by Bryan Sykes
The next leap forward came from the mathematical amalgamation of the vast amount of data that had accumulated from decades of research on individual systems like the different blood groups. This was accomplished by the man who has dominated the field for the past thirty years, Luigi Luca Cavalli-Sforza. We will meet him again later. Cavalli-Sforza, working with the Cambridge statistician Anthony Edwards, achieved this amalgamation using the earliest punched-card computing machines. By averaging across several genetic systems at once they managed to eliminate most of the bizarre and counter-intuitive conclusions that had discredited the anthropological applications of blood groups when they were worked on one at a time. The weakness of using just a single system was that two populations, like the Russians and the Malagasy, could end up with the same gene frequency just by chance rather than because of a common ancestry. This was far less likely to happen if several genes were compared, because the impact of a misleading result from one of them would be diluted out by the effect of the others. There were to be no more Russian invasions of Madagascar. None the less, the underlying principle remained the same. In an evolutionary sense, populations with similar gene frequencies were more likely to be closely related to each other than populations whose gene frequencies were very different.
Anthony Edwards explained his thinking in an ingenious article in New Scientist in 1965. He imagines a tribe that carries with it a pole along which are arrayed 100 discs which are either black or white. Every year, one disc, chosen at random, is changed to the other colour. When the tribe splits into two groups, each group takes with it a copy of the pole with the discs in their current order. The following year they each make one of the random changes to the discs. The next year they make another, the next year another and so on, continuing the custom of one random change every year. Since the changes they make are completely random, the order of the discs on the two poles becomes more and more dissimilar as each year passes. It follows that if you were to look at the poles carried by the two tribes you could estimate how long ago, in a relative sense, they separated from each other by the differences in the order of the black and white discs. Providing an absolute date was very difficult from the gene frequency data alone, but the comparative separation between the two tribes, known as the genetic distance, was a useful measure of their common ancestry. The bigger the genetic distance between them, the longer they had spent apart.
This was a clever image of the process of genetic change, called genetic drift, brought about by the random survival and extinction of genes as they pass from one generation to the next. This process leads to bigger and bigger differences in the frequencies of genes as time passes. Just like the order of discs in Edwards’ analogy, gene frequencies can be used to backtrack and work out how long ago two groups of people were once together as a single population. These groups could be villages, tribes or whole populations, and there is no limit to the number of groups that can be analysed in this way. If you do it for the whole world, the outcome is a diagram like Figure 1 overleaf.
Figure 1
Along the right-hand side we have several ‘populations’ (I have picked two examples from each continent) and along the bottom is the genetic distance/time axis. This is what is called a population tree where the lines trace, from left to right, the estimated order in which ‘populations’ evolved and split from one another, as reconstructed from the assimilated frequencies of many different genes. At first glance, many of the groupings look quite sensible. The two European populations, the English and the Italians, are close together on two short ‘branches’ of the tree. The two native American tribes are connected together with their closest relatives in Asia, as we would expect if the first Americans crossed the Bering land bridge from Siberia to Alaska. The two populations from Africa are on a different branch from the rest of the world, which correctly emphasizes that continent’s great antiquity as the cradle of human evolution. This is a much more sensible-looking tree than can be drawn from the First World War blood group data which, as well as allying Russia and Madagascar, entirely missed the importance of Africa. The reason for this, as noted earlier, is that the odd quirks that arose by chance with a single system, like the ABO blood groups, get ironed out by amalgamating the results from several different genes.
Edwards acknowledged that ‘The resultant evolutionary trees will certainly not provide the last word on human evolution,’ and offered the diagrams as a way of providing the genetic information in an understandable form. Unfortunately, the population trees first drawn with this admirable and modest intention were over-interpreted and became a source of contention. Among the several reasons for this is just the way they appear. They do look as if they are real evolutionary trees and have often been portrayed as exactly that. They could only be true evolutionary trees if human evolution really were a succession of population fissions along the lines of the splits that Edwards explains in his metaphor of the tribes with their poles and discs. Then and only then would the nodes, the points on the tree from which two lines diverge, represent a real entity. These would be the populations that existed before the splits, the proto-populations. But is that what really happened in human evolution? For instance, in the European part of the tree, was there ever such a thing as the proto-Anglo-Italian population which divided, never to meet again, and became the modern inhabitants of England and Italy? That might have been the case if the English and Italians became two different species as soon as they split and could never interbreed again. But they can, and they do, and they always have done. As we will discover later in the book, humans just did not evolve like this.
Perhaps the most serious objection to these trees is that their construction demands that the things at the end of the trees, the populations, be objectively defined. This process in itself segregates people into groups in ways that can tend to perpetuate racial classifications. It gives some sort of overall genetic number to something that does not really exist. There are certainly people who live in Japan and Tibet, but there is no genetic meaning to the population of Tibet or Japan, taken as a whole. As this book will show, objectively defined races simply do not exist. Even Arthur Mourant realized that fact nearly fifty years ago, when he wrote: ‘Rather does a study of blood groups show a heterogeneity in the proudest nation and support the view that the races of the present day are but temporary integrations in the constant process of…mixing that marks the history of every living species.’ The temptation to classify the human species into categories which have no objective basis is an inevitable but regrettable consequence of the gene frequency system when it is taken too far. For several years the study of human genetics got firmly bogged down in the intellectually pointless (and morally dangerous) morass of constructing ever more detailed classifications of human population groups.
Fortunately, there was a way out of this impasse. The break-out came with the publication of a scientific paper in Nature in January 1987 by the veteran US evolutionary biochemist, the late Allan Wilson, and two of his students, Rebecca Cann and Mark Stoneking, entitled ‘Mitochondrial DNA and human evolution’. The centrepiece of this article was a diagram which bears a superficial resemblance to the trees I have just been criticizing. I have reproduced a small section of it here in Figure 2, with only sixteen individuals instead of the 134 in the original paper.
It is indeed an evolutionary tree; but this time the diagram means something. On the right of the tree the symbols at the tips of the branches represent not populations but the sixteen individuals that I have selected to illustrate the point, sixteen people from four different parts of the world: Africans, Asians, Europeans and Papuans from New Guinea. The first improvement over the other trees is that, unlike populations, there is no argument about whether people exist or not. They clearly do. The other improvement is that the nodes on the tree are also real people and not some hypothetical concept like a ‘proto-population’. They represent the last common ancestors of the two people who branch off from that point. The li
nes that connect the sixteen people on the diagram are drawn to reflect genetic differences between them in one very special gene called mitochondrial DNA whose unusual and useful properties I will introduce shortly. For reasons I shall explain in the next chapter, if two people have very similar mitochondrial DNA then they are more closely related, with respect to this gene, than two people with very different mitochondrial DNA. They have a common ancestor who lived more recently in the past, and so are joined by shorter branches on the diagram. People with very different mitochondrial DNA share a more remote common ancestor and are linked by longer branches.
Figure 2
To see how this works we can use again the metaphor of the tribe with its pole holding black and white discs. But this time the pole is the mitochondrial DNA and the tribe that split in two is a person who has two children. Both children inherit the same mitochondrial DNA, the genetic equivalent of the same pattern of discs on the pole. When they have their own children they pass on the mitochondrial DNA to them, and so it goes on down the generations. Very occasionally, random changes, called mutations, occur in the mitochondrial DNA which alter it a little bit at a time. These occur quite by chance when the DNA is being copied as cells divide. As time passes, more random changes are added to the DNA, which are then retained and passed on to future generations. Very slowly, the mitochondrial DNA of the descendants of that first individual, their common ancestor, becomes more and more different as more random mutations are introduced one at a time.
The lines on the tree in Figure 2 are reconstructions of the relationships among these sixteen people, worked out from the differences in their mitochondrial DNA, the exact nature of which we will examine shortly. But look for the moment at the tree itself. The deep trunk at the top has four Africans at the tips, while the other deep trunk contains individuals from the rest of the world and one more African. Within this ‘rest of the world’ trunk, close branches sometimes connect people from the same part of the world, like the Asians and Papuans at the top or the Europeans at the bottom. But they also sometimes connect individuals from different places, like the branch near the middle that links a Papuan with an Asian and two Europeans. What’s going on? The deep split between the exclusively African ‘trunk’ and the rest of the world is another confirmation of the antiquity of Africa which the population trees also pick up. The confusion in the ‘rest of the world’ trunk is confirmation of exactly what Arthur Mourant had in mind. It is ‘the mixing that marks the history of every living species’. Small wonder, then, that this diagram threw a very large spanner in the works of the population tree aficionados. It shows that genetically related individuals are cropping up all over the place, in all the wrong populations. You just cannot sustain the fundamental idea of a population being a separate biological and genetic unit if individuals within one population have their closest relatives within another.
Moreover, as we shall see in greater detail later on, by using the mutation process just described we can estimate the rate at which mitochondrial DNA changes with time. This means we can work out the timescales involved. When we do that, all the branches and the trunks converge to a single point, the ‘root’ of the tree, at about 150,000 years ago. This had to mean that the whole of the human species was much younger and more closely related than many people thought.
The impact of ‘Mitochondrial DNA and human evolution’ was dramatic. It came down very firmly on one side of the argument about a fundamental question of human evolution. For many years there had been an intense and polarized debate on the origins of modern humans, based on different interpretations of fossil skeletons, mainly the skull. Both sides agreed that modern Homo sapiens, the species to which we all belong, originated in Africa. Both sides also agreed that an earlier type of human, called Homo erectus, was an evolutionary intermediate between ourselves and much older and more ape-like fossils. Homo erectus first appeared in Africa about two million years ago and by one million years ago, or perhaps even earlier, it had spread out to the warmer parts of the Old World. Homo erectus fossils have been found from Europe in the west to China and Indonesia in the east.
All that was – and is – agreed by both sides of the argument. What divides them is whether or not there was a much more recent spread of modern humans from Africa. The ‘Out of Africa’ school think there was, about 100,000 years ago, and that these new humans, our own Homo sapiens, completely replaced Homo erectus throughout its range. The opposing school of thought, the multi-regionalists, see clues in the fossils that suggest to them that Homo sapiens evolved directly from their local Homo erectus populations. This would mean that modern Chinese, for example, are directly descended from Chinese Homo erectus, and modern Europeans are similarly evolved from European Homo erectus, rather than being descendants of Homo sapiens who migrated from Africa. In the multi-regional scheme a modern European and a modern Chinese would have last shared a common ancestor at least one million years ago, while in the ‘Out of Africa’ scenario they would be linked very much more recently.
What the mitochondrial gene tree did was to introduce an objective time-depth measurement into the equation for the first time. It showed quite clearly that the common mitochondrial ancestor of all modern humans lived only about 150,000 years ago. This fitted in very well with the ‘Out of Africa’ theory and was enthusiastically welcomed by its supporters. But it came as a severe shock to the multi-regionalists. If all modern humans were related back to a common ancestor as recently as 150,000 years ago, they could not possibly have evolved in different parts of the world from local populations of Homo erectus that had been in place for well over a million years. Though the multi-regionalists, being thoroughly modern humans themselves, have refused to accept defeat, the mitochondrial gene tree dealt a wounding blow to their theory from which it has not yet recovered.
For us, it was great news. Mitochondrial DNA was catapulted by this controversy into its position as the prime molecular interpreter of the human past. A surge of research effort was bound to follow in laboratories all over the world. And that meant there would be lots of data with which we could compare our own results. If we were going to put the results from the old bones into a modern context, then we could not do better than use mitochondrial DNA.
4
THE SPECIAL MESSENGER
Mitochondria are tiny structures that exist within every cell. They are not in the cell nucleus, the tiny bag in the middle of the cell which contains the chromosomes, but outside it in what is called the cytoplasm. Their job is to help cells use oxygen to produce energy. The more vigorous the cell, the more energy it needs and so the more mitochondria it contains. Cells from active tissues like muscle, nerve and brain contain up to one thousand mitochondria each.
Each mitochondrion is enclosed within a membrane. Arranged in an elaborate structure within the membrane are all the enzymes required for the final stage of aerobic metabolism. This is the part where the fuel we take in as food is burnt in a sea of oxygen. There are no flames and all the oxygen is dissolved, but it is as much a piece of combustion as what happens in a gas fire or a car engine. Fuel and oxygen combine to produce energy. Fires and engines produce their energy as heat and light. Mitochondria do not give off light when they burn fuel but they do heat up – it is partly the heat given off by mitochondria that keeps us warm. However, the main output is a high-energy molecule called ATP, which is used by the body to run virtually everything, from the contraction of heart muscles, to the nerves in your retina that is reading this page, to the cells in your brain that are interpreting it.
Buried right in the middle of each mitochondrion is a tiny piece of DNA, a mini-chromosome only sixteen and a half thousand bases in length. This is minuscule compared to the total of three thousand million bases in the chromosomes of the nucleus. Finding DNA in mitochondria at all was a big surprise. And it is very peculiar stuff. For a start, the double helix of this DNA is formed into a circle. Bacteria and other micro-organisms have circular chromosomes, bu
t not complex multi-cellular organisms and certainly not humans. The next surprise was that the genetic code in mitochondrial DNA is slightly different from the one that is used in the nuclear chromosomes. Mitochondrial genes hold the code for the oxygen-capturing enzymes that do the work in mitochondria. However, many genes that govern the workings of the mitochondria are firmly embedded within the chromosomes of the nucleus.
How did this all come about? The current explanation is stunning. It is thought that mitochondria were once free-living bacteria that, hundreds of millions of years ago, invaded more advanced cells and took up residence there. You could call them parasites, or you could call their relationship with the cells symbiotic, with both cells and mitochondria doing something for each other. Cells got a great boost from being able to use oxygen. A cell can create much more high-energy ATP from the same amount of fuel using oxygen than it can without it. For their part, the mitochondria evidently found life within the cell more comfortable than outside. Very slowly, over millions of years, some of the mitochondrial genes were transferred to the nucleus, where they remain. This means mitochondria are now trapped within cells and could not return to the outside world even if they wanted to. They have become genetically institutionalized. Even now you can see the evidence of gene transfers between mitochondria and nucleus that didn’t work out. The nuclear chromosomes are littered with broken fragments of mitochondrial genes that have moved across to the nucleus over the course of evolution. They can’t do anything because they are not intact. So they just sit there, as molecular fossils, a reminder of failed transfers in the past.
