unusual blood-group composition of this part of Wales was caused by rampaging Vikings or by a few cartloads of Belgians.
The root of the problem is that, despite there being vast amounts of very reliable data, blood groups just do not have the power to distinguish these two theories, nor the power to propose new ones that might fly in the face of historical or archaeological evidence. Blood groups, despite the advantage of objectivity, are a very blunt instrument indeed with which to dissect the genetic history of a relatively small region like the Isles. Fortunately, we can sharpen our genetic scalpel. Now we can do something that William Boyd, Arthur Mourant and the others could not. We can move to the next stage and take the last step towards the final arbiter of inheritance. We can move to the DNA itself.
6
THE SILENT MESSENGERS
Whatever their shortcomings as a guide to the past, the fact that blood groups are 100 per cent genetic makes it self-evident that they are inherited from ancestors. They are not DNA, but they are the expression of DNA. You may like to compare the relationship between DNA and blood groups like this. When you listen to a piece of music you are not hearing the written notes themselves, but the expression of the notes as interpreted by the musicians. Our inherited features, both those we notice, like hair and eye colour, and those, like blood groups, that we need tests to reveal, are the music we hear. The DNA is the equivalent of the notes on the sheet, which the musicians are reading to produce the music.
Arthur Mourant and his fellow blood-groupers were too early to see the sheet music on which the blood-group notes were written, but they knew from the way it was inherited in families that it must be very simple. The four different blood groups A, B, AB and O are the expression of three versions of a single gene, a single piece of DNA. Once it became possible to read the notes behind the music, the true cause of the blood groups was revealed to be very slight changes in the DNA of the blood-group gene itself. DNA is a coded message in the form of a sequence of four slightly different chemicals attached to each other. If you think of it as a very long string of beads, where each bead is one of these DNA chemicals, then that will give you an idea of what a strand of DNA looks like. Now imagine that there are four different colours of bead on the string, each one representing one of the four DNA chemical bases, as they are called. You can see how the string of beads might become a code purely by virtue of the sequence in which the different coloured beads are arranged. The DNA of the blood-group gene is about 1,000 beads, or bases, long.
Though it calls the shots, DNA doesn’t actually do the work in the body, just as the notes on a sheet of music need musicians to be heard. DNA is the code that tells cells, all of which contain DNA, what to do. Just as notes on a musical score tell the orchestra what to play, DNA tells cells which proteins to make. And it is proteins that build and run the body. Proteins are made up of amino-acids arranged in a specific linear sequence and it is this sequence of amino-acids that gives the protein its particular properties. No two proteins are the same. The protein collagen, for example, has a very strong and rigid structure which it needs to do its job in strengthening bones and teeth. That strength is a direct result of the way the amino-acids are arranged, just as the oxygen-carrying capacity of haemoglobin comes about by the particular sequence of its own amino-acids. The same goes for the blood-group protein that sits in the membrane of red blood cells. It is all down to the sequence of amino-acids.
The DNA instructs the cell how to make proteins through the coded instructions held in the sequence of the coloured beads on the string. Cells know how to interpret this code and how to translate the DNA sequence into the amino-acid sequence of a protein. The differences between alternative versions of the same gene, which are what produce the three different blood groups, are caused by mutations. This is when, very rarely, there is an error in copying the DNA. A bead suddenly changes colour and the DNA sequence changes slightly. Cells read the new sequence like the mindless automata they are. They don’t realize that they are now producing a slightly different version of the protein, which may have different properties. They just do as they are told.
Most mutations happen when DNA is being copied. Since every cell contains a full set of DNA, it has to be copied every time a cell divides. We all start off as a single cell, a fertilized egg, and grow from that by cell division to an adult with 10 million billion cells, so there is an enormous amount of DNA copying going on and plenty of opportunity for DNA mutation. However, the fidelity of copying DNA is absolutely fantastic, and of course it needs to be. If it were as poor as the average photocopier, by
the time the fertilized egg had divided and divided to produce at first an embryo, then a foetus, then a baby, the DNA instructions would become so fuzzy that every child would be born with every genetic disease under the sun–if he or she ever got born at all. To prevent this happening, there are proofreading and editing mechanisms which scan the newly copied DNA to make sure it matches the original sequence. All of this is to reduce the chance of mutation. And in this we are very successful. On average, a DNA base mutates only once in every thousand million times it is copied. Even so, this minuscule error rate is enough to produce all the genetic variation in our own species and in every other living creature that we see in the world around us. Mutation is the life-blood of evolution.
Without mutation, there simply is no evolution. Most of the time mutation, even when it occurs, has absolutely no effect. Very occasionally, though, mutations do drastically affect the working of whatever protein the gene is in charge of–and that is how devastating inherited diseases can begin their life. In my earlier career as a medical geneticist, working as I did with inherited bone diseases, I saw many patients whose bones would fracture at the slightest knock. They were badly deformed and often unable to walk–but often astonishingly cheerful and optimistic. Their disease, called osteogenesis imperfecta, a very serious form of brittle-bone disease, was caused by one of these random mutations in a bone collagen gene. But instead of making a harmless change to the DNA sequence, in these patients the mutation had hit a crucial DNA base in the collagen gene. The mutations in these patients, even though they change just a single DNA base, completely alter the structure of the collagen, turning it from an extremely strong protein into the biological equivalent of putty.
Mutations can be good, bad or indifferent. Most are indifferent, like the mutations which produce the different blood groups. A few are bad, as in the brittle-bone patients. Vanishingly few are good, in the sense that they improve the way the protein works. On the whole the bad mutations are eliminated pretty swiftly as people with inherited diseases die or have fewer children. Good mutations can find themselves increasing from one generation to the next if they aid the survival of the people that carry them or help them have more children. Indifferent mutations, and they are in the majority, have no influence one way or the other on survival or success in breeding. They just get passed from one generation to the next, their fate entirely out of their hands. They risk elimination if they end up in someone who has no children or can do well if they find themselves in a large family. They might lead less dramatic lives than the mutations that bring success or devastation. But it is these, the silent passengers of evolution, that are its most articulate chroniclers. This is precisely because they cause no ripples, they are unseen by natural selection and are neither promoted nor destroyed by its attentions. But nowadays, thanks to the breakthroughs of the last twenty years, we can see them in the read-out from the DNA analyser. And we can use them to trace our ancestry.
While Arthur Mourant did what he could with the very limited number of blood groups, there is almost no limit to the amount of different DNA sequences that we are now able to detect. It is this massive increase in our ability to distinguish one person’s DNA from another which has made all the difference in our ability to trace our ancestry and discover our genetic origins. But with all this choice, which were going to be the best genes to concentrate on, and why?
During my work on ancient bones I wanted to give myself the best chance of recovering DNA so I chose to focus on a rather unusual piece of DNA. Most of our DNA is contained within the cell nucleus, attached to tiny thread-like structures called chromosomes. This is where the collagen genes, the haemoglobin genes and the blood-group genes reside. For all of them, as for most of our ‘nuclear’ genes, we have only two copies in each cell, one from each of our parents. However, outside the cell nucleus, though still inside the cell membrane, there is a different source of DNA altogether. In the liquid cytoplasm surrounding the nucleus are tiny particles called mitochondria. These particles control many of the steps in aerobic metabolism and they have an interesting evolutionary history, having once been free-living bacteria. From our point of view at the time, where this DNA had come from and what it did was unimportant. What counted was that there was far more of it in the average cell, maybe a thousand times more, than the DNA of any of the nuclear genes. If only a few cells survived in the ancient bones, targeting mitochondrial DNA would maximize our chances. It turned out to be the right decision, and we found mitochondrial DNA in the first batch of bones we tried. It is still extremely hard to recover nuclear genes from ancient specimens, while getting out the mitochondrial DNA is now almost routine.
As well as its abundance in each cell, mitochondrial DNA (or mDNA for short) has two other outstanding properties to recommend it as a window into the human past. Firstly, it mutates about twenty times faster than regular nuclear DNA. The error-checking mechanisms in mDNA are much less vigilant than they are in the nucleus. Our species has been around for about 150,000 years and, although this seems to us like a very long time, the nuclear DNA mutation rate is so low that the vast majority of it is completely unchanged since that time. In a typical stretch of nuclear DNA 1,000 bases long, nineteen out of twenty people will have exactly the same sequence. Within the same sized stretch of mDNA, almost everyone is different.
The second excellent feature of mDNA is its very unusual inheritance pattern. As we have seen, most of the nuclear genes are inherited equally from both parents. You have received one copy of each nuclear gene from your mother’s egg and one from your father’s fertilizing sperm. But you got all of your mDNA only from your mother, and for one very simple reason. Compared to sperm, eggs are huge cells, bulging with cytoplasm, which is crammed with a quarter of a million mitochondria. Sperm do have a few mitochondria, about a hundred, in what is called the mid-piece, which connects the sperm head, containing all the nuclear DNA, to the tail. The thrashing tail needs the aerobic energy output of the mitochondria in the mid-piece to fuel its progress towards the egg.
But once the successful sperm penetrates the egg to deliver its precious load of nuclear DNA, its mitochondria are not only vastly outnumbered but are deliberately destroyed. This is why, although the fertilized egg contains nuclear DNA from both father and mother, all the mitochondria, and so all the mitochondrial DNA, is from the mother.
The process is repeated generation after generation after generation. Nuclear DNA comes from the father and mother, mDNA only from the mother. Consider your own mDNA for a moment. It is powering your aerobic metabolism in every cell–from the cells in your retina which collect the focused image from the page, to the muscles in your arm that turn the pages, to the cells that are burning fuel to keep you warm. All these functions are controlled by your mDNA which, because of its unusual inheritance, you have got only from your mother. Who got it from her mother. Who got it from her mother and so on. At any time in the past, be it 100, 1,000, even 10,000 years ago, there was only one woman alive at the time from whom you have inherited your mDNA. Even though I have known this for years it still amazes me to think about it.
The combination of plenty of genetic variation with its matrilineal inheritance makes mDNA the perfect guide to the human past. But it needs to be complemented, because it can tell only one side of the story. Mitochondrial DNA can only tell the history of women. Very fortunately, there is a piece of DNA which can do the same for men. This companion guide to our genetic history could not be more different. This is the piece of DNA that is entirely male. It is the Y-chromosome.
Inside the nucleus of every human cell are a total of forty-six chromosomes. Forty-four out of the forty-six carry on them the great majority of the 10,000 genes that build and run our bodies. They include the blood-group, collagen and haemoglobin genes we have already met and many, many more. They direct almost everything, from aspects of our physical appearance like eye and hair colour, to our immune systems, to our innate psychological and emotional make-up. I
n everybody, male and female, these forty-four chromosomes come in pairs and are inherited from both parents, twenty-two from one, twenty-two from the other.
The other two chromosomes, called X and Y, are different in that they are not always inherited from both parents. And not everybody has both of them. Females have two X-chromosomes and men have one X-chromosome and one Y-chromosome. In the official notation of genetics, women are XX and men are XY. However, despite what I have come to appreciate that most people believe, the X-chromosome has nothing directly to do with sex. Women are not women because they possess two X chromosomes–the truth is far more interesting. Women are female because they don’t have a Y-chromosome. How can that be?
Looked at under the microscope, the X and Y chromosomes look quite different. Both are the same shape, like tiny threads, but the X-chromosome is about five times as long. The differences between X and Y don’t stop there. Thanks to the output from the Human Genome Project we now have the DNA sequence for both chromosomes. The larger X-chromosome is very like the other forty-four chromosomes. It carries about 1,000 genes which control a range of different cellular activities. The Y-chromosome, on the other hand, is a genetic wreck with only twenty-seven genes that appear to be working properly. The rest of the chromosome is made up of long stretches of so-called ‘junk’ DNA. This is DNA that, unlike genes that do things, has no known function. It is just there. The evolutionary implications for this tremendous difference between X- and Y-chromosomes are fascinating, but not especially relevant here. What does matter is that just one of the twenty-seven active genes on the Y-chromosome, the sex gene, is what makes males.
