Tuesday, March 24, 2020

The myth of selective neutrality

Paleolithic tent (Wikicommons - Michal Mañas). Did Europeans lose haplogroup U because they were replaced by farmers from the south? Or because they needed less energy for body heat?

Blood group systems have long been used to reconstruct prehistory. A good example is the Diego antigen. One of its alleles, DI*A, has helped us chart the prehistory of indigenous peoples in the Americas. Among other things, we have learned that most of them originated in Siberia some 12,000 years ago. This is not the case with the Eskimo-Aleut and Na-Dene peoples, who seem to have entered North America later. 

It’s assumed here that the Diego antigen has mutated at a steady rate and that the mutations have displaced earlier ones at a steady rate. So this antigen can act as a clock. If two populations have separated from each other, we can estimate their time of separation by measuring the mean genetic difference between them at the Diego antigen.

The "clock" assumption has its limitations. Diego mutations are neither kept nor lost at a constant rate. Both processes can be slowed down or speeded up by natural selection: 

Our study also revealed a significant correlation between DI*A allele frequency and warm tropical conditions, domesticated crop type, and presence of disease-carrying vector species. The circumscribed areas defined by these factors compose a mosaic of specific biocenoses and pathocenoses. It is thus reasonable to consider natural selection in the distribution of human genetic polymorphisms. (Bégat et al. 2015)

It's widely believed that all blood groups have the same survival value, so differences between them should be "selectively neutral." That belief is mistaken. In fact, nothing in the genome is truly of neutral value, not even noncoding genes that supposedly do nothing. Even if a gene doesn't code for anything, it still affects the spatial configuration of genes on the chromosome, thus altering how one gene may regulate another. 

According to a recent study, 80% of our genome has some kind of function, even noncoding genes (The ENCODE Project Consortium 2012). Indeed, such genes may have disproportionately contributed to human evolution. Comparison of our genome with other primate genomes has shown that almost all human-specific deletions are in noncoding regions (Bae et al. 2015). Furthermore, DNA is mostly noncoding in human accelerated regions (HARs)—genomic regions that have been well conserved throughout vertebrate evolution but are strikingly different in humans, perhaps in ways that alter how coding genes regulate each other (Bae et al. 2015). This would be consistent with the belief that our ancestors evolved largely through new ways of regulating existing systems, particularly the pace and timing of development (King and Wilson 1975).

Loss of haplogroup U: population replacement or change in natural selection?

Let's now look at haplogroup U. This, too, is assumed to be "selectively neutral" and is used to reconstruct prehistory, specifically the replacement of hunter-gatherers by farmers in Europe. Haplogroup U is a group of mitochondrial genes that was widespread among Mesolithic hunter-gatherers throughout Europe and is now common only among the Sami of Finland and the Mansi of northwestern Siberia, both of whom were hunter-gatherers until recently (Derbeneva et al. 2002). Indeed, according to ancient mtDNA from central and western Europe, the population frequency of haplogroup U shows a sharp break at the time boundary between late hunter-gatherers and early farmers (Bramanti et al. 2009). That break strongly suggests that European hunter-gatherers were largely replaced by farmers spreading into Europe from the Middle East.

Yet things are not always as they seem. In Denmark, haplogroup U persisted at high frequencies long after the transition to farming, in fact as late as the Early Iron Age (Melchior et al. 2010). In Latvia and Ukraine it persisted into Neolithic times (Jones et al. 2017).

Perhaps haplogroup U disappeared because it ceased to be adaptive and was removed by natural selection. This haplogroup shifts the energy balance away from ATP synthesis and toward production of body heat—a useful cold adaptation for hunter-gatherers, who had to sleep in makeshift shelters and pursue game animals in all kinds of weather (Balloux et al. 2009; Montiel-Sosa et al. 2006). Farmers slept in a warmer environment and could more easily plan their outdoor activities.

This being said, the loss of haplogroup U was not the only genetic change across the Mesolithic-Neolithic divide. Were those other changes due to natives being replaced by farmers from the Middle East? Or was natural selection again responsible? Researchers have tried to exclude the second cause by examining how noncoding genes changed across the divide, on the assumption that such genes are generally non-functional and make no difference to one’s chances of survival and reproduction. As we've seen, that assumption is unfounded.

Clearly, some of this genetic change was due to natural selection. I mentioned the shift in energy balance, but there were others. Farmers had less need for odor recognition, monotony avoidance, and sensation seeking (Majid and Kruspe 2018; Zuckerman 2008). They also had to process reciprocal obligations with a larger number of people while interacting less, on average, with each person. All in all, farming did not impose the same demands on mind and body. Going from one way of life to the other required many physiological adjustments.

To explain the genetic divide between hunter-gatherers and farmers, we should also allow for founder effects. When bands of hunter-gatherers are given the opportunity, only a few will choose to become farmers. Because this minority is a small sample of the hunter-gatherer gene pool, the new farming population will differ genetically from the previous one in many random ways.


When reconstructing the past, particularly the transition from hunting and gathering to farming, we shouldn't interpret genetic change solely in terms of one population replacing another. Some of the change may also be due to a new regime of natural selection, as well as founder effects.

I once made this point to Greg Cochran, and his reply was that changes in natural selection couldn't possibly account for all of the genetic change we see in ancient DNA between late hunter-gatherers and early farmers. True, but that's not my point. Some population replacement did happen, but its magnitude is exaggerated by a methodology that attributes all genetic change to that one factor alone. 

Interview with Grégoire Canlorbe

I was recently interviewed by Grégoire Canlorbe, a young French author and scholar. The interview covers a variety of topics and can be read in its entirety (in two parts) at American Renaissance:


Une traduction française est disponible sur le site Evopsy de Philippe Gouillou :



Bae, B-I., D. Jayaraman, and C.A. Walsh. (2015). Genetic changes shaping the human brain. Developmental Cell 32: 423-434. 

Balloux F., L.J. Handley, T. Jombart, H. Liu, and A. Manica. (2009). Climate shaped the worldwide distribution of human mitochondrial DNA sequence variation. Proceedings of the Royal Society B. Biological Sciences 276: 3447-3455. 

Bégat, C., Bailly, P., Chiaroni, J., & Mazières, S. (2015). Revisiting the Diego Blood Group System in Amerindians: Evidence for Gene-Culture Comigration. PloS one 10(7), e0132211.

Bramanti, B., M.G. Thomas, W. Haak, M. Unterlaender, P. Jores, K. Tambets, I. Antanaitis-Jacobs, M.N. Haidle, R. Jankauskas, C.J. Kind, et al. (2009). Genetic discontinuity between local hunter-gatherers and Central Europe's first farmers. Science 326: 137-140.

Derbeneva, O.A., E.B. Starikovskaya, D.C. Wallace, and R.I. Sukernik, (2002). Traces of early Eurasians in the Mansi of Northwest Siberia revealed by mitochondrial DNA analysis. American Journal of Human Genetics 70: 1009-1014. 

Jones, E.R., G. Zarina, V. Moiseyev, E. Lightfoot, P.R. Nigst, A. Manica, et al. (2017). The Neolithic transition in the Baltic was not driven by admixture with early European farmers. Current Biology 27(4): 576-582.

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

Majid, A., and N. Kruspe. (2018). Hunter-gatherer olfaction is special. Current Biology 28: R108-R110. 

Melchior, L., N. Lynnerup, H.R. Siegismund, T. Kivisild, and J. Dissing. (2010). Genetic diversity among ancient Nordic populations. PLoS One 5(7): e11898

Montiel-Sosa, F., E. Ruiz-Pesini, J.A. Enriquez, A. Marcuello, C. Diez-Sanchez, J. Montoya, D.J. Wallace, and M.J. López-Pérez, (2006). Differences of sperm motility in mitochondrial DNA haplogroup U sublineages. Gene 368: 21-27.

The ENCODE Project Consortium. (2012). An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57-74 

Zuckerman, M. (2008). Genetics of Sensation Seeking. In J. Benjamin, R.P. Ebstein, and R.H. Belmaker (Eds) Molecular Genetics and the Human Personality, (pp. 193-210). Washington D.C.: American Psychiatric Publishing Inc.


Unknown said...

The interview at Amren was really great!

Mihir Mane said...

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