Skip to comments.On Human Diversity: Why has the genetics community discarded so many phenotypes?
Posted on 10/25/2005 8:03:25 PM PDT by Pharmboy
The physical phenotypic differences between this
Sudanese skull (right) and this European skull (left)
are apparent. (From J.L.A. de Quatrefages, E.T.
Hamy, Crania ethnica: les Cranes des races
humaines, Baillere et fils: Paris, 1882.)
Henry Flower became director of the British Museum of Natural History in 1884, and promptly set about rearranging exhibits. He set a display of human skulls to show their diversity of shape across the globe. A century later, the skulls had gone, and in their place was a large photograph of soccer fans standing in their terraces bearing the legend: "We are all members of a single species, Homo sapiens. But we are not identical." In 2004 even this went, and so it is that the world's greatest natural history museum has nothing to say to the public about the nature and extent of human biological diversity.
Of course, The Natural History Museum, as the British Museum of Natural History is now known, is not the only institution to relegate such demonstrations to the basement. After the 1960s, physical anthropologists, struggling to bury the idea of race, buried phenotypes as well sometimes literally so, as human remains have been reinterred by aboriginal claimants. They turned, instead, to comfortably neutral genetic markers to unravel the highways and byways of human history. This magnificent enterprise has charted our species' path out of Africa using successive generations of markers: blood type, allozyme, mitochondrial DNA, the Y chromosome, and nuclear single nucleotide polymorphisms (SNPs). But is it enough? I would argue not. I would argue that it is time to resurrect the study of human phenotypic diversity.
ON HUMAN DIVERSITY
It is one of the oddities of human genetics that, for all we know about the basis of inherited disease, we know very little about the causes of normal physical variety. Online Mendelian Inheritance in Man lists the molecular causes of about 1,800 inherited diseases. Yet we know very little about why the Dinka of the Sudan are so tall and African pygmies so small, why the Yakut of Siberia have such high basal metabolic rates, why the Sea Gypsies of Indonesia can see so well underwater, why the Yoruba of Nigeria have so many dizygotic twins, or even why the colors of our skin, eyes, and hair vary across the globe.
A NOSE FOR VARIETY:
The distribution of nasal prominence (nasodacryl subtense) in African and
European skulls. The 317 European skulls are Hungarian, Norwegian, and Austrian;
the 283 Sub-Sahara African skulls are Dogon, Zulu, and Teita. Data from Howells
Three reasons, I believe, underlie the neglect of these traits. First, they are associated with racial biology, now unfashionable. Second, they are often of little relevance to human health. And third, they are probably genetically complex traits, influenced by multiple loci that interact with each other, and sometimes with the environment, in complex ways.
A new approach to analyzing quantitative traits, called admixture mapping, seems ideal for studying normal human variety. The principle is simple. Suppose that two isolated populations differ in some heritable attribute. Now suppose that individuals from these populations meet and mate so that, after many generations, a thoroughly admixed population of descendants exists. Each descendant will have some unique mix of the ancestral genomes, and the attributes of each will depend on what that mix is. By studying many descendants it is then possible, in principle, to map the gene (or genes) responsible for the attribute by showing that it appears only in those who have inherited a given genomic region from one, but not the other, of the ancestral populations.
David Reich's group at Harvard Medical School provided a set of ancestral genetic markers for African and European genomes.1 Screening through the hundreds of thousands of biallelic SNPs in the genomic databases, they identified 2,154 that showed substantial (>30%) differences in allele frequency between West Africans and Europeans. Moreover, software to cope with noncausal linkages that population stratification throws up has now been developed.2,3
Many think that admixture mapping will be a valuable adjunct to more traditional methods of mapping complex traits. In one promising test run, Neil Risch's group at Stanford University showed that African Americans with hypertension have a higher probability of African ancestry for two genomic regions 6q24 and 21q21 than their nonhypertensive relatives.4 If this result is replicated it will no longer be possible to claim that the racial disparity in the rates of this disease is due entirely to socioeconomic factors or even the direct effect of racism itself.
Armand M. Leroi
For admixture mapping to work, ancestral populations must differ substantially in the frequencies of disease-causing alleles. It's unclear how often this is true. Yet even if the technique isn't ultimately useful for hunting disease genes, there is another application for which it could have been tailor made: the study of normal racial variety. Recently, Mark Shriver's group at Pennsylvania State University used a form of admixture mapping in African Americans to show that two genes, TYR and OCA2, were linked to skin colors. It was the first hint of the genes underlying the diversity that is at once so commonplace and so mysterious. Even more delightful, the two genes identified were already known to be involved in pigmentation: Strong loss-of-function mutations in each cause albinism.
GETTING PAST THE SKULLDUGGERY
What might be studied next? Although a controversial topic, skulls seem an obvious choice. Studies by the American anthropologist Franz Boas nearly a hundred years ago convincingly suggested that skull shape was not heritable. He found that differences in the skulls of European immigrants arriving at Ellis Island were less evident in their American-born children. But recent reanalysis of Boas' data show that ancestral differences in skull shape were hardly influenced by environment.6
Skulls are easy to obtain, easy to measure, and vary richly in shape. In a classic study, the doyen of modern craniometry, William Howells, measured (among others) 317 European skulls and 283 Sub-Saharan African skulls in 81 different ways.7 If his data are representative they imply, for example, that European noses are, on average, more prominent than African noses, but many Africans and Europeans do not differ in this trait. Other well documented differences: European noses are set higher on the face, and are longer and narrower than African noses. Europeans have higher cheekbones, wider crania and more prominent foreheads than Africans. Europeans also have slightly longer crania than Africans, but the difference is mostly one of shape, Europeans being more brachycephalic than Africans. African jaws protrude more from the face than do European jaws (the former are more prognathic). Africans have wider orbits and wider interorbital spaces than Europeans.
These kinds of differences are simply those that we see when we look at the faces around us. They are not large, much less absolute, yet power calculations suggest that they should be amenable to admixture mapping (Leroi unpublished data). And we can make some guesses as to what sort of genes might underlie such variety. Many inherited disorders affect the face and skull, and the mutations responsible for many of them are known.8,9 For example, if one were studying interorbital distance (the distance between the eyes), 7q36 would be a good place to look, for that is the location of the gene encoding Sonic Hedgehog, which developmental and clinical geneticists have shown controls the width of our faces.
Of course, identifying the genes responsible for normal human variety is only the first step. There is a long tradition of speculation about whether racial differences in appearance are due to drift, natural selection, or even sexual selection. Such hypotheses can be tested by searching for the traces of selection in the genes that give us our looks. That, however, is for the future. And enthusiasm must be tempered by the recognition that such studies come with their own ethical and sociological problems. Medical geneticists rightly worry that misinterpretations might promote racial divisions or inflame the sensitivities of historically disenfranchised minority groups. Such concerns become even more acute when studying traits of no medical relevance and which have, as skull dimensions do, the taint of 19th-century racist science. My own view, or rather, hope, is that such concerns can be allayed given sufficient care, sensitivity, and candor on the part of researchers. Humans are, after all, the most phenotypically diverse species of mammal, perhaps animal, on earth. It would be a shame were we never to know why.
Armand M. Leroi is a reader in evolutionary developmental biology at Imperial College London. He wrote Mutants: On Genetic Variety and the Human Body, and the Channel 4/Discovery UK's series Human Mutants.
He can be contacted at firstname.lastname@example.org.
1. MW Smith et al, "A high-density admixture map for disease gene discovery in African Americans," Am J Hum Genet 2004, 74: 1001-13. [PubMed Abstract][Publisher Full Text][PubMed Central Full Text]
2. CJ Hoggart et al, "Design and analysis of admixture mapping studies," Am J Hum Genet 2004, 74: 965-78. [PubMed Abstract][Publisher Full Text][PubMed Central Full Text]
3. N Patterson et al, "Methods for high-density admixture mapping of disease genes," Am J Hum Genet 2004, 74: 979-1000. [PubMed Abstract][Publisher Full Text][PubMed Central Full Text]
4. X Zhu et al, "Admixture mapping for hypertension loci with genome-scan markers," Nat Genet 2005, 37: 177-81. [PubMed Abstract][Publisher Full Text]
5. MD Shriver et al, "Skin pigmentation, biogeographical ancestry and admixture mapping," Hum Genet 2003, 112: 387-99. [PubMed Abstract][Publisher Full Text]
6. CS Sparks, RL Jantz "A reassessment of human cranial plasticity. Boas revisited," Proc Natl Acad Sci 2002, 99: 14636-9. [PubMed Abstract][Publisher Full Text][PubMed Central Full Text]
7. WW Howells Skull Shapes and the Map, Cambridge: Mass., Peabody Museum of Archaeology and Ethnology 1989.
8. MM Cohen "Malformations of the craniofacial region: Evolutionary, embryonic, genetic, and clinical perspectives," Am J Hum Gen 2002, 115: 245-68.
9. AM Leroi Mutants: On Genetic Variety and the Human Body, Viking: New York 2003.
I'll be a son of a gun. Sea Gypsies.
Leroi shall be burned as a heretic by the Harvard, excuse me, the Spanish Inquistion.
Figured you might want to see this one...
It can be done - chemistry was eventually extracted from and divorced from alchemy, astronomy from astrology. But what to keep, and what to discard will be a decision process that will be hampered constantly by vestiges of racism and accusations of its further promotion. I wish the fellow luck.
Great comment. And, the Nazis set back genetic research a looooong time.
Leroi is generally respected by other scientists. They do point out (and quite correctly I might add) that his work is used over and over again by racists who have very little understanding of his work, which is rather unfortunate.
Thanks for the info, I think I suffer from professional myopia, you see when you say, phenotypes, I think immunohematology.
The early efforts to analyze crania met with little success as the computing power to crunch the numbers did not yet exist.
In more recent times, the computing power is there, but the study of modern cranial morphology has largely been passed over in favor of non-metric traits and, more recently, DNA, etc.
Still, I think there are still a few good studies left to do on metric cranial morphology.
... for that is the location of the gene encoding Sonic Hedgehog...
ya gotta be kiddin' me
Not in the slightest. It is a gene named by fruit fly geneticists and they are a bunch of WILD AND CRAZY GUYS! They have a gene called Decaplexaplegic, and when they found a gene that regulates that gene they named it Mothers against Decaplexaplegic. They also named a gene INDY for the Monty Python gag "I'm not dead yet", it is a gene that protects the cell from programmed cell death.
And the moral of the story: science always loses whenever politicians start dictating what its findings should be. This is even worse when introducing "political correctness" into the mix.
Nope...don't know Sailer. A woman that I work with who is a scientist sent it to me...thought the freepers would like to see it.
Disagree. And, that is part of what Leroi talks about--there is a diversity of proteins in the races--this goes beyond skin deep.
Indeed ... and brains.
Some Leroi facts:
He's a Brit resident, born in NZ of Dutch parents (his father was a diplomat).
Now holds the position previously held by "Darwin's Bulldog" Thomas Huxley.
His book Mutants awarded The Guardian's Book of the Year reward in 2004 (2003?).
His most important (wink) paper found here
... that paper discussed here ...
Interesting...thanks for the info.
Classical racial traits (skin color, hair color, nose form, etc.) are adaptations to local climates.
Genetic traits (fingerprint patterns, blood types, mtDNA, etc.) track descent.
No--you're going backwards, starting with the genes and going to the phenes. What I'm saying is that once we assign race (admittedly based on appearance and geography)--and look at protein polymorphisms or SNPs in the DNA--we find differences between groups. How they arose are likely due to multiple causes, eg., natural selection, founder effect (esp. on islands), sexual selection, neutral effetcs (Kimora) and genetic drift.
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"Race is really more about aesthetics than anything else. You look the way you do because your ancestors found that look attractive. Studying race says more about what made Great^n-grandpa hot-to-trot than it says anything about you."
Living in Japan, I've had a lot of occasion to think about that, because so many females here are bow-legged, knock-kneed, and pigeon-toed. Yours was the only explanation I could come up with for that.
Why not check the variation in skull shapes within families first?
"Classical racial traits (skin color, hair color, nose form, etc.) are adaptations to local climates."
But in historical times, blondes with nice noses have had a reproductive advantage. Among American blacks today, those with lighter skin do.
Thanks, I never knew this.
See post 2...
Your point is??
But in historical times, blondes with nice noses have had a reproductive advantage. Among American blacks today, those with lighter skin do.
My comments reflect earlier time periods, when people migrated slowly (i.e., pre-sailing ship and excluding organized warfare--Genghis Khan and the like).
That way there is plenty of time for adaptations as you go along.
"That way there is plenty of time for adaptations as you go along."
Yes, that's true. However, developments during historical times must have clouded the picture.
Sonic hedgehog from gassed drosophila ....somehow fitting! We used to pack drinking straws with them after playing with their generations and then we slid the straws under some poor soul's door after pulling the cotton puff with which we corked them.
Fair enough, but Darwinism provided the structure and focus for their racism much as Chrstianity provides a structure and focus for some racist groups in the US today.
Racist hate by Christians is no more rooted in actual Christianity than the racist hate of the skull shapers is based upon Darwin or Science.
Going back to my broader point, it was meant to explain why science is so reluctant to talk about physiological racial differences or even the entire topic of general intelligence. It's because those theories have a long history of being abused by racists to give their racism some credibility by tying it to science. The idea is that certain ideas end no place good, and I think you'll find some of those same sentiments in the opposition to evolution.
There is no "primitive on the evolutionary scale" or 'advanced on the evolutionary scale'. There is no progress in evolution, only adaptation.
I agree that one reason that people don't get into this field is due to the racist that have so thoroughly muddied the water, but there is really little utility in it OTHER than assigning skulls to one group or the other in groups that are not otherwise different in much of a relevant degree. The motive behind this is usually racist to begin with.
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