by Steve Jones
As well as the differences between chimpanzees and humans, each varies to some degree from place to place. The chimpanzee is strongly subdivided at the DNA level. It has three distinct ‘races’, in West, in Central and in Eastern Africa. The central group is about three times as diverse as is the western. The extent and pattern of diversity hints that the western and central groups split half a million years ago, while the eastern segment found an identity no more than fifty thousand years before the present. Humans are in comparison tedious, with far less change among the world’s populations than among the chimp races.
Sequencing machines are now hard at work on more of our relatives. Rhesus macaques are small monkeys common in India, Burma and elsewhere in the Far East, and widely used in medical research. They share rather more than nine-tenths of their DNA with humans. Many of the shifts involve - as in the chimpanzee - changes in the order or numbers of copies of particular segments. The animals eat lots of fruit, and genes that help digest sugar have been multiplied compared with our own. Some of their genes are in a form that in humans leads to disaster. The mutation for the rare inborn disease known as phenylketonuria - a fatal inability to deal with certain foods - is the standard version found in macaques. Might some dietary change have rendered lethal to ourselves an enzyme once useful in our ancestors? A group of genes that predisposes to cancer in humans helps make sperm in macaques. Why does a sexual helper in monkeys cause our cells to run out of control? If we knew, we might have a new weapon against the disease.
Men and chimps, and men and macaques, have changed a lot since their paths parted. The fossils and the genes combine to say when and how their evolutionary divergence, and others from long before, took place. The daring assumption that DNA accumulates error at a regular rate, combined with information on dates from the scattered fossils of our distant ancestors, hints that the first true mammals evolved around a hundred and twenty-five million years ago. The double helix also shows that chimps, orangs, humans and monkeys cluster together in a class that includes lemurs and rabbits but does not admit horses, dogs, bats and many other hairy creatures. The kinship of men, lemurs, rabbits and the rest is revealed by a certain piece of mobile DNA that hops around the genome. It has been inserted in the same place in all those creatures, proof that they share a common ancestor distinct from that of their furry fellows.
Genes, fossils and geography combine to suggest that the primates as a group began around eighty-five million years before the present. The monkeys and apes split not long after that - which means that their true origin was on the vast continent of Gondwana rather than on the fragments that we now recognise as Africa, Madagascar and India. The macaque set off on its own pathway around twenty-five million years before today. The split between ourselves and our close relatives is, it appears, quite recent. The limited genetic divergence between chimpanzees and humans suggests that they separated five to seven million years ago. Their common ancestor broke away from the gorilla line a million years or more earlier, and that trio split from the orang-utan branch about six million years before that.
There is more to evolution than the random accumulation of mistakes. Darwin’s machine may not have a long-term direction, but it can swerve around obstacles as they arise. At the wheel is natural selection: inherited differences in the ability to pass on genes. In its long and arduous journey, selection’s ability to cope with whatever turns up has led to the physical differences between men and chimps, men and macaques and, for that matter, men and rabbits or bats. Each diverged from the same shared ancestor, and each has faced its own challenges and, with the help of natural selection, found its own unique set of solutions.
Not all of us leave descendants, but we all have ancestors. To transmit its DNA to the present day, each of them had to survive, find a mate and produce offspring. An infinity of their contemporaries tripped at one or other of life’s hurdles and left no posterity. The Descent of Man speculates about how selection might have acted upon the human line and that of our relatives but it offered little direct evidence of its action. Sexual choice was, its author thought, important (and he began but abandoned a project to discover whether blondes were less likely to marry than were brunettes) but his case for its role was far weaker than that for animals and plants presented in The Origin of Species.
The evidence for lust as an engine of human evolution is still patchy at best, but that for other forms of natural selection is now compelling. The process has been - and still is - at work in our own lineage. It leaves its footprints upon the genome in many ways, some obvious and some less so. Sometimes, natural selection can be seen in action. More often, the evidence of its labours is indirect and gives no hint of how and why it was busy.
Long-term trends such as the increase in human brain size over millions of years show what selection can achieve, given time. The grand patterns of genes across the globe are also proof of its powers.
None are grander than the shifts in man’s physical appearance from place to place, which are more marked than those in any other large mammal. The story of how the trends in human hair and skin colour evolved has emerged, albeit in several shades of grey, as evidence of how selection causes change and of how subtle and unexpected its actions can be.
Homo sapiens and his immediate ancestors moved not long ago from white to black, and in some places back to white again. Chimps have rather pale skins, although their faces may become tanned. African skin is, in contrast, dusky, which means that darkness is relatively new to the human line. In religious art, Adam and Eve are always shown as light-skinned. Given the looks of today’s Middle Easterners that was doubtful at best. The first modern humans, a hundred thousand years and more ago, were certainly black.
DNA hints that our new and swarthy appearance arose about a million years before the present. At just that time, our ancestors began to move from the forests to the sun-baked savannahs. Long legs and arms and a distinct nose (not found in chimps) also emerged, perhaps to cope with life in the sun. In addition, we lost our hair - perhaps to cool down - and dark skin was favoured as it protected against the harmful effects of ultraviolet light. The colour of the skin turns on the amount of a pigment called melanin.
The first hint about Eve’s complexion came not from people but fish. The zebrafish is often used to study embryonic development. A certain mutant lacks the dark stripes that give the animal its name and is almost transparent. The gene responsible has been tracked down in both its mutated and its normal version. A search through our own DNA reveals an almost precise match; so close, indeed, that the human gene will reinstate a zebrafish’s stripes when injected into a mutant embryo. The enzyme it makes shows a large shift in structure across the globe. A certain building block - an amino acid - is present at one point along the protein chain in 98 per cent of Africans, while in 99 per cent of Europeans it is replaced by a different version. The form found in Africa makes far more pigment than does the alternative. A large part of the shift in appearance between the inhabitants of the two continents hence emerges from a change in a single letter of the genome. The length of DNA involved varies not at all in its functional section throughout Africa, as a hint that dark skin was strongly favoured when it first arose and that any later changes have been removed by selection. Europeans are more diverse, with a variety of forms of the crucial protein that give rise to black, blonde or red hair and to dark or to almost translucent skin. Fossil DNA shows that Neanderthals had their own, different, mutation in that segment of the genome, so that they too were probably white.
In a twist to the tale, the light skins of China and Japan evolved in a different way. The gene that bleached the Europeans played no part, for the locals bear the African, rather than the European form. The people of the Far East paled in their own fashion, and evolution picked up changes in quite a different set of genes. A certain segment of DNA, when it goes wrong, causes albinism - a loss of skin pigment - in Europeans. The loss of melanin from Asian skin comes, in large par
t, from a mutation in a different section of that gene. Several other parts of the melanin factory differ in structure between Africa, Asia and Europe. Most have small but noticeable effects on colour, which is why the children of a marriage between an African and a European vary from dark to light and do not resemble either of their parents exactly.
The earliest modern Europeans and Asians of forty or fifty thousand years ago were almost certainly black. Even the French cave-painters at Lascaux may have had that complexion, for their images of the aurochs, the giant oxen, are reddish, while those of the men who hunt them are darker. The first Englishmen - those who followed the ice as it melted - reached these islands thirteen thousand years ago. They too may have retained their African colour when they set foot on their new nation’s shores.
Why does it pay to be black in Benin but fair in Folkestone? Everything we know about melanin is positive, while fair skins seem at first sight to do more harm than good. Melanin protects against skin cancer - and fifty thousand people develop that in Britain each year. Two thousand die. Light skin burns easily. That may sound trivial, but sunburn makes it hard to sweat and easy to overheat, which brings dangers of its own. In addition, melanin reduces the destruction of vitamins in the blood as they are exposed to the harsh rays of the sun. Fair-skinned women who sunbathe have reduced levels of a vitamin called folic acid, and their newborn children pay the price, for a shortage of the stuff causes birth defects. Given the problems of pale skin, something powerful must have changed us on the journey from the azure firmament of the tropics to the gloom of British skies.
Another vitamin was to blame. Vitamin D helps build bones. It controls the levels of calcium and phosphorus in the blood for it helps the gut to absorb them and rescues quantities of each element that would otherwise be lost in the urine. Oily fish, eggs and mushrooms are rich in the stuff and many governments now add it to milk or flour to promote their citizens’ health. Vitamin D can, in addition, be made in the skin through the action of ultraviolet light on a form of cholesterol.
To do the job, the light must get in and melanin keeps it out. Africans have to spend several hours a day in bright sunlight to make enough vitamin D to stay healthy, but northern Europeans who expose their arms, head and shoulders for fifteen minutes at a midsummer noon can make enough to meet their needs.
A shortage of the stuff puts children in danger of the soft-bone disease rickets, which leads to a curved spine or legs and can cause severe disability. Sufferers may also experience seizures and spasms - a side-effect of calcium shortage - which can end in heart failure. Nine out of ten infants in Victoria’s smoky and starved cities showed signs of the illness and rickets is still the commonest non-infectious childhood disease in the world.
Most young black people in the United States have low levels of the crucial vitamin and the condition is, as a result, three times more common among black Americans than in their white fellow citizens. As a youth the athlete O. J. Simpson suffered from rickets and wore home-made leg braces. On this side of the Atlantic, my own generation was saved by free cod-liver oil, but the modern world is not so lucky. In Britain, soft bones are back. A third of Asian and Afro-Caribbean children are short of vitamin D (for the former the fact that they are not allowed to uncover themselves is in part to blame). Severe deficiency is nine times more frequent in that group than in Europeans and one in a hundred of their children show signs of illness. Girls do worse, which is bad news later on, for their pelvis narrows and they find it harder to give birth. There have even been cases of shortage in affluent white children allowed to play in the sunshine - but protected from the dangers of ultraviolet with sunscreen.
The magic substance also helps to hold diabetes, arthritis, muscular dystrophy and heart disease at bay and protects against the spread of certain cancers, with a higher rate of lung and bowel cancer in cloudy places. Any change in skin colour that helped to generate more of the vitamin must have been most helpful on mankind’s journey into the gloom. Natural selection noticed the new mutations at once and in cloudy places fair skin soon took over.
Selection has lead to many other upheavals in human DNA. Many of them emerged from shifts in our habits as we moved from ape to early human, and to modern man. Migration, shifts in diet and the rise of towns and cities all led to genetic change.
For nine-tenths of our history as a species, most people saw fewer people in their lifetimes than an average westerner now does on his way to work. Agriculture led to a population explosion, and Homo sapiens is now ten thousand times more abundant than is any other mammal of his size. In a world of pathogens and parasites, abundance is an expensive luxury. Epidemics have often cut our species down to size. They need large populations to sustain themselves, and migrants to spread the infection. The Plague of Justinian, which began in Constantinople in AD 541, put paid to a quarter of the people of the Eastern Mediterranean. The Black Death spread along the Silk Road from China in the fourteenth century and returned again and again to the teeming and filthy cities of the west. Two out of three Europeans died. Sickness is potent fuel for selection and many genes respond to it.
One illness shows its power better than any other. A third of the world’s population is exposed to malaria, half a billion are infected and the disease kills five people a minute. The real attack began about ten thousand years ago, when men moved into - and cut down - tropical forests at a time of warm, wet weather. That helped mosquitoes to breed and the parasite to spread.
In Kenyan families, poor conditions - a marshy spot, too much rain, too many children - explain some of the variation in individual risk of illness, but genetic differences are behind at least a third of the overall chance of ending up in hospital. Some variants have a large influence and are soon picked up by evolution while others are more subtle. The most important involve changes in the red blood pigment, haemoglobin. A quarter of a billion people bear at least a single copy of a mutated version of the molecule. The best known is sickle-cell, a simple change in the DNA alphabet. The haemoglobin of those with two copies forms long crystals in parts of the body low in oxygen. The red cells take up a crescent shape that restricts circulation and causes pain, heart disease and worse. Those with a single version of the altered message are healthy, with half the risk of fever if infected and a ten times lower chance of serious illness. A third of all Africans are in that situation and the gene is common in southern Europe, in the Middle East and in India. It has arisen on at least four different occasions. Other such changes give a lesser protection in countries such as Bangladesh, while deletions of long or short sections of DNA do the same in the Middle East and Oceania. Once again, those who carry two copies of a damaged gene pay a severe price while people with just one are protected.
Many other genetic changes have been pressed into service against that unpleasant illness. The parasite uses a certain red-cell enzyme to fuel its machinery. Hundreds of millions of people bear a defective version, but in return gain a defence. A certain form of the parasite cannot get into cells that lack a particular attachment site. Almost all West Africans have this variant. Elsewhere, a change in the shape of the red cell baffles the agent of infection, while the high salt and iron levels in African blood also fend it off. Dozens of sections of the DNA are implicated in the fight against malaria and many, no doubt, remain to be discovered. Large or small, each has been picked up by the selection, which, just as in the evolution of pale skins in Europe and Asia, has cobbled together a response step by step.
Natural selection is always poised to deal with enemies as they arise. Wherever it works, it leaves evidence, often indirect, that it has passed by. Some changes in DNA alter the structure of proteins while others do not. The ratio between the two is a crude test of its actions, for useful sections of the genome are more likely to accumulate change under the influence of selection than are the non-functional parts. On that criterion, our lineage has experienced rather less of its attentions than has that of the chimpanzee.
Another clue to the action of Darwin’s agent comes from the blocks of genetic variants packed close to each other along each chromosome. As a favoured gene - a new anti-malaria mutation, perhaps, or a change in skin colour - is picked up and becomes more common, it will drag along sections of DNA on either side. The stronger and more recent the selection, the longer the segment that accompanies it. In Africa, both the gene for black skin colour and that for sickle-cell sit in the middle of great sections of double helix that vary scarcely at all from person to person. That pattern hints that in each case the new mutation was seized upon at once and spread fast.
In time such uniform blocks of DNA are broken up by the random reshuffling of genes that takes place when sperm and egg are formed, but the process can take a long time. A length of DNA that is identical from person to person within the generally diverse genome is hence evidence that selection is, or has been, at work. The human and chimp genomes each have thousands of such segments. One gene in sixty among the chimps bears that Darwinian mark but only half as many in humans, as proof that we have coped with new challenges in a manner that our close relative cannot. Man’s ability to modify the environment to suit his needs has weakened the hammer blows of nature. Anti-malaria drugs now do what could be achieved only by expensive mutations. Thousands of years ago, our skin responded fast to a shift in climate, with a genetic change; but most people, black or white, now protect themselves against the sun in quite a different way, with clothes.