261 What gives us our skin colours? Africans differ from Europeans, and East Asians are known to differ in the structure and density of their melanosomes (Szabó et al. 1969; Toda et al. 1972), but very little is known about the genetics – except for a hint it might have something to do with the P gene (Sturm et al. 1998). See Linnaeus (1758) pp.20–1 for his diagnosis of the human species; a translation is given by Robins (1991) p.171.
262 For nearly half a century. The history of race-classification in South Africa is discussed by Posel (2001). Rita Hoefling’s story is told by Joseph and Godson (1988).
265 Life growth hormone, melanotropins. Red hair and obesity are caused by mutations in POMC (176830), a gene that encodes the ?-MSH and ACTH precusor (Krude et al. 1998).
266 Yet not all redheads are fat. Red hair (266300) caused by recessive mutations in the MC1R gene (155555) (Robbins et al. 1993; Valverde et al. 1995; Smith et al. 1998; Flanagan et al. 2000; Healy et al. 2001). Besides the general plausibility arguments that I have given as to whether red hair has been selected or not (Darwin 1871, 1981 volume 2 pp.316–405; Robins 1991 pp.59–72) and is therefore properly thought of as a mutation or polymorphism, there are also elaborate statistical tests which can sometimes detect historical patterns of selection. Such tests have been applied to MC1R, but they are inconclusive (Rana et al. 1999; Harding et al. 2000).
268 Pale, and proud of it. For a detailed discussion of the pre-PRC history of Chinese anthropology and eugenic thought see Dikötter (1992, 1997, 1998). For a study of Ainu hairiness see Harvey and Broth well (1969).
269 In the collection of the Capodimonte. For the history and iconography of the Gonsalvus family see Aldrovandi (1642); Siebold (1878); Zapperi (1995); Haupt et al. (1990) pp.92–7 and, especially, Hertel (2001).
273 In 1826 John Crawfurd, British diplomat and naturalist. For the history of Shwe-Maong and his family see Crawfurd (1827); Yule (1858) and Bondeson and Miles (1996)M.
276 We are born with about five million hair follicles. For a general review of hair (and feather) specification see Oro and Scott (1998). For the role of BMPs and FGFs, Jung et al. (1998) and Noramly and Morgan (1998). Reynolds et al. (1999) carry out the trans-gender transplantation experiment.
280 The one thing that many of us. Most of the anecdotal material here comes from Segrave (1996) – a delightful social history of balding. Male pattern balding or androgenetic alopecia (109200). See Cotsarelis and Millar (2001) for a general biology of the dying hair follicle, and Kuester and Happle (1984) for a review of the genetics of the androgenetic alopecia.
282 One fact is, however, known: to go bald you need testosterone. See Aristotle Historia animalium in Collected works pp.983–4. Hamilton (1942) recounts the experiments with testosterone. Knussmann et al. (1992) discuss the relationship between testosterone levels, virility and balding.
283 Is there any hope for the bald? Trotter (1928) discusses the relationship between hair growth and shaving. Sato et al. (1999) and Callahan and Oro (2001) discuss the role of sonic hedgehog in rejuvenating hair follicles; Huelsken et al. (2001) discuss (?-catenin.
285 One can still, occasionally. The portraits of the Ambras family were first described in the modern scientific literature by the physiologist C. Th. Siebold (1878). He proposed that they were atavistic, a claim echoed by Brandt (1897), who points out that the Burmese family have the same disorder. Both men recognised that the surplus hair in the two families was lanugo (Siebold explicitly compares Petrus Gonsalvus’s hair to that of a foetal orangutan), but suppose that lanugo is more ‘primitive’ – a conflation between phylogeny and ontogeny that is typical of German workers of the time, who were deeply influenced by Haeckel. Felgenhauer (1969) gives a summary of nineteenth-century views on hairy people. More recently, there has been a great deal of debate about just how many surplus-hair syndromes there are, and who had what (see Garcia-Cruz et al. 2002 for one point of view). I argue that Petrus Gonsalvus’s and Shwe-Maong’s families both have the same condition: hypertrichosis lanuginosa (145700), the mutant gene of which may reside on chromosome 8. The hair of at least one man with this syndrome (a Russian named Adrian Jewtichjew) has been examined microscopically and seems to have been lanugo. The most famous modern pedigree of hairy people, the Gomez family of Mexico, have another, unrelated, disorder: X-linked hypertrichosis terminalis (145701); Figuera et al. (1995). See this paper and Hall (1995), recent – and perhaps reasonable – claims that this latter kind of hairiness is indeed atavistic.
286 Darwin himself knew of the Burmese hairy family. See Darwin (1871; 1981) volume 2. p.378 for his account of sexual selection and hairiness of the Burmese family; see Darwin (1859; 1968) pp.183–4 and Darwin (1882) volume 2, pp.319–21 for the homology between skin organs, the Burmese family and the ‘Hindoos of Scinde’. See Thadani (1935) for a later account of the same pedigree (the ‘Bhudas’) who have a syndrome called ectodermal dysplasia 1, anhydrotic or ED1 (305100) caused by a mutation in ectodysplasin (EDA) (Kere et al. 1996). The Mexican hairless dog’s mutation is still unknown (Schnaas 1974; Goto et al. 1987) but is probably this gene or its receptor, EDAR (224900; 604095) (Headon and Overbeek 1999; Monreal et al. 1999). The scaleless variety of Medaka has a mutation in the EDAR gene (Kondo et al. 2001). For ectodysplasin’s proposed role in establishing hair papillae see Barsh (1999). See Sharpe (2001) on the evolutionary history of the hair follicle.
288 The use of a single molecule in the making. For hens’ teeth see the classic experiments by Kollar and Fisher (1980), a commentary by Gould (1983) pp.177–86, and recent experiments showing that chicken mandibles are BMP4-defective (Chen et al. 2000).
289 Perhaps it is also the retrieval of an ancient signalling system. Nipples, supernumerary or polymastia (163700). For a review see Cockayne (1933) pp.341–5; Japanese polymastia, Iwai (1907). I thank Alan Ashworth and Beatrice Howard for telling me about Scaramanga.
290 Breasts bring us back to Linnaeus. The ancient iconography of Artemis Ephesia is discussed by Fleischer (1984) and Linnaeus’ use of it by Gertz (1948) – for the translation of which I am indebted to Lisbet Rausing. Nosce te ipsum – the slogan that meant so much to Linnaeus is rarely attributed to Solon, but rather (as in Plato) to the seven wise men of Protagorous who wrote it on the temple of Apollo at Delphi. The Oxford dictionary of quotations gives its source as ‘Anonymous’.
CHAPTER IX: THE SOBER LIFE
297 Huntington disease is one of the nastier. Huntington disease, also Huntington’s Chorea or HD (143100), is caused by dominant mutations in the huntingtin gene. Rubinsztein (2002) reviews the molecular basis of the pathology; Bruyn and Went (1986) review the history and spread of the disease.
298 How can so lethal a disorder? See Haldane (1941) pp.192–4.
300 Were it not for ageing’s pervasive effects. Ricklefs and Finch (1995) give estimates of longevity in the absence of ageing.
302 But it was another British scientist. See Medawar (1952) and Williams (1957) for the seminal papers on the evolutionary theory of ageing. Rose (1991) gives an incisive historical review. Albin (1988) discusses the fecundity of women with Huntington’s based on data collected by Reed and Neel (1959).
304 In his declining years, flush with cash and fame. Alexander Graham Bell (1918) analyses the Hyde family; Quance (1977) discusses Bell’s interests in the genetics of longevity.
306 In the 1980s the evolutionary account of ageing. See Rose (1984) for the original experiment; Rose (1991) for a review; and Sgrò and Partridge (1999)for a more detailed analysis of a similar experiment.
308 Since Aristotle. Aristotle On length and shortness of life in Complete Works volume 1 p.743. See Diamond (1982) for the cost of reproduction in marsupial mice and Westendorp and Kirk wood (1998) for the cost of reproduction in British aristocrats. See Leroi (2001) for a sceptical treatment of cost of reproduction data.
309 Is there a recipe for long life? See Cornaro (1550,1903) for a translation of the Vita sobria, and Gruman (1966) for a review of Corna
ro’s thought and its influence.
311 The worst of it is that there is an element of truth. See Finch (1990) pp.506–37 for a review of the earlier literature on caloric restriction; ibid. pp.20–1 for mortality rates of the Dutch during the Hongerwinter. See Holliday (1989) and Chapman and Partridge (1996) on reproductive costs and caloric restriction. Several experiments in flies and mice have been done to look at the effects of caloric restriction on ‘whole genome expression profiles’. The best is a study on flies (Pletcher et al. 2002); the mouse studies (Lee et al. 1999) are more difficult to interpret.
313 We term sleep a death. See Beckman and Ames (1998) and Ames et al. (1993) for a review of the free radical theory of ageing. See Rose (1991) for SOD in gerontocratic flies. Parkes et al. (1998) for overexpression of superoxide dismutase in Drosophila motorneurons; Finch and Ruvkun (2001) for a general review of SOD and ageing.
316 Our genomes contain three genes. Familial amyotrophic lateral sclerosis or ALS1 (105400) is caused by dominant mutations in Cu/Zn superoxide dismutase or SOD1 (147450) (Rosen et al. 1993). Deleting this gene in mice seems to have little obvious phenotypic effect, although longevity does not seem to have been examined (Reaume et al. 1996). For the experiments excluding free radicals and hydrogen peroxide as a cause of ALS see Subramaniam et al. (2002); for a review, Orr (2002). For a more general discussion on the causes of ALS see Newbery and Abbott (2002). For the role of SOD1 in Down’s syndrome see Epstein et al. (1987) and Reeves et al. (2001).
319 Wrinkling is a manifestation. Werner’s syndrome (277700) caused by recessive mutations in RECQL2 (also known as WRN) helicase (604611) (Yu et al. 1989) reviewed by Martin and Oshima (2000).
319 As we age. For two reviews of the proposed role of cellular senesence (or Hayflick’s limit) in ageing see Rose (1991) pp.126–36 and Shay and Wright (2000). Bodnar et al. (1997) show that overexpression of telomerase in human cell lines confers cellular immortality. There are some reports that the neuronal cells of mice do not undergo cellular senesence in vitro (Tang et al. 2001; Mathon et al. 2001). There are also strong suggestions that the proliferation of mouse cells in vitro is not telomere limited (Shay and Wright 2000).
321 Mice, it seems, can get by without telomerase. See Blasco et al. (1997), Lee et al. (1998) and Rudolph et al. (1999) for telomerase-deficient mice. One worry about these results is that laboratory mice seem to have much longer telomeres than wild mice (Weinstein and Ciszek, 2002).
322 One way to prove the point would be to clone a human. The original report on cloning Dolly was Wilmut et al. (1997). She died on 14 February 2003. Shiels et al. (1999) reported Dolly’s short telomeres. Cloned cattle appear to have perfectly normal, indeed rather long, telomeres (Lanza et al. 2000; Betts et al. 2001). There is a controversy about the healthiness of cloned animals (Cibelli et al. 2002; Wilmut, 2002). Six generations of mice have been cloned with no sign of rapid ageing – but then, they do seem to have very long telomeres.
323 Telomerase-mutant humans. Hutchinson-Gilford syndrome (progeria)(176670) is caused by a mutation in the gene encoding Lamin A and C.
323 In the last ten years there has been a revolution. See Kenyon et al. (1993) for a pioneering paper in C. elegans ageing studies, and Leroi (2001), Finch and Ruvkun (2001) and Partridge and Gems (2002) for recent reviews.
326 One of the first longevity genes to be identified. Alzheimer’s disease (104300). Late onset (AD2) is associated with particular polymorphisms in the apolipoprotein E gene (107741). For the relative risk of the ?4 allele see Corder et al. (1993); for its rarity in French centenarians see Schächter et al. (1994) and Charlesworth (1996).
327 All this seems to matter less if you are black. For the worldwide distribution of APOE alleles and discussion of relative risk of Alzheimer’s among ethnic groups see Fullerton et al. (2000). There are two ideas why Africans may not feel the deleterious effects of the ?4 allele. First, haplotype analysis shows that their ?4 alleles are somewhat different from those in European populations. Perhaps it simply lacks the pathogenic effect. Second, perhaps it has exactly the same effect, but Africans have, at high frequency, a variant at another locus that protects them against ?4. There is no reason to favour one idea over the other. For African APOE allele frequencies see Zekraoui et al. (1997).
327 In Europeans, at least, the genetics of Alzheimer’s provide. The early onset Alzheimer’s genes are: AD1, ?APP (104760); AD3, Presenilin 1 (104311) and AD4, Presenilin 2 (600759) (Charlesworth 1996).
327 These kinds of findings are only the beginning. Heijmans et al. (2000) review the state of the centenarian gene hunt.
329 In 1994 a remarkable thing happened. Much of the discussion on late-life mortality trends is based on Wilmoth (2000) and Wilmoth et al. (2000).
CHAPTER X: ANTHROPOMETAMORPHOSIS
335 The authors of books. Steve Jones, in the concluding chapter of his The language of the genes (1993) HarperCollins, London gives a classic Utopian account of humanity’s future. Mark Ridley, in the concluding chapter of his Mendel’s demon (2000) Weidenfeld and Nicolson, London suggests the wacky, but interesting, idea that we might evolve huge genomes and fantastically complex life-cycles. For the ethical views of some of the less inhibited scientists see the writings of Richard Dawkins and the late William Hamilton; for the opposition see the New York Review of Books (New York) and the Sunday Times (London).
337 Race has long been under siege. Steve Jones gives a good, if dated, account of these issues in The language of the genes. More recently, see Barbujani et al. (1997) and Rosenburg et al. (2002) for studies based on microsatellite loci; and Stephens et al. (2001) for single nucleotide polymorphisms.
339 The variants are known as AIMS. For an account of the search for AIMS see Collins-Schramm et al. (2002) and Shriver et al. (2003). For an account of the molecular genetics of FY (also known as Duffy) see Li et al (1997).
340 Skull measuring has a long history. See Bindman (2002) pp.201–21 for Camper on skull measurement (from which the quotes as well).
340 Sadly, Camper’s iconography. See Gould (1981) for the classic debunking work on craniometry and IQ. See Lahr (1996), Hanihara (2002) and Hennessy and Stringer (2002) for recent major craniometric studies, all of which build on the work of Bill Howells.
341 Human skulls are wonderfully diverse. See Lahr (1996) for an authoritative treatment of recent human skull diversity. The relative prognathism of Eskimos and Australian Aborigines is calculated from Hanihara (2002) Table 3.
342 My claim that we will soon be able. Boas published several studies on his immigrant data set, the most important of which was Boas (1912). The Rose quote is from Boyd (1955) p.299. Two recent papers, Sparks and Jantz (2002) and Gravlee et al. (2003), have reanalysed Boas’s data. The analysis done by each is somewhat different and they draw somewhat different conclusions. Sparks and Jantz (2002), however, do the critical analysis of variance – with ancestry, birthplace and their interaction as the effects. They show that there is a significant effect of birthplace and – just as one would expect from Boas’s hypothesis – a strong interaction effect. Contrary to Boas, however, the plasticity is small compared to the persistence of ancestral effects and the interactions are not of the sort that would necessarily cause skull shape to converge. They do not accuse Boas of fraud, but one cannot help but suspect that he presented those results that favoured his hypothesis and ignored those that did not. Gould (1981) p.108 cites Boas with approval.
347 They are only the latest casualties. See notes to Chapter VI for the history of the negritos as well as the various essays in McEwan et al. (1997) for a history of the Selk’nam and their legend and their fate.
348 ‘Beauty,’ says the philosopher. See Scarry (2000) p.4 for beauty and the impulse to reproduce. See Plato, The symposium (trans. W. Hamilton. 1951. Penguin Books, Harmondsworth, UK) p.87 for the same. See Darwin (1871, 1981) Vol. 2 p.92 for the Argus pheasant. See Bindman (2002) for a survey of eighteenth-century aesthetic theory with respect to race. See Darwin
(1871, 1981) V0I.2 pp.342–54 on the particularity of beauty.
351 The universality of beauty’s standard. See Thornhill and Gangestad (1999) for a survey of the recent literature on facial attractiveness. See Perrett et al. (1994) for a classical study on the perception of female beauty. What Brazilians say is recorded (with delight) by the late William Hamilton in The narrow roads of gene land (2002, Oxford University Press, Oxford) Vol. 2 p.677. Many of the ideas about the meaning of beauty expressed in this chapter can be traced to Hamilton’s writings.
353 The effects of poor childhood nutrition. For the genetics of the face see Winter (1996). For spontaneous abortion as an adaptation to eliminate defective embryos see Forbes (1997).
354 Mutation is a game of chance. See Crow (2000) for the number of deleterious mutations and a model of truncation selection.
356 Beauty, Stendhal says. Stendhal, De l’amour (Folio, Paris) p.59.
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