The Language of the Genes

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The Language of the Genes Page 5

by Steve Jones


  It has, nevertheless, become possible to read ancestral genes directly. Some ancient DNA, like that of the Easter Islanders, whose civilization was destroyed by constant warfare and ecological vandalism, has no equivalent in the modern world and remains, like their enigmatic statues, as the sole evidence of a people who left no posterity. Sometimes, it adds to the clues of the present. Agriculture began in Japan with the Jonion people, about ten thousand years ago, but they also spent much of their time as hunters. Farming did not take oft as a way of life, with rice as a staple diet, until the Yayoi tribes who followed them, thousands of years later. Rice was brought by the Chinese, and the Japanese argue about how many of their genes entered the country with the crop. Many believe that the immigrants drove out most of the natives; that people moved, rather than ideas. However, DNA extracted from a two-thousand-year-old Chinese burial site links its inhabitants with modern Chinese, but not with the fossil DNA of the extinct Japanese. It proves that few mainland-ers made the journey. Instead, the locals of two millennia ago, much like their modern descendants, picked up and used a new technology invented in a foreign land. Modern Japan, on the other hand, does have biological links with the Chinese, so that a movement from the mainland had an impact much later.

  Some ancestral voices are particularly fluent in telling the story of the past. Mitochondria are small energy-producing structures in the cell. Each has its own piece of DNA, a closed circle of about sixteen thousand DNA bases, quite distinct from that in the cell nucleus. Eggs are full of mitochondria but those in sperm are killed off as they enter the egg. As a result, such genes are inherited almost exclusively through females. Like Jewishness, they pass from mothers to daughters and sons, but daughters alone pass them on to the next generation.

  Kvery family, every nation and every continent can trace descent from its mitochondrial Eve, a woman (needless to say, one of many alive at the same time) upon whom all their female lineages converge. Sometimes she lived not long ago: in New Zealand, lor iiist.iin.i-, iifiirly all Maoris share the same mitochondrial identity, hulling that just a few women founded their nation a thousand years ago. A world family tree based on mitochondria finds its roots in Africa, with more diversity in that continent than anywhere else. To track more recent paths of migration shows that mitochondria are an accurate record of history: thus, in the New World, native mitochondria have a tie with those of Siberia, confirming an ancient pattern of migration.

  Shared genes link New Zealand, Siberia and the rest of the world to an African ancestor. The first modern human appeared in Africa over a hundred thousand years ago, in the continent that gave rise to most of our pre-human kin and of the apes to whom we claim affinity. A few of these African relatives from a deeper branch of the tree are alive today. One, the chimpanzee, has always seemed a near neighbour; and Koko (an inhabitant of the Gombe Stream Reserve) was the first animal to have an obituary in The Times.

  As any literate teenager knows, Tarzan of the Apes was proved to be the son of Lord Greystoke by virtue of the inky fingermarks in a childhood notebook. Galton had shown that chimpanzees have fingerprints that look much like those of a human being. Chimps and men, they prove,share genes. A joint heritage goes beyond the fingertips. A distinguished geneticist of the 1940s once tested whether chimps share our variation in the ability to taste the bitter chemical PROP by feeding it to three of the inhabitants of London Zoo. Two swallowed the drink with every sign of delight, but the third spat the liquid all over the famous professor as further evidence of common ancestry.

  The biological affinity goes much further. Apes have blood groups like our own, their chromosomes are almost identical, and a test of the overall similarity of DN A shows that humans share ninety-eight per cent of their genetic material with chimpanzees. We trace relatedness to the rest of the animal kingdom as well, with about a quarter of our genes similar to others in remote places among the insects or the jellyfish. Mice and men have much more in common, including dozens ol inherited diseases. We share even more genes with rabbits and plenty with remote branches of existence, from bacteria to yeasts to bananas. All living creatures seem to need a set of 'housekeeping genes* that do the basic work of the cell, and many of the seven hundred such structures are shared. Most have changed little since they began. An unkind experiment in which more and more of the five hundred genes in a simple bacterium were destroyed showed that it needs, at an absolute minimum, three hundred or so; nearly all of which have parallels in our own DNA. This common core shows that the most unlikely beings speak the same genetic language.

  Pharaoh Psamtik the First, who flourished in the seventh century before Christ, searched for the first word of all. He put a baby in the care of a dumb nurse and noted the sounds it made. One word was (or seemed to be) 'becos', the Phrygian for bread, suggesting to Psamtik that the Phrygians (who lived in what is modern Turkey) were the first people of all. A computer search through the millions of DNA letters now sequenced from dozens of organisms also hints at a shared structure from bacteria to humans; the father (or mother) of all genes, that might have persisted since life began. The scientist who published the ur-sequence has turned the information to a useful end. Assigning musical notes to each DNA letter he used them as a theme for a 'symphony of life'.

  Gene sharing, from bacteria to humans, proves the unity of existence. It also defines the limits ot what biology can say. A chimp may share ninety-eight per cent of its DNA with ourselves but it is not ninety-eight per cent human: it is not human at all — it is a chimp. And docs the tact that we have genes in common with a mouse, or a banana, say anything about human nature? Some claim that genes will tell us what we really are. The idea is absurd.

  One gene is found in a certain form in men, but a different one in all other apes. It codes for a molecule on the cell surface much involved in communication between cells, brain cells more than most. Perhaps this is the gene — or one of the genes — that makes us human. Its message spelt out in the four DNA letters, A, G, C and T starts like this: AACCGGCAGACAT… Altogether, it has three thousand letters. Together they contain an important part of the tedious biological story of being a man or woman rather than a chimpanzee or gorilla. Needless to say, that ancestral bulletin does nothing to tell us — or apes — what it means to be part of humankind. That calls for a lot more than a sequence of DNA bases and lies outside the realm of science altogether.

  St Bede — whose writings are the best source of information about England before the eighth century — had a powerful metaphor for existence. To him human existence was 'As if when on a winter's night you sit feasting with your eaidormen and rhegns, a single sparrow should fly swiftly into the hall, and coming in at one door instantly fly out through another. In that time in which it is indoors it is indeed not touched by the fury of the winter, but yet, this smallest space of calmness being passed almost in a flash, from winter going into winter again, it is lost to your eyes. Somewhat like this appears the life of man; but of what follows or what went before, we are utterly ignorant.' His allegory was a religious one but has a biological parallel. Genes have a memory of their own. To read it gives new hope of looking beyond the hall into which our own brief existence is confined. It allows us to learn what went before in the life of out own species; to guess ar what happened much earlier, and even ro speculate about what fate may hold for generations yet to come.

  Chapter Two THE RULES OF THE GAME

  It is always painful to watch an unfamiliar game and to try to work out what is going on. Although I livi'tl in the United States for several years, and although tin* sport is now shown on British television, I have almost no idea how American football works. There is a clear general desire to score, but how play stops and starts and why the spectators cheer at odd moments remains a closed book. A deep lack of interest in balf games helps in my case, but cricket is equally dull to sporting enthusiasts from other countries. They just do not understand the rules.

  The rules of the game known as sexual reprodu
ction are not obvious from its results. As a consequence, how inheritance works was a closed book until quite recently. Part of the problem is that the way sex works is so different from how it seems that it ought to. It seems obvious that a character acquired by a parent must be passed on to the next generation. After all, blacksmiths' children tend to be muscular and those of criminals less than honest. In the Bible, Jacob, when allowed to choose striped kids from Laban's herd of goats, put striped sticks near the parents as they mated in the hope of increasing the number available. Later, pregnant women looked on pictures of saints and avoided people with deformities. It took a series of painful trials in which generations of mice were deprived of their tails to show that acquired characters were not in fact inherited. Of course, Jews had been doing the same experiment for thousands of years.

  Another potent myth about inheritance is that the characters of a mother and a father pass to their blood, which is mixed in their offspring. Children are, as a result, a blend of the attributes of their parents. This idea — a sort of genetics of the average — copes quite well with traits such as height or weight but fails to explain why a child may look like a distant relative rather than its father or mother. The idea lasted until just a few years ago. The stud book is the record kept by racehorse breeders. A mare who had boriu1;i foal by mating with a non-stud stallion was struck off as her blood was deemed to be polluted. Indeed, n survey of elderly women in Bristol showed that half believed in the chance of a woman having a black baby if she had sex with a biack man many years before. The croiu-s ot the west country, like the breeders of horses, had never managed to work out the instructions for the reproductive game.

  The only section of The Origin of Species which does not make good reading today is Chapter Five, 'Laws of Variation'. Darwin got it wrong and, after much agonising, suggested that the organs of parents passed material to the blood and then to sperm and egg. Children were, he thought, intermediate between those who produced them. Such a mode of inheritance would be fatal to the idea of evolution. The problem was pointed out by Fleeming Jen-kin, the first Professor of Engineering at the University of Edinburgh. Writing in 1867 — and with a sturdy disregard of today's proprieties — Jenkin imagined ka white man wrecked on an island inhabited by negroes. Suppose him to possess the physical strength, energy and ability of a dominant white race. There does not follow the conclusion that after a… number of generations the inhabitants of the island will be white. Our shipwrecked hero would probably become king;… he would have a great many wives, mil L'hiklrrn.. much superior in average intelligence to the negroes, but can anyone believe that the whole island will gradually acquire a white or even a yellow population? A highly favoured white cannot blanch a nation of negroes.'

  Jenkin saw that the attributes of a distant ancestor, valuable as they might be, are of little help to later generations if bloods mix. Characters would then blend over the years until their effects disappear. I lowevcr useful an ink drop in a gallon of water might be at some time in the future it is impossible to get it back from;i sm^lr mixi-d drop. Genetics by blending means that any adv.iiii.i^iousch.iiMc-ter would be diluted out in the next generation. Fortunately, the blood myth is wrong.

  It was shot down by (ialtnn himself. He transfused blood from a black rabbit to a white to see if the latter had black offspring. It did not. Inheritance by dilution had been disproved, but Galton had nothing to put in its place.

  Unknown to either Darwin or to his cousin the rules of genetics had already been worked out by another biological genius. Gregor Mendel lived in Bohemia and published in a rather obscure scientific journal, the Transactions of the Brunn Natural History Society. His breakthrough was overlooked for thirty-five years after it was published in 1866. Mendel, an Augustinian monk, attempted a science degree but failed to complete it. Like Darwin and Galton he suffered from bouts of depression which prevented him from working for months at a time. Nevertheless, he persisted with his experiments. He found that the inherited message is transmitted according to a simple set of regulations — the grammar of the genes. Later in his career (and setting a precedent for the present age) he was unable to continue with research because of the pressures of administration. The study of inheritance came to a halt for almost half a century.

  Grammar is always more tedious than vocabulary, but cannot be avoided. The rest of this chapter explores the basic rules of genetics. Those who teach the subject still have an obsession with Mendel and his peas and I make no excuse for having them as a first course.

  Mendel made a conceptual breakthrough. Instead of (like his predecessors) working on traits such as height or weight (which could only be measured) Mendel was more or less the first biologist to count anything. This put him on the road to his great discovery.

  Peas, like many garden plants, exist in true-breeding lines within which all individuals look the same. Different lines are distinct in characters such as seed shape (which can be round or wrinkled) and seed colour, which may be yellow or green. Peas also have the advantage that each plant carries both male and female organs. Using a small brush it is possible to fertilise any female flower with pollen from any male. Even a male flower from the same plant can be used. The process, a kind of botanical incest, is called self-fertilisation.

  Mendel added pollen (male germ cells) from a line with yellow peas to the female part of a flower from a green pea line. In the next generation he got an unexpected result. Instead of all the offspring being intermediate, all the plants in the new generation looked like one of the parents and not the other. They all had yellow peas. This is not at all what would be expected if the 'blood' of the two lines was blended into a yellowish-green mixture.

  The next step was to self-fertilise these first-generation yellow plants; in other words to expose their eggs to pollen from the same individual. That gave another unforeseen outcome. Both the original colours, yellow and green, reappeared in the next generation. Whatever it was that produced green could still do so, even though it had spent time within a plant with yellow peas. This did not fit at all with the idea that the different properties of each parent were blended together. Inheritance was, his experiment showed, based on particles rather than fluids.

  Mendel did more. He added up the numbers of yellow and green peas in each generation. In the first generation (the offspring of the crossed pure lines) all the plants had yellow peas. In the second, obtained by self-fertilising the yellow plants from the first generation, there were always, on the average, three yellows to one green. From this simple result, Mendel deduced the fundamental rule ol genetics.

  Pea colour was, he thought, controlled by pairs of factors (or genes, as they became known). Kadi adult plant had two factors for pea colour, but pollen or egg received only one. On fertilisation — when pollen met egg — a new plant with two factors (or genes) was reborn. The colour of the peas was determined by what the plant inherited. In the original pure lines all individuals carried either two *yellow' or two 'green' versions of the seed colour gene. As a result, crosses within a pure line gave a new family of plants identical to their parents.

  When pollen from one pure line fertilised eggs from a different line new plants were produced with two different factors, one from each parent. In Mendel's experiment these plants looked yellow although each carried a hidden set of instructions for making green peas. In other words, the effects of the yellow version were concealing those of the green. The factor for yellow is, we say, dominant to that for green, which is recessive.

  Plants with both variants make two kinds of pollen or egg. Half carry the instructions for making green peas and half for yellow. There are hence four ways in which pollen and egg can be brought together when two plants of this kind are mated, or a single one self-fertilised. One quarter of fertilisations involve yellow with yellow, one quarter green with green; and two quarters-one half-yellow with green.

  Mendel had already shown that yellow with green produces an individual with yellow peas. Yellow with
yellow, needless to say, produces plants with yellow peas, and in a plant with two green factors the pea is green. The ratio of colours in this second generation is therefore three yellow to one green. Mendel worked backwards from this ratio to define his basic rule of inheritance.

  Mendel made crosses using many different characters — flower colour, plant height and pea shape — and found that the same ratios applied to each. He also tested the inheritance of pairs of characters considered together. For example, plants with yellow and smooth peas were crossed with others with green and wrinkled peas. His law applied again. Patterns of inheritance of colour were not influenced by those for shape. From this he deduced that separate genes (rather than alternative forms of the same one) must be involved for each attribute. Both for distinct forms of the same trait {yellow or green colour, for example) and for quite different ones (such as colour and shape) inheritance was based on the segregation of physical units. Mendel was the first to prove that offspring are not the average of their parents and that genetics is based on differences rather than similarities.

  Biologists since his day have delighted in picking over his results (and accusing him of fraud because they may fit his theories too well). They argue about what he thought his factors were, and speculate about why his work was ignored. Whatever lies behind its long obscurity, Mendel's result was rediscovered by plant breeders in the first year of the twentieth century and was soon found to apply to hundreds of characters in both animals and plants. Mendel had the good luck, or the genius, needed to be right where all his predecessors had been wrong. No science traces its origin to a single individual more directly than does genetics, and Mendel's work is still the foundation of the whole enormous subject which it has become.

 

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