The 85% truism

How much of the genome varies within our species? The question remained unanswered in my last post. Hawks et al (2007) have recently estimated that at least 7% of our genome has changed over the last 40,000 years—a period that has seen humans move into diverse environments with different selection pressures. Yet this is a minimal estimate that excludes much variation that may or may not be due to natural selection. The real figure could be higher. Much higher.

How is this genetic variation distributed among humans? Is it evenly scattered? Or does it form geographic clusters? Intuitively, the second answer seems more correct: This variation should be very unevenly distributed if it is due to humans settling in diverse environments with different selection pressures. It should occur primarily at the transition from one ecological zone to another or from one cultural zone to another (e.g., from agriculturalists to hunter-gatherers).

Yet this is not what we see in the data. If we look at genetic markers (blood types, serum proteins, enzymes, etc.), we consistently find far more variation within human populations than between them. And this is true not only for large ‘continental’ groups but also for smaller local populations. In a landmark paper, Richard Lewontin (1972, p. 397) concluded that 85% of human genetic variation exists only between individuals and not between populations:

It is clear that our perception of relatively large differences between human races and subgroups, as compared to the variation within these groups, is indeed a biased perception and that, based on randomly chosen genetic differences, human races and populations are remarkably similar to each other, with the largest part by far of human variation being accounted for by the differences between individuals.

This finding is true. Like many findings, however, it does not necessarily mean what we think it means. This became apparent when geneticists looked at genetic markers in other animals, such as dogs:

… genetic and biochemical methods … have shown domestic dogs to be virtually identical in many respects to other members of the genus. … Greater mtDNA differences appeared within the single breeds of Doberman pinscher or poodle than between dogs and wolves. Eighteen breeds, which included dachshunds, dingoes, and Great Danes, shared a common haplotype and were no closer to wolves than poodles and bulldogs. These data make wolves resemble another breed of dog.

… there is less mtDNA difference between dogs, wolves, and coyotes than there is between the various ethnic groups of human beings, which are recognized as a single species. (Coppinger & Schneider, 1995)

One could object that humans have created dog breeds using a limited set of criteria that reflect a limited set of genes. Therefore, all other criteria, especially those not visible to the eye, should vary independently of breed. The category ‘breed’ is thus an artificial construct that human selection, and not natural selection, has imposed on canine genetic variability.

This objection is not wholly true. Many breeds, such as dingoes, originated in prehistory long before kennel clubs. More to the point, if one argues that human selection acts on a limited set of genes, the implication is that natural selection acts on the entire genome. It doesn’t. Natural selection also acts on a limited set of genes, often a larger set than the one used by dog breeders, but still much smaller than the entire genome.

This point can be illustrated with non-canine examples. Considerable genetic overlap exists not only between breeds of dogs but also between many anatomically and behaviorally distinct species. In the deer family, genetic variability is greater within some species than between some genera (Cronin, 1991). Some masked shrew populations are genetically closer to prairie shrews than they are to other masked shrews (Stewart et al., 1993). Only a minority of mallards cluster together on an mtDNA tree, the rest being scattered among black ducks (Avise et al., 1990). All six species of Darwin’s ground finches seem to form a genetically homogeneous genus with very little concordance between mtDNA, nuclear DNA, and morphology (Freeland & Boag, 1999). In terms of genetic distance, redpoll finches from the same species are not significantly closer to each other than redpolls from different species (Seutin et al., 1995). Among the haplochromine cichlids of Lake Victoria, it is extremely difficult to find interspecies differences in either nuclear or mitochondrial genes, even though these fishes are well differentiated morphologically and behaviorally (Klein et al., 1998). Neither mtDNA nor allozyme alleles can distinguish the various species of Lycaedis butterflies, despite clear differences in morphology (Nice & Shapiro, 1999). An extreme example is a dog tumor that has developed the ability to spread to other dogs through sexual contact: canine transmissible venereal sarcoma (CTVS). It looks and acts like an infectious microbe, yet its genes would show it to be a canid and, conceivably, some beagles may be genetically more similar to it than they are to Great Danes (Cochran, 2001; Yang, 1996).

Does this seem paradoxical? Let’s review how organisms become different from each other through natural selection. This typically happens when a group buds off from its parent population and colonizes a new environment. The environment may be another ecosystem, another mode of subsistence or even, as with CTVS, another form of existence. As the group adapts to its new environment, it will begin to diverge anatomically and behaviorally from its parent population, in part because the environmental boundary hinders gene flow between them but more importantly because the pressures of natural selection are no longer the same. The two populations will evolve differently because what is useful in one environment may not be in the other. And vice versa.

Will these differences in selection affect the entire genome? No. For one thing, most genes have low selective value, some being little more than junk DNA. For another, many genes code for traits that are equally useful in a wide range of environments. The ‘building block’ proteins of human flesh and blood are largely identical to those of non-human primates and sometimes even non-primate mammals (King & Wilson, 1975).

Thus, only a fraction of the genome changes when one population differentiates from another in response to differences in natural selection. The rest remains unchanged, either because the genes have little selective value or because they handle adaptive problems that are common to both populations. Over most of the genome, then, variability is due not to adaptive differences created by different selection pressures but rather to non-adaptive variations that similar selection pressures have left in place.

Of course, once the two populations have become reproductively isolated, they will no longer accumulate the same non-adaptive variations and their entire genomes will drift steadily apart. But this takes time. Redpoll finches diverged into two species some 50,000 years ago and have distinct phenotypes, yet their mitochondrial DNA reveals a single undifferentiated gene pool (Seutin et al., 1995). It’s no surprise, then, that human populations exhibit so much genetic overlap. They began to move apart only 40,000 or so years ago (Pritchard et al., 1999).

References

Avise, J.C., C.D. Ankney, and W.S. Nelson. (1990). Mitochondrial gene trees and the evolutionary relationship of mallard and black ducks. Evolution, 44, 1109-1119.

Cochran, G. (2001). Personal communication.

Coppinger, R. and R. Schneider (1995). Evolution of working dogs. In J. Serpell (ed.), The Domestic Dog: Its Evolution, Behaviour and Interactions with People. Cambridge: Cambridge University Press, pp. 21-47.

Cronin, M. (1991). Mitochondrial-DNA phylogeny of deer (Cervidae). Journal of Mammalogy, 72, 533-566.

Freeland, J.R. and P.T. Boag. (1999). The mitochondrial and nuclear genetic homogeneity of the phenotypically diverse Darwin’s ground finches. Evolution, 53, 1553-1563.

Hawks, J., E.T. Wang, G.M. Cochran, H.C. Harpending, and R.K. Moyzis. (2007). Recent acceleration of human adaptive evolution. Proceedings of the National Academy of Sciences (USA) early view.

King, M-C. and A.C. Wilson. (1975). Evolution at two levels in humans and chimpanzees. Science, 188, 107-116.

Klein, J., A. Sato, S. Nagl, and C. O’hUigin. (1998). Molecular trans-species polymorphism. Annual Review of Ecology and Systematics, 29, 1-21.

Lewontin, R.C. (1972). The apportionment of human diversity. Evolutionary Biology, 6, 381-398.

Nice, C.C. and A.M. Shapiro. (1999). Molecular and morphological divergence in the butterfly genus Lycaeides (Lepidoptera: Lycaenidae) in North America: evidence of recent speciation. Journal of Evolutionary Biology, 12, 936-950.

Pritchard, J.K., M.T. Seielstad, A. Perez-Lezaun, and M.W. Feldman. (1999). Population growth of human Y chromosomes: A study of Y chromosome microsatellites.” Molecular Biology and Evolution, 16, 1791-1798.

Seutin, G., L.M. Ratcliffe, and P.T. Boag. (1995). Mitochondrial DNA homogeneity in the phenotypically diverse redpoll finch complex (Aves: Carduelinae: Carduelis flammea-hornemanni). Evolution, 49, 962-973.

Stewart, D.T., A.J. Baker, and S.P. Hindocha. (1993). Genetic differentiation and population structure in Sorex Haydeni and S. Cinereus. Journal of Mammalogy, 74, 21-32.

Yang, T.J. (1996). Parasitic protist of metazoan origin, Evolutionary Theory, 11, 99-103.