Let’s celebrate human genetic diversity
Bruce Lahn and Lanny Ebenstein
Nature, 8 October 2009
Science is finding evidence of genetic diversity among groups of people as well as among individuals. This discovery should be embraced, not feared, say Bruce T. Lahn and Lanny Ebenstein.
A growing body of data is revealing the nature of human genetic diversity at increasingly finer resolution. It is now recognized that despite the high degree of genetic similarities that bind humanity together as a species, considerable diversity exists at both individual and group levels (see box, page 728). The biological significance of these variations remains to be explored fully. But enough evidence has come to the fore to warrant the question: what if scientific data ultimately demonstrate that genetically based biological variation exists at non-trivial levels not only among individuals but also among groups? In our view, the scientific community and society at large are ill-prepared for such a possibility. We need a moral response to this question that is robust irrespective of what research uncovers about human diversity. Here, we argue for the moral position that genetic diversity, from within or among groups, should be embraced and celebrated as one of humanity’s chief assets.
The current moral position is a sort of ‘biological egalitarianism’. This dominant position emerged in recent decades largely to correct grave historical injustices, including genocide, that were committed with the support of pseudoscientific understandings of group diversity. The racial-hygiene theory promoted by German geneticists Fritz Lenz, Eugene Fischer and others during the Nazi era is one notorious example of such pseudoscience. Biological egalitarianism is the view that no or almost no meaningful genetically based biological differences exist among human groups, with the exception of a few superficial traits such as skin colour. Proponents of this view seem to hope that, by promoting biological sameness, discrimination against groups or individuals will become groundless.
We believe that this position, although well intentioned, is illogical and even dangerous, as it implies that if significant group diversity were established, discrimination might thereby be justified. We reject this position. Equality of opportunity and respect for human dignity should be humankind’s common aspirations, notwithstanding human differences no matter how big or small. We also think that biological egalitarianism may not remain viable in light of the growing body of empirical data.
Many people may acknowledge the possibility of genetic diversity at the group level, but see it as a threat to social cohesion. Some scholars have even called for a halt to research into the topic or sensitive aspects of it, because of potential misuse of the information. Others will ask: if information on group diversity can be misused, why not just focus on individual differences and ignore any group variation? We strongly affirm that society must guard vigilantly against any misuse of genetic information, but we also believe that the best defence is to take a positive attitude towards diversity, including that at the group level. We argue for our position from two perspectives: first, that the understanding of group diversity can benefit research and medicine, and second, that human genetic diversity as a whole, including group diversity, greatly enriches our species.
Box 2. Emerging understanding of human genetic diversity
Genetic diversity is the differences in DNA sequence among members of a species. It is present in all species owing to the interplay of mutation, genetic drift, selection and population structure. When a species is reproductively isolated into multiple groups by geography or other means, the groups differentiate over time in their average genetic make-up.
Anatomically modern humans first appeared in eastern Africa about 200,000 years ago. Some members migrated out of Africa by 50,000 years ago to populate Asia, Australia, Europe and eventually the Americas. During this period, geographic barriers separated humanity into several major groups, largely along continental lines, which greatly reduced gene flow among them. Geographic and cultural barriers also existed within major groups, although to lesser degrees.
This history of human demography, along with selection, has resulted in complex patterns of genetic diversity. The basic unit of this diversity is polymorphisms — specific sites in the genome that exist in multiple variant forms (or alleles). Many polymorphisms involve just one or a few nucleotides, but some may involve large segments of genetic material. The presence of polymorphisms leads to genetic diversity at the individual level such that no two people’s DNA is the same, except identical twins. The alleles of some polymorphisms are also found in significantly different frequencies among geographic groups. An extreme example is the pigmentation gene SLC24A5. An allele of SLC24A5 that contributes to light pigmentation is present in almost all Europeans but is nearly absent in east Asians and Africans.
Given these geographically differentiated polymorphisms, it is possible to group humans on the basis of their genetic make-up. Such grouping largely confirms historical separation of global populations by geography. Indeed, a person’s major geographic group identity can be assigned with near certaintly on the basis of his or her DNA alone (now an accepted practice in forensics). There is growing evidence that some of the geographically differentiated polymorphisms are functional, meaning that they can lead to different biological outcomes (just how many is the subject of ongoing research). These polymorphisms can affect traits such as pigmentation, dietary adaptation and pathogen resistance (where evidence is rather convincing), and metabolism, physical development and brain biology (where evidence is more preliminary).
For most biological traits, genetically based differentiation among groups is probably negligible compared with the variation within the group. For other traits, such as pigmentation and lactose intolerance, differences among groups are so substantial that the trait displays an inter-group difference that is non-trivial compared with the variance within groups, and the extreme end of a trait may be significantly over-represented in a group.
Several studies have shown that many genes in the human genome may have undergone recent episodes of positive selection — that is, selection for advantageous biological traits. This is contrary to the position advocated by some scholars that humans effectively stopped evolving 50,000–40,000 years ago. In general, positive selection can increase the prevalence of functional polymorphisms and create geographic differentiation of allele frequencies.
This paper was even written up in the New York Times (with obligatory “opposing view” that doesn’t amount to much).
Categorization of humans in biomedical research: genes, race and disease
Neil Risch, Esteban Burchard, Elad Ziv, and Hua Tang
Genome Biology, 2002
With this as background, it is not surprising that numerous human population genetic studies have come to the identical conclusion – that genetic differentiation is greatest when defined on a continental basis. The results are the same irrespective of the type of genetic markers employed, be they classical systems , restriction fragment length polymorphisms (RFLPs) , microsatellites [7,8,9,10,11], or single nucleotide polymorphisms (SNPs) . For example, studying 14 indigenous populations from 5 continents with 30 microsatellite loci, Bowcock et al.  observed that the 14 populations clustered into the five continental groups, as depicted in Figure 1. The African branch included three sub-Saharan populations, CAR pygmies, Zaire pygmies, and the Lisongo; the Caucasian branch included Northern Europeans and Northern Italians; the Pacific Islander branch included Melanesians, New Guineans and Australians; the East Asian branch included Chinese, Japanese and Cambodians; and the Native American branch included Mayans from Mexico and the Surui and Karitiana from the Amazon basin. The identical diagram has since been derived by others, using a similar or greater number of microsatellite markers and individuals [8,9]. More recently, a survey of 3,899 SNPs in 313 genes based on US populations (Caucasians, African-Americans, Asians and Hispanics) once again provided distinct and non-overlapping clustering of the Caucasian, African-American and Asian samples : “The results confirmed the integrity of the self-described ancestry of these individuals”. Hispanics, who represent a recently admixed group between Native American, Caucasian and African, did not form a distinct subgroup, but clustered variously with the other groups. A previous cluster analysis based on a much smaller number of SNPs led to a similar conclusion: “A tree relating 144 individuals from 12 human groups of Africa, Asia, Europe and Oceania, inferred from an average of 75 DNA polymorphisms/individual, is remarkable in that most individuals cluster with other members of their regional group” . Effectively, these population genetic studies have recapitulated the classical definition of races based on continental ancestry – namely African, Caucasian (Europe and Middle East), Asian, Pacific Islander (for example, Australian, New Guinean and Melanesian), and Native American.
Populations that exist at the boundaries of these continental divisions are sometimes the most difficult to categorize simply. For example, east African groups, such as Ethiopians and Somalis, have great genetic resemblance to Caucasians and are clearly intermediate between sub-Saharan Africans and Caucasians . The existence of such intermediate groups should not, however, overshadow the fact that the greatest genetic structure that exists in the human population occurs at the racial level.
Most recently, Wilson et al.  studied 354 individuals from 8 populations deriving from Africa (Bantus, Afro-Caribbeans and Ethiopians), Europe/Mideast (Norwegians, Ashkenazi Jews and Armenians), Asia (Chinese) and Pacific Islands (Papua New Guineans). Their study was based on cluster analysis using 39 microsatellite loci. Consistent with previous studies, they obtained evidence of four clusters representing the major continental (racial) divisions described above as African, Caucasian, Asian, and Pacific Islander. The one population in their analysis that was seemingly not clearly classified on continental grounds was the Ethiopians, who clustered more into the Caucasian group. But it is known that African populations with close contact with Middle East populations, including Ethiopians and North Africans, have had significant admixture from Middle Eastern (Caucasian) groups, and are thus more closely related to Caucasians . Furthermore, the analysis by Wilson et al.  did not detect subgroups within the four major racial clusters (for example, it did not separate the Norwegians, Ashkenazi Jews and Armenians among the Caucasian cluster), despite known genetic differences among them. The reason is clearly that these differences are not as great as those between races and are insufficient, with the amount of data provided, to distinguish these subgroups.
Are racial differences merely cosmetic?
Two arguments against racial categorization as defined above are firstly that race has no biological basis [1,3], and secondly that there are racial differences but they are merely cosmetic, reflecting superficial characteristics such as skin color and facial features that involve a very small number of genetic loci that were selected historically; these superficial differences do not reflect any additional genetic distinctiveness . A response to the first of these points depends on the definition of ‘biological’. If biological is defined as genetic then, as detailed above, a decade or more of population genetics research has documented genetic, and therefore biological, differentiation among the races. This conclusion was most recently reinforced by the analysis of Wilson et al. . If biological is defined by susceptibility to, and natural history of, a chronic disease, then again numerous studies over past decades have documented biological differences among the races. In this context, it is difficult to imagine that such differences are not meaningful. Indeed, it is difficult to conceive of a definition of ‘biological’ that does not lead to racial differentiation, except perhaps one as extreme as speciation.
A forceful presentation of the second point – that racial differences are merely cosmetic – was given recently in an editorial in the New England Journal of Medicine : “Such research mistakenly assumes an inherent biological difference between black-skinned and white-skinned people. It falls into error by attributing a complex physiological or clinical phenomenon to arbitrary aspects of external appearance. It is implausible that the few genes that account for such outward characteristics could be meaningfully linked to multigenic diseases such as diabetes mellitus or to the intricacies of the therapeutic effect of a drug.” The logical flaw in this argument is the assumption that the blacks and whites in the referenced study differ only in skin pigment. Racial categorizations have never been based on skin pigment, but on indigenous continent of origin. For example, none of the population genetic studies cited above, including the study of Wilson et al. , used skin pigment of the study subjects, or genetic loci related to skin pigment, as predictive variables. Yet the various racial groups were easily distinguishable on the basis of even a modest number of random genetic markers; furthermore, categorization is extremely resistant to variation according to the type of markers used (for example, RFLPs, microsatellites or SNPs).
Genetic differentiation among the races has also led to some variation in pigmentation across races, but considerable variation within races remains, and there is substantial overlap for this feature. For example, it would be difficult to distinguish most Caucasians and Asians on the basis of skin pigment alone, yet they are easily distinguished by genetic markers. The author of the above statement  is in error to assume that the only genetic differences between races, which may differ on average in pigmentation, are for the genes that determine pigmentation.
Anti-racist PC agendas and the American Anthropological Association’s recent confirmation of the unity of the human species have led to the belief that race is a socio-political invention that promotes racism. An ironic accusation since the denial of the science behind race is what’s politically motivated. Forensic anthropologist and professor of anthropology George W. Gill, whose assessments are supported by modern genetics, explains.
“First, I have found that forensic anthropologists attain a high degree of accuracy in determining geographic racial affinities (white, black, American Indian, etc.) by utilizing both new and traditional methods of bone analysis. Many well-conducted studies were reported in the late 1980s and 1990s that test methods objectively for percentage of correct placement. Numerous individual methods involving midfacial measurements, femur traits, and so on are over 80 percent accurate alone, and in combination produce very high levels of accuracy. No forensic anthropologist would make a racial assessment based upon just one of these methods, but in combination they can make very reliable assessments, just as in determining sex or age. In other words, multiple criteria are the key to success in all of these determinations.
“The ‘reality of race’ therefore depends more on the definition of reality than on the definition of race. If we choose to accept the system of racial taxonomy that physical anthropologists have traditionally established—major races: black, white, etc.—then one can classify human skeletons within it just as well as one can living humans. The bony traits of the nose, mouth, femur, and cranium are just as revealing to a good osteologist as skin color, hair form, nose form, and lips to the perceptive observer of living humanity. I have been able to prove to myself over the years, in actual legal cases, that I am more accurate at assessing race from skeletal remains than from looking at living people standing before me. So those of us in forensic anthropology know that the skeleton reflects race, whether ‘real’ or not, just as well if not better than superficial soft tissue does. The idea that race is ‘only skin deep’ is simply not true, as any experienced forensic anthropologist will affirm.
“Morphological characteristics…like skin color, hair form, bone traits, eyes, and lips tend to follow geographic boundaries coinciding often with climatic zones. This is not surprising since the selective forces of climate are probably the primary forces of nature that have shaped human races with regard not only to skin color and hair form but also the underlying bony structures of the nose, cheekbones, etc. (For example, more prominent noses humidify air better.) As far as we know, blood-factor frequencies [used to deny race] are not shaped by these same climatic factors.
“Those who believe that the concept of race is valid do not discredit the notion of clines, however. Yet those with the clinal perspective who believe that races are not real do try to discredit the evidence of skeletal biology. Why this bias from the ‘race denial’ faction? This bias seems to stem largely from socio-political motivation and not science at all. For the time being at least, the people in ‘race denial’ are in ‘reality denial’ as well. Their motivation (a positive one) is that they have come to believe that the race concept is socially dangerous. In other words, they have convinced themselves that race promotes racism. Therefore, they have pushed the politically correct agenda that human races are not biologically real, no matter what the evidence.”
“A detailed genetic analysis of more than a thousand human subjects clusters them into five groups corresponding to major geographical regions. This new study shows that self-reported ancestry is a good predictor of one’s genetic make-up.
“The novelty of the recent work of Rosenberg et al.  is precisely that they have checked the validity of the population-sampling approach and tried to define the genetic structure of the human population without using a priori information on the geographic origin of the individuals. For that purpose, they used the structure program, which attempts to find, for each individual, the proportion of its genome that comes from a given ‘population’, whose unknown genetic constitution is estimated in the same process. This procedure is performed successively with the assumption of an increasing number of ‘populations’ or clusters (K): K = 2, 3, 4 and so on.
“Rosenberg et al. applied this procedure to 1056 individuals analyzed for 377 autosomal short tandem repeat (STR) loci. This data set is the first outcome of the analysis of a cell-line panel of 52 worldwide populations…. The results obtained…are quite remarkable. For K = 2 case, where it is assumed that there are two clusters, a contrast is found between individuals from sub-Saharan Africa and native Amerindians. Individuals from other regions seem to harbor various proportions of ‘African’ genes, with a tendency to a dilution of these genes with distance from Africa.
“Assuming that three populations are present (K = 3) leads to a split of individuals found in sub-Saharan Africa from those found in Europe, North-Africa, the Middle East and Pakistan (Figure 1, barrier 2). With K = 4, a cluster of Asiatic and Oceanian individuals separates from Amerindians (Figure 1, barrier 3). With K = 5, an Oceanian cluster appears (Figure 1, barrier 4), and we are left with the pleasant picture of a world divided into genetic clusters that closely correspond to five geographic regions: sub-Saharan Africa, East Asia, Oceania, the Americas and the rest, comprising Europe, North Africa and West Asia. … It thus seems that these five groups do correspond to major subdivisions of the human population.”
* * *
Here’s the chart of inferred population structure from a revised version of Rosenberg’s study, in which the data set was increased from 377 polymorphisms to 993:
RACES OF MAN
A brief overview of human races and their geographical distribution, with illustrative plates from Carleton S. Coon’s The Origin of Races.
Caucasoid: Europe, West Asia and North Africa.
Mongoloid: East Asia, Oceania, the Arctic and the Americas.
Negroid: Sub-Saharan Africa.
Capoid: Southern Africa.
Australoid: Australia and Melanesia.