Friday, July 9, 2021

Lewontin's legacy


Lewontin assumed that genetic diversity between populations is qualitatively similar to genetic diversity within populations. So comparing the two would be like comparing apples with apples. He was wrong. The second kind of diversity is less functionally significant.



The geneticist Richard Lewontin died last Sunday at the age of 92. He became prominent during the 1970s, particularly through his 1972 paper "The Apportionment of Human Diversity." Using data from blood groups, serum proteins, and red blood cell enzymes, he found far more genetic diversity within human populations than between them:


The results are quite remarkable. The mean proportion of the total species diversity that is contained within populations is 85.4%, with a maximum of 99.7% for the Xm gene, and a minimum of 63.6% for Duffy. Less than 15% of all human genetic diversity is accounted for by differences between human groups!


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.


His reasoning seems sound. It ignores, however, two aspects of population genetics:


1. Genetic differences between populations are qualitatively different from genetic differences within populations. A population boundary is usually a boundary between different environments, either natural environments or cultural environments. It is thus a boundary between different pressures of natural selection and, hence differences in adaptation. An allele may work just fine on one side of the boundary, but not so well on the other side. Conversely, genetic diversity within a population is less meaningful because the end result tends to be the same. Everyone is adapting to the same environment. Genetic differences are less likely to produce real functional differences.


2. Genetic differences vary considerably in their functional significance, with the overwhelming majority having little or none. Many of these differences are found in junk DNA.


Lewontin discovered the obvious. Most genetic differences have little or no functional significance, and such differences account for most of the diversity within human populations. The more a genetic difference has real consequences, the less likely it will be found within a population because that is where the pressures of selection are uniform. It will more likely be found at a population boundary where the pressures of selection are different.


We see this, for example, in dog breeds. Although they differ considerably in anatomy and behavior, they are barely discernable in the genetic data. There is much more diversity within breeds than between them:


... 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. ... 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)


Well, dog breeds have been created through human-directed selection. What about subspecies that have arisen through natural selection? We see the same fuzziness, not only between subspecies but also between many sibling species that are anatomically distinct. In the deer family, genetic diversity 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 while showing 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 they are to sibling species (Seutin et al. 1995). Different species of haplochromine cichlids cannot be easily told apart by means of nuclear or mitochondrial genes, yet they 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 spreads through sexual contact: canine transmissible venereal sarcoma. It looks and acts like an infectious pathogen, yet its genes would show it to be a canid, and some beagles may be genetically more similar to it than they are to Great Danes (Yang 1996; see Frost 2011 for a full discussion).


When populations diverge under the impact of divergent pressures of natural selection, changes initially occur only within a fraction of the genome. Later, with the passage of time, the two populations will drift apart over the rest of the genome. But the human species is still young. The genetic split between Africans and non-Africans goes back only 60,000 years, and other splits are younger still.


This doesn't mean that genetic diversity between human populations is trivial. In fact, almost the opposite is true. It is the diversity within populations that is largely trivial.





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.


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.


Frost, P. (2011). Human nature or human natures? Futures 43: 740-748.  


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.


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.


Bruce said...

Excellent. Best brief summary of this important topic.

Commenter/Anon said...

You could test this empirically by checking whether Fst is higher at coding and regulatory variants than at neutral variants. As far as I know the opposite is the case. So this blogpost seems pretty dumb.

Peter Frost said...

"As far as I know" ... Could you please provide a reference?

I once had a boss who would make fun of that way of speaking. "You either know or you don't know. There's no halfway!"

Of course, most coding variants are of low selective value anyway (as are most genes). So the difference between those variants and non-coding ones wouldn't be great.

Bill Jones said...

I keep coming back to this piece to see if there are any new, equally excellent analyses and am disappointed to see there are not.