Language of the Genes

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to the developing cmbryo. MilOch,,"d, .. \ h.\ vl·.1 p.1llern of inheritance quite different fro m tho," III Ihe Ilucleus . They do not bother with sex, but instea d arc passed down rhe female line. Sperm are busy little things, with a long journey to make, and are powered by many mitochondria. On fertilisation these are degraded, so that only the mother's genes are passed on. In the body, too, mitochondria are transmitted quite passively, each cell dividing its population among its descendants. Their DNA contains the history of the world's women, with almost no male interference. Queen Elizabeth the Second's mitochondrial DNA descends, not from Queen Victoria (her ancestor through the male line) but from Victoria's less eminent contemporary Anne Caroline, who died in r88r. Mitochondria, small as they are, are the site of an impressive variety of diseases. Their sixteen and a half tho usand DNA bases -less than a hundredth of the whole sequence - were, a century after the death of Anne Caroline, the first to be read off. Every cell contains a thousand or so of the structures. They are the great factories of metabolism; places where food - the fuel of life - is burned. Mitochondrial genes code for just thirteen proteins, and about twice that number of the molecules that transfer information from the DNA to where proteins are made.

49

The Language of the Genes They are more liable to error than are others. Some of the mistakes pass between generations, while others build up in the body itself as it ages. Some of the two hundred known fau lts involve single changes in the DNA, others the destruction of whole lengths of genetic material. Some are frequent: thus, a certain change in one mitochondrial gene is present in about one in seven thousand births. Mitochondrial disease involves many symptoms: deafness, blindness, or damage to muscles or the brain. Certain forms of diabetes are due to mitochondria l errors, as is an inherited muscle weakness and drooping of the eyelids. Different patients in the sa me family may have distinct problems; perhaps deafne,s in one child and brain damage in another. All this come. from the role of mitochondria in burning energy and from rh eir random shuffling as cells divide. An egg may carry both normal and abnormalmitochondria. If, in an embryo, th ose wirh an error become by chance common in the cell lines that make brain tissue, that organ suffers; if in cells that code for insulin, then diabetes is the result. Mothers pass such genes to sons and daughters, but only daughters pass it to the next generation; a pattern quire different from sex-linked inheritance. These, then, are the rules of rhe genetical game. From here on, the rest is molecular biology: mechanics rather than physics. The notion that life is chemistry came first from humans. In 1902, JUSt twO years a&er the rediscovery of Mendelism, the English physician Sir Archibald Garrod noticed that a disease called alkaptonuria - at the time thought to be due to an intestinal worm - was more frequent in the children of parents who shared a recent ancestor than in those of unrelated people. Its symptoms, a darkening of the urine and the earwax, together with arthritis, followed that of a recessive. The disease was, he thought, due to an inherited failure in one of the pathways of metabolism, what he called a "chemical sporr' (Darwin's 50

The RI/les of the Game another way. Chromosomes are paired bodies in the cell which appear as dark strands. Most of the chromosomes of the two sexes look similar but one pair - the sex chromosomes - are different. Females have two large X chromosomes; males a single X and a much smaller Y. Morgan noticed that the pattern of inheritance of eye colour followed that of the X chromosome. Males, with just a single copy of the X (which corncs from their mother, the father providing the Y) always lookcu lik e their mother. In females, the copy of rh e X chromO"'IllC (rom the mother was accompanied by a mat ching X frolll Ihe father. In a cross between white-eyed mOl h c r~ ,Ind red-eycd fathers, the female offspring have one X chro mosome bearing 'white' and another bearing 'red'. Just as Mendel would have expected, they have eyes like only one of the parems, in this case the one with red eyes. The eye colour gene and the X chromosome hence show the same pattern of inheritance. Morgan suggested that this meant that the gene for eye colour was actually on the X chromosome. He called this pattern 'sex·linkage'. Chromosomes were already candidates as the bearers of genes as, like Mendel's hypothetical panicles, their number is halved in sperm and egg compared to body cells. Everyone has forty-six chromosomes in each body cell. Twenty-two of these are paired, but the sex chromosomes, X and Y, are distinct. Because the Y carries few genes, in males the ordinary rules of Mendelian dominance and recessivity do not apply. Any gene on the single X will show its effects in a male, whether or not it is recessive in females. The inheritance of human colour blindness is just like that of Drosophila eye colour. When a colour-blind man marries a normal woman none of his children is affected, but a colour-blind woman whose husband has normal vision passes on the condition to all her sons but none of

47

The Language of the Genes her daughters. Because all males with the abnormal X show its effects (while in most females the gene is hidd en by one for norma l vision) the trait is commone r in boys than in girls. Many other abnorma lities show the same pattern. Sex-linkage leads to interesting differences between the sexes. For the X chromosome, fema les carry two cop ies of eac h gene, but males on ly one. As a result, women contain more genetic in forma ti on thon do men. Because of the two different sensors for the perception of red controlled by a gene on th e X chromosome, many women must carry both red receptors, each sensitive to a slightly different poine in the spectrum. Males are limi ted to just one. As a result, some women have a wider range of sensual experience for colour at least - than is ava ilable to any man. Whatever the merits of see in g the world in a different way, women have a potential problem with sex-linkage. Any excess of a chromosome as la rge as the X is normally fatal. How do fema les cope with two, when just one contains all the information needed to make a normal human being (or a male)? The answer is unexpected. In almost every cell in a woman's body one or other of her twO X chromosomes is switched off. Tortoiseshell cats have a mottled appearance, which comes from small groups of yellow and black hairs mixed together. All tortoiseshells are females and are the offspring of a cross in which one parent passes on a gene for black and the other transmits one for yellow hair. Because the coat-colour gene is sex-linked about half the skin cells of the kitten switch off the X carrying the black variant and the remainder that for yel low . The coat is a mix of the two types of hair, the size of the patches varying from cat to cat. The same happens in humans. If a woman has a colourblind son, she must herself have one normal and one abnorIllal colour receptor. When a tiny beam of red o r gree ll

The Rilles of the Game own word for a deviation from the norm). It was the first of many inborn errors of metabolism. The actual gene itself was found juSt four years before the century ended. The key to its discovery showed how wide the genetical net must spread. An identical was found in a fungus, and that piece of damaged DNA used to search out its human equivalent. What genes arc made o f came from the discovery it was possible to change the shape of h.1Clnial colonies by inserting a 'tran sforming principll"

l'X 11 .1p huma n settlement 193, [95-6, >00

Huntington's Disease 188 Australopithecus afarell5is 163

babies, birrh weights 306-7 Bach, Johann Sebasrian 95

bacteria u8, 239. 244, 27(-2,

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Basque people 205. 217-18 Bearrice, Princess 83 Bccanus (philosopher) 222 Bede, St 35 Bengali language 173, 216, 220 Bentham, Jerem y 19 Be rri llon, Alpho nse I Bible references 19,37, 105, 160, 163, ' 75 , 19r, 200-r, 208, 2r6, 222, 256 Bilharzia (schistosomiasis) 240,

'44 birth con trol 303-4. 309 Black Death 239 blood apes and monkeys clorring 84-5 genetic variation 24-5, 178-9, 206, 262-3 group systems 29, 45, 57.169, 206,25 1 ,26 1 mixing of blood myth 38-9 red cells 73-6,92, T26, 186, 247 see also haemoglobin see also diseases; haemophiliaj malaria; sick le-cell Blumenbach, Johann 258 Boswell, James 15 1 brain, human 171,254 Brazil 18rh C. tra nsportation 27 early human sires [76, [99 see also American Indians; Yanomamo people Britain r8th C. immigrants 27-3 ( albinism 43 disease 245 former epidemics 241-3

Index DNA finge rpri nting L, 3, 33 generic studies 85-6, 129, T38 language and dia lects 2.[5, 2.1 8, 220

life expeccancy 303-4. 308 marriage trends 180-1, 304, 3 12 - T4 rad iation hazards 90- I . 302 surnames I7S, 180 Bronte, Emily 100, 148 Brown, Louise 14 Brunclleschi, Fil ippo 277 bubonic plagu e 24 I Bushme n 266 Butler, Samuel 17 1,300

cancer 76,90,92,95. IOL-3. 105, 120-1, T32-3. 138,228,233, 276, 290, 303, 308 Ca rnegie, Andrew 6 Carroll, Lewis 227 cats 48, 97-8 , 280 Ca ucasia ns 213, 221, 256, 258, ,63 cells an tigens 23-4, 63, I OO, 189, 234, 250 cell divisio n 5 I labo ratory cu lture 295-6 see also chromoso mes Cel ts 260- 1 Centre for Germ inal Choice 94 Chambers, Robert 253 Charles V, Emperor 2 22 Chemical Week f23 chemica ls mutation haza rds 9 1, 102-3 chicken-pox 240 Chile, mummies [ 99 chimney-swee ps 102

chimpanzees see apes and monkeys Ch ina agricu lture revolution 202-3 disease 246 ea rly humans 32, 163-6, 194 early med icine eye sha pe 233 genetic variation 208, 2 I 3 language 73, 218, 220 rice cultivation 206, 219 surnames 178 chloroq uine 28 4 cholera 244 chromoso mes deficiencies 76-80 structu re and pa ttern L69 X a nd Y in fer tilisation Q-15, 46-7. 145-7 inherited disease and sexlinkage 39-4 3, 4 7-8, 55-8, 62-3,66-8,87- 8, 10 9- 10 link with su rn ames 175-6 see also DNA; genes; mutation C hu rc hill, Winston 9 ci ties a nd city states 211 Cleopatra-Beren ike III 180 climate, changes and genetic effects 20[, 204,23 0-5 cl oni ng see DNA Clov is culture 199 Cold Spring Harbor Labora tory (formerly Eugenics Record Office) 8, 1 ' 7 co lour co lour-blindness ix 21-2, 47-9, 61, 122, 169 eyes, hai r and skin 2 T, 30. 46-7, r52, 233, 254-5, 261 -2 peas 40-7. 55 Combe Grenal cave (France) 194

329

The Language of the Genes Descent of Man (Darwi n) r 52., 160 desertification of land 193 230 diabetes r08, 12.6, 134-7 diagnosis by proxy J (9-2.0 diarrhoea 2.44. 2.51 diphtheria 2.41

Coolidge, Pres ident Ca lvin 2.59 Cosi ma, Sr 256 cowpox

272

Creationists 159 crime 95. 128 Cro-MaAnoli Man 166, [95.2. 18, loll

Cromwell, Oliver 24 6 Cyprus d isease 126, 247. 305-6 human settlemenr 194 proscribed marriages 1 8 1 cystic fibrosis 66-9.12.1,125. 130-3. 139. 263, 288-9. 30 r,

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dacrylomancy .18 Damian, Sf 2-56 da nci ng mania 24 1 Darwin, Cha rles b lood mixing fal lacy 38 Malrhus' influence 192 natural selection theory '5 1 -2.,225- 8 Socia l Darwinism r08 theories o n huma n o rigin 148-9. 1 60,166-8 theories saved by generics 4 3 voyage of Beagle 5, 186 and Darwinism xi 51. 268-70,

300 Darwin, George 180 Davenport, Cha rl es B. 8, 117 Dawkins, Richard 228 DDT 284 dearh, changing pattern 243. 306 - 8 Denma rk, Down's syndrome testing 128

disease agent of natural selectio n 2.36, 2.39-52. contagious and infectious

30 5- 6 deficiency [18 immunity and resistance 63, 100,2.39,2.89 inherited chromosomal mapping 64-9 genetic mutations 2.0, 82-4, 98-9, [00, 12.7-30, 132.-7 mental illness 10, 83, 87 and sex-linkage 39-43, 47-5 1 ,55-8,62.-3 national tendencies 12.6, 12.8 tests and treatmenr 11 8 DNA a lpha bet x double helix xii, xv 5 r, (70 fingerprinting [ 8, 43, 2.62., 264-6 fossil records 32., (67-8 hybrid isation 169-70 mapping xiii-xv 54-5, 6r-5. 68-75,8 4,93, l U, '45, 2.62.-3 mitochondrial 32.-3,49-5 1, 188 of abo riginal peop le 189, 19 6 -7, 199.2. 0 5 replication and cloning xiii 52., 60-1,7 1 , 75. 278,286-9 8 sam pl es 3

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Index tracing ancestry and identity 20, 26-9, [75-6, 179-80, r89 see also chromosomes; disease; genes; Human Genome Project; mutation Dolly the Cloned Sheep xiii 286-7, 294-5, 2.97 Down, Langdon 2.54 Down's Syndrome 128, 254. 305 Drosophila meianogaster see fr uit flies drugs anti -cancer agencs 276, 2.78-9 Biopi racy 2.78 medicinal 187. 2.78 response ro 98, 15}. 22.8 Duffy blood groups system 29 dwarves 129. 302dyslex ia 222 dystrophy see mu scular dystrophy

Einstein, Albert 176 electrophoresis 58- 9 Elemo-Dravidian language 22.1 Elior, Gcorge: Daniel Dem"dd

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Easter Island 32, 197,219 Ebola fever 2.43 Ecuador 279 Edwa rd , Duke of Kent 82 Edwa rd VII, King 14 1-2 eggs and sperm ch romosomes 13-1 5, 46-7 destructive effect of age 303 ferti lisation failure 89-90,92, 12.7, [46. 183 in-vitro ferti lisation 292.-3, 295 mitochondria 32-3. 49-51, 146 role of inheritance 13- 15, 46-7, 82, 141 lise of PCR in spe rm ce ll s 6l Egypr disease 240, 246 pharaohs and DNA relics J 1-2., 180

Elizabeth II , Queen 49 Engels. Friedrich 192 English Sweat 241 enzymes 59-60, 6.l, 104, 112, 122, 125. 234, 24 7. 265. 279 Eskimos (Inuit) 198, 2.20, 2.24. 2.3 1- 2 Essay Oil the Principles of Poplliation (Malthus) 192 Ethiopia 1"9 early human sites 163,165 Etruscan Empire 212-1 3. 2. 18 eugenics movemems 5- 10, 16-r8, 87.116- 17, 12.j, 259-60 Eugenics Record Office 8, 11 7 see also Cold Spri ng Harbor Laboratory Europe 18(h C. Ame rindian immigrants 31 ability to digest 236 disease 242-3 mediaeval epidemics 24 r early farming 202-5, 219 evolution of Homo sapiens r66, 194-5,19 8 genetic structure and diversity 206, 212, 261, 2.65 languages 2 14 - 16, 2J8-19 lowering of marriage age 304-5 see also indiv idual countries evo lution applied evo lution 2. 68-85 early ideas 37-8. 159-66 economic development 191-207, "0

33 I

The Language of the Genes evo lu rion - cont.

'founder effect' 186-8 generic drift T76 harmonic mean 184

natural selection

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2)8- 40, 2.44. 1-46, 2.49, 2.5 1-2., 2.57, 2261-2, 307, 30 9 puncruated equilibrium 167

skull shapes 256-8 of Utopia 299-316

food abilities ro digest 2.36 diet as agenr of genetic change 200-2,23 6 potatoes 14.1-4, 277, 293 see also farming fossi ls 160-8, 173, 193 fragile X syndrome 87-8, l19. 12 4

France ea rl y human si tes 166, 194-5.

eyes

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bl indness and glaucoma

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colour-blindness ix 21-2, 47-9. 61

Factors VII, VIH, IX 84-5, 88, 272fa nning Darwin 's theory 2.2.5-8

developmen t 32, 200-7. 208-10, 219. 268 genetic engi neering and Green Revolurion 269-71,273-7.

280-3 ' Round-Up' 276, 2.82 Fiji, measles epidemic 239 fingerprints

chimps and humans r, ). 33 dacry lomancy I' 8 generic

262

fingers, abnormalities 43-4. 61 Finland early farming 2.03. 206 langua ge 2. [6 Fischer, Eugene fish 147, I 7l

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FISH (Fluorescent In·Situ Hybridisation) 61

genes and language 2 15-17 Gcncthon project 62. marriage trends 304-5 twin births J05 Freud, Sigmund 97. J8S fruit flies (Drosophila meJaflogaster) 46-7. 55, 62., 64. 71, 234, 3 ro Fulani people 236

Galapagos Islands 186 Galton Francis (-3.95-6, 300 and Basque language 2 17- 18 blood experiments 39 chim ps' fi ngerprints 3. 33 eugenics movement 5-11, r6-18, I r6, T28 search for ideal woman 15 2 -3 Ga lton Laboratory 5. 117 Garrod, Sir Archibald 50 genes economic and socia l forces [2. ge ne shari ng 35 ge neric imprinting 43 link with crime 46 link with past 2.0. 3 J. 31

33 2

Index see also chromosomes; disease; DNA; genetics; muration Gene-thon project 62 generics basic rules 40-5 2 early hi sto ry xi, xiv -xv 20. 3 4 , 38 genetic engineering and gene therapy 65-7 mass screening I 18, I l. l - } , 13.h 1 3 6 - 8 ,1 55 moder n image and progress I I - l l.. 15. 17, 1.5 , 117- 18 nature ve rsus nurture 95 -7, 11 1- 12

and race theory see eugenics recombination 269. 280-1 trends for future 123-4, 126, 286-98 George III, King 83, 186 George IV, King 260 germ line therapy 29 1 Ge rmany ea rly human sites 166, ' 94-5, ' 98 euge nics movementS 10-11, 11 0, 12 8

language 216, 220 lowering of age of reproduction 30 4 Nazis and Jews 10-11,259-60 Ghana, deformities in chi ldren 1 2 Gi lbe", \'(I.S .• 68 glaucoma 1.0 Gobi neau, Josep h 258 Goldwyn, Sa m I 17 Gran t, Madison 259 Greece ancicnr civi lization 203, 205,

disease 24 [ modern excha nges with Turks 2 [3

Haeckel, Ernst 9, 259 haem oglobin sick lc·cdlmut ation 27-8, 45. 9 2 , 24 7-9. 28 9

haemophi lia ix 81.-6, 89. 101,297 Ha iti, white ancestry in populatio n 255 Haley, Alex, and Roots 1.7, 29 Harrima n, Mrs E.H. 8 Hawa iian Islands fru it fl ies J 7 1 human settlemenr 197, 1.19 hay fever 99 heart disease 45, 105, [08 , L Il. , 13 2 , 134, ' 37, }08 Hemings, Sally 29 Hemochromatosis 125 Henry I, King 216 Heriditary Ge,t;us (Ga lton ) 2, 5. 95 Herodotus 53, 57 Heycrdahl, Thor L9 7, 258 Hippoc rates 24 l, 246 Hitler, Adolf 10, 259 Hittite language 2 18 Holl and, ge neric di sease 99, 119,

. 86-8 !-fame, Lord Alexa nder 20 H omo (sp