Did women jumpstart recent cognitive evolution?

Scatter plots of frequencies of CASC5 variants by sex (Shi et al. 2017). During the last ice age, natural selection favored an increase in the gray matter of ancestral East Asians ... primarily in women.

Back in 2005 there was much interest in genes that regulate brain size, particularly in the ways they varied geographically within our species. It was found that two of these genes, Microcephalin and ASPM, continued to evolve as modern humans spread out of Africa. The latest variant of Microcephalin arose some 37,000 years ago in Eurasia and is still largely confined to the indigenous peoples of Eurasia and the Americas (Mekel-Bobrov et al. 2005). The latest variant of ASPM appeared even later, some 5,800 years in the Middle East (Evans et al. 2005).

Interest fell off when no association could be shown between the new variants and IQ or brain size (Mekel-Bobrov et al. 2007; Rushton et al. 2007; see also Frost 2020). Since then, we have learned that the new ASPM variant is associated with a larger cerebral cortex, and not a larger brain as a whole. Overall brain volume seems to be constrained in modern humans, perhaps by the breadth of a woman's pelvis during childbirth or simply by the high metabolic costs of brain tissue (Ali and Meier 2008; Frost 2020). As for the lack of an association with IQ, we now know that IQ correlates poorly or not at all with some cognitive abilities, like executive function and face recognition.

But what do the new variants actually do? Perhaps a specialized mental task.  It has been suggested that the new ASPM variant assists the brain in processing non-tonal language or alphabetical script (Dediu and Ladd 2007; Frost 2007).

CASC5, another gene for brain growth

Interest has since grown in another gene that regulates brain growth, CASC5. Like Microcephalin and ASPM, it has undergone recent evolution in the modern human lineage:

[...] the CASC5 gene contains mutations in modern humans, but not in Denisovans (Meyer et al. 2012) and this gene also shows distinct sequence divergence between modern humans and Neanderthals (Prufer et al. 2014). These data suggest that CASC5 is an important gene for human neurogenesis, and may harbor modern human specific mutations contributing to the recent evolutionary change of the human brain. (Shi et al. 2017)

Shi et al. (2017) found evidence of recent evolutionary change. Specifically, two nucleotides of CASC5 have been replaced with a new variant in all modern humans. Six other nucleotides have become polymorphic, with some people having the new variants and others not. These polymorphisms show regional differences:

- In four of the polymorphisms, the new variant has a much higher frequency in East Asians than in Europeans or Africans.

- In one polymorphism, it has a much higher frequency in Europeans than in the other two regional groups.

- The remaining polymorphism shows no differences in frequency between the three regional groups.

By and large, the new variants have been under strong positive selection, particularly among East Asians. When the authors examined the six polymorphisms, they found signals of selection for five of them in East Asians and for one in Europeans.

The new variants and brain characteristics

The authors then looked for correlations between the new variants and certain characteristics of the brain, specifically total brain volume, gray matter volume, and white matter volume. To this end, 267 healthy participants were recruited for brain imaging (Han Chinese, 178 females and 89 males, mean age 35.4 ± 12.5 years). All of them were free from mental disorders, drug abuse, alcohol dependence, and brain injury.

Gray matter was significantly larger in participants with the new variant than in those with the ancestral variant at five of the nucleotide sites, including the four polymorphic ones—the same ones that showed differences in variant frequency between East Asians and Europeans. When the authors examined the one polymorphism whose variants were equally common in East Asians, Europeans, and Africans, they found no brain differences between participants with the new variant and those with the ancestral one.

When the authors broke their data down by sex, they found that the new variants were significantly associated with a higher volume of gray matter only in women, not in men, although men seemed to trend in the same direction. The authors suggest that this effect would be significant in men if the number of male participants were larger. Probably. But it seems to me there would still be a sex difference, the number of participants being already large enough.

Ice age origin of the new variants

The authors say the new variants became prevalent "after modern humans migrated out of Africa less than 100,000 years ago." We can narrow down the time range further. The new variants are also present at high frequencies among the indigenous peoples of North and South America; therefore, they must have become prevalent before ancestral Amerindians crossed into North America some 12,000 years ago, apparently in a population that was ancestral both to Amerindians and to East Asians. That would be long before the time of recorded history and even before the Holocene, at a time when northern Eurasia was experiencing glacial conditions.

Did those conditions select for cognitive ability? Cold, seasonal environments did impose new cognitive demands on early modern humans, first by increasing their need to plan ahead over a yearly cycle and second by providing them with new tasks: garment making, needlework, weaving, leatherworking, and kiln operation. Women performed those tasks because the environment offered them few opportunities for food gathering—the usual female activity before the advent of farming. They thus moved into artisanal tasks that not only required greater cognitive ability but also offered much potential for further development. This was the "original industrial revolution" and it was led by women (Frost 2019a).

We can better understand this sexual division of labor by studying northern hunter-gatherers of recent times. According to a cross-cultural study, if women are less involved in food gathering, they specialize in activities unrelated to food procurement, i.e., house building, leatherworking, and burden carrying (Waguespack 2005). A study of two Inuit groups found the highest degree of technological complexity in garment making and shelter building, both of which are wholly or largely women's work (Oswalt 1976). Cold environments thus change the sexual division of labor among hunter-gatherers in a crucial way: while men continue to be food providers, women develop new technologies.

These findings may explain the recent evolution of CASC5: women were the focus of selection for cognitive ability during Ice Age times. But why was the selection stronger among ancestral East Asians than among ancestral Europeans? It looks like the climate at that time was more severe in northern Asia than in northern Europe. Europe benefited from the moderating influence of the Atlantic, which made for a milder and moister climate. Conditions were much colder and drier in northern Asia.

The evolution of human intelligence cannot be reduced to a single unified theory. Cold environments emancipated women from the mental straitjacket of food gathering, thus putting humans on the path to social complexity. That path, however, would take them to latitudes farther south in temperate and even tropical environments where they would be exposed to new cognitive demands. With the end of hunting, men moved not only into farming but also into the artisanal activities that women had developed. The same period saw a decline in brain volume that was greater in women than in men—an indication that cognitive demands were particularly high before the Holocene, and even more so for women (Frost 2019b).

The Holocene thus saw northern populations expand southward and eventually cover almost all of Eurasia, North Africa, Oceania, and the Americas. Those populations had a cognitive advantage that made them better able to exploit the social complexity emerging farther south. This point was made by Darwin's colleague Alfred Russel Wallace:

So when a glacial epoch comes on, some animals must acquire warmer fur, or a covering of fat, or else die of cold. Those best clothed by nature are, therefore, preserved by natural selection. Man, under the same circumstances, will make himself warmer clothing, and build better houses; and the necessity of doing this will react upon his mental organisation and social condition [...] a hardier, a more provident, and a more social race would be developed, than in those regions where the earth produces a perennial supply of vegetable food, and where neither foresight nor ingenuity are required to prepare for the rigours of winter. And is it not the fact that in all ages, and in every quarter of the globe, the inhabitants of temperate have been superior to those of tropical countries? All the great invasions and displacements of races have been from North to South, rather than the reverse.

References

Ali, F. and R. Meier. (2008). Positive selection in ASPM is correlated with cerebral cortex evolution across primates but not with whole brain size. Molecular Biology and Evolution 25(11): 2247-2250.

https://www.researchgate.net/profile/Rudolf_Meier/publication/23185977_Positive_Selection_in_ASPM_Is_Correlated_with_Cerebral_Cortex_Evolution_across_Primates_but_Not_with_Whole-Brain_Size/links/00b7d53ad237958edd000000.pdf

Dediu, D., and R. Ladd. (2007). Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and Microcephalin. Proceedings of the National Academy of Sciences 104(26): 10944-10949

https://langev.com/pdf/dediu07linguisticTonePNAS.pdf

Evans, P. D., Gilbert, S. L., Mekel-Bobrov, N., Vallender, E. J., Anderson, J. R., Vaez-Azizi, L. M., et al. (2005). Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans. Science 309: 1717-1720.

http://web.stanford.edu/class/cs273a/papers.spr07/lecture15/Microencephalin.pdf

Frost, P. (2007). The spread of alphabetical writing may have favored the latest variant of the ASPM gene. Medical Hypotheses 70: 17-20.

http://www.sciencedirect.com/science/article/pii/S0306987707003234

Frost, P. (2019a). The Original Industrial Revolution. Did Cold Winters Select for Cognitive Ability? Psych 1(1): 166-181

https://doi.org/10.3390/psych1010012

Frost, P. (2019b). Why did brain size decrease after the ice age? Evo and Proud, July 6

https://evoandproud.blogspot.com/2019/07/why-did-brain-size-decrease-after-ice.html

Frost, P. (2020). A second look at ASPM. Evo and Proud, April 14

https://evoandproud.blogspot.com/2020/04/a-second-look-at-aspm.html

Mekel-Bobrov, N., S.L. Gilbert, P.D. Evans, E.J. Vallender, J.R. Anderson, R.R. Hudson, S.A. Tishkoff and B.T. Lahn. (2005). Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens. Science 309: 1720-1722

https://www.researchgate.net/publication/7611130_Ongoing_Adaptive_Evolution_of_ASPM_a_Brain_Size_Determinant_in_Homo_Sapiens

Mekel-Bobrov, N., D. Posthuma, S.L. Gilbert, P. Lind, M.F. Gosso, et al. (2007). The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence. Human Molecular Genetics 16(6): 600-608.

https://academic.oup.com/hmg/article/16/6/600/610971

Oswalt, W.H. (1976). An Anthropological Analysis of Food-Getting Technology, 1st ed.; John Wiley and Sons: New York, NY, USA.

Rushton, J.P., P.A. Vernon, and T.A. Bons. (2007). No evidence that polymorphisms of brain regulator genes Microcephalin and ASPM are associated with general mental ability, head circumference or altruism. Biology Letters-UK 3(2): 157-60.

https://royalsocietypublishing.org/doi/full/10.1098/rsbl.2006.0586

Shi, L., Hu, E., Wang, Z. et al. (2017). Regional selection of the brain size regulating gene CASC5 provides new insight into human brain evolution. Human Genetics 136: 193-204. https://doi.org/10.1007/s00439-016-1748-5

http://ir.ioz.ac.cn/bitstream/000000/12812/1/Regional%20selection%20of%20the%20brain%20size%20regulati1.pdf

Waguespack, N.M. (2005). The organization of male and female labor in foraging societies: Implications for early Paleoindian archaeology. American Anthropologist 107: 666-676.

https://pdfs.semanticscholar.org/8e50/02b23a25d1a97054f8bf9b8b852d2151a093.pdf

Wallace, A.R. (1864). The Origin of Human Races and the Antiquity of Man deduced from the Theory of "Natural Selection." Journal of the Anthropological Society of London, 2, clviii-clxxxvii, Alfred Russel Wallace Classic Writings. Paper 6. http://digitalcommons.wku.edu/dlps_fac_arw/6

A new start

 

When geneticist Davide Piffer examined IQ-enhancing alleles at seven different genes, he found that their average prevalence differed among human populations, being highest in East Asians and lowest in Mbuti Pygmies (photo used with author's approval)

 

My weekly posts are now appearing on The Unz Review (http://www.unz.com/). By accepting Ron's invitation, I hope to reach a bigger audience and bring myself closer to other writers in the area of human biodiversity. When people work together, or simply alongside each other, minor differences can be ironed out and major differences narrowed or at least accepted good-naturedly. One thing I've learned is that academic debate can leave a legacy of hurt feelings. The impersonal can become personal, partly because people feel attached to their views and partly because views themselves can have personal impacts.

Working together also creates synergy. It becomes easier to identify research priorities, contact interested researchers, and end up with publishable findings. At present, most HBD research involves trawling through the literature and offering new interpretations. That's fine, but we need lab work as well. This point came up in a 2006 interview with geneticist Bruce Lahn:
 

A lot of researchers studying human population genetics and evolution are strictly data miners (i.e., they generate/publish no original data). There are limitations to such an approach, as it depends on the available data and prevents certain analyses from being performed. Do you expect to see more research groups turning into pure data mining labs in the future? Or will there still be a place for independent labs generating their own data (for example, resequencing a gene in multiple individuals to study the polymorphism)?

Given the explosion of genomic data in the last decade or so, which shows no sign of slowing down any time soon, there is likely to be a proliferation of pure data miners just because there is a niche for them. But I suspect that many interesting findings will still require the combination of data mining and wet experiments to provide key pieces of data not already available in public databases. In this regard, labs that can do both data mining and wet experiments can have an advantage over labs that can only do data mining. (Gene Expression, 2006)

Lab work will probably have to be offshored, not because it's cheaper to do elsewhere but because the "free world" is no longer the best place for unimpeded scientific inquiry.  A Hong Kong team is conducting a large-scale investigation into the genetics of intelligence, and nothing comparable is being done in either North America or Western Europe. Cost isn't the reason.

A few suggestions for research:

 

Human variation in IQ-enhancing alleles

We know that human intellectual capacity has risen through small incremental changes at very many genes, probably hundreds if not thousands. Have these changes been the same in all populations?

Davide Piffer (2013) has tried to answer this question by using a small subset of these genes. He began with seven SNPs whose different alleles are associated with differences in performance on PISA or IQ tests. Then, for fifty human populations, he looked up the prevalence of each allele that seems to increase performance. Finally, for each population, he calculated the average prevalence of these alleles at all seven genes.

The average prevalence was 39% among East Asians, 36% among Europeans, 32% among Amerindians, 24% among Melanesians and Papuan-New Guineans, and 16% among sub-Saharan Africans. The lowest scores were among San Bushmen (6%) and Mbuti Pygmies (5%). A related finding is that all but one of the alleles are specific to humans and not shared with ancestral primates.

Yes, he was using a small subset of genes that influence intellectual capacity. But you don't need a big number to get the big picture. If you dip your hand into a barrel of differently colored jelly beans, the colors you see in your hand will match well enough what's in the barrel. In any case, if the same trend holds up with a subset of 50 or so genes, it will be hard to say it's all due to chance.

 

Interaction between age and intellectual capacity

These population differences seem to widen after puberty, as Franz Boas noted a century ago (Boas, 1974, p. 234). It may be that general intelligence was largely confined to early childhood in ancestral humans, as a means to integrate information during the time of life when children become familiar with their surroundings. With increasing age, and familiarity, this learning capacity would shut down. When modern humans began to enter environments that had higher cognitive demands, natural selection may have favored retention of general intelligence in adulthood, just as it favored retention of the capacity to digest lactose wherever adults raised dairy cattle and drank milk.

After doing a principal component analysis on covariance between the above IQ-enhancing alleles and performance on IQ and Pisa tests, Piffer (2013) was able to identify three alleles that show the highest loading on the first component. Ward et al. (2014) have found that possession of these three alleles correlates with educational performance of 13 to 14 year old children. We now have a tool to measure the interaction between genes and age in the development of intellectual capacity, particularly during the critical period extending from pre-puberty to early adulthood.

 

Convergent evolution

Some human populations seem to have arrived at similar outcomes through different evolutionary trajectories. East Asians, for instance, resemble Western Europeans in their level of societal development, but this similar outcome has been achieved through a different mental and behavioral package, specifically lower levels of guilt and empathy with correspondingly higher levels of shame and prosocial behavior. In short, East Asians tend to enforce social rules more by external mediation (e.g., shaming, peer pressure, family discipline) than by internal control (e.g., guilt, empathy).

This difference probably reflects a mix of learned and innate predispositions, since natural selection favors whatever works, regardless of how hardwired it may or may not be. To the extent that these predispositions are hardwired, East Asians may be less able to cope with the sort of aloneness, anonymity, and individualism we take for granted.

It would be easy enough to study the neurological effects of social isolation on East Asians, and there is already suggestive evidence that such effects include unusual outbursts of psychotic behavior. It would be harder, however, to determine whether this malfunctioning has a heritable component.

 

Microcephalin - Why does its Eurasian allele increase brain volume?

Almost a decade ago, Bruce Lahn was among those who discovered that a gene involved in brain growth, Microcephalin, continued to evolve after modern humans had spread out of Africa. Its most recent allele arose some 37,000 years ago in Eurasia and is still largely confined to native Eurasians and Amerindians (Evans et al., 2005). Interest in this finding evaporated when no significant correlation was found between the Eurasian allele and higher scores on IQ tests (Mekel-Bobrov et al, 2007; Rushton et al., 2007). Nonetheless, a later study showed that this allele correlates with increased brain volume (Montgomery and Mundy, 2010).

The time of origin corresponds to the entry of modern humans into seasonal temperate environments. It also corresponds to the beginnings of Upper Paleolithic art—realistic 3D representations of game animals on stone, clay, bone, and ivory. The common denominator seems to be an increased capacity to store spatiotemporal information, i.e., the ability to imagine objects, particularly game animals, and how they move over space and time. If IQ tests fail to measure this capacity, it may be worthwhile to test carriers of this allele for artistic or map-reading skills.

 

ASPM - Does the Middle Eastern/West Eurasian allele assist processing of alphabetical script?

ASPM is another gene that regulates brain growth, and like Microcephalin it continued to evolve after modern humans had spread out of Africa, its latest allele arising about 6000 years ago somewhere in the Middle East. The new allele then proliferated within and outside this region, reaching higher incidences in the Middle East (37-52%) and in Europe (38-50%) than in East Asia (0-25%). Despite its apparent selective advantage, this allele does not seem to improve cognitive performance on standard IQ tests. On the other hand, there is evidence that it is associated with increased brain size (Montgomery and Mundy, 2010).

At present, we can only say that it probably assists performance on a task that exhibited the same geographic expansion from a Middle Eastern origin roughly 6000 years ago. The closest match seems to be the invention of alphabetical writing, specifically the task of transcribing speech and copying texts into alphabetical script. Though more easily learned than ideographs, alphabetical characters place higher demands on mental processing, especially under premodern conditions (continuous text with little or no punctuation, real-time stenography, absence of automated assistance for publishing or copying, etc.). This task was largely delegated to scribes of various sorts who enjoyed privileged status and probably superior reproductive success. Such individuals may have served as vectors for spreading the new ASPM allele (Frost, 2008; Frost, 2011).

 

Tay Sachs and IQ

Ashkenazi Jews have high incidences of certain neurological conditions, particularly Tay Sachs, Gaucher's disease, and Niemann-Pick disease. In the homozygous state these conditions are deleterious, but in the heterozygous state they may improve intellectual capacity by increasing neural axis length and branching. Cochran et al. (2006) argue that this improvement could amount to about 5 IQ points.

There was in fact a study in the 1980s to determine whether Tay-Sachs heterozygotes suffer from mental deficits (Kohn et al., 1988). The authors found no deficits but did not elaborate on whether performance was above-normal on the neuropsychological tests. They did mention that about two thirds of the Tay-Sachs heterozygotes had education beyond high school.

The raw data seem to be long gone, but it would not be difficult to repeat the study with a view to studying above-normal mental performance in heterozygotes and non-carriers.

 

References

Boas, F. (1974). A Franz Boas Reader. The Shaping of American Anthropology, 1883-1911, G.W. Stocking Jr. (ed.), Chicago: The University of Chicago Press.

 

Cochran, G., J. Hardy, and H. Harpending. (2006). Natural history of Ashkenazi intelligence, Journal of Biosocial Science, 38, 659-693.

http://harpending.humanevo.utah.edu/trial.link/Ashkenazi.pdf

 

Evans, P. D., Gilbert, S. L., Mekel-Bobrov, N., Vallender, E. J., Anderson, J. R., Vaez-Azizi, L. M., et al. (2005). Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans, Science, 309, 1717-1720.

http://www.fed.cuhk.edu.hk/~lchang/material/Evolutionary/Brain%20gene%20and%20race.pdf

 

Frost, P. (2008). The spread of alphabetical writing may have favored the latest variant of the ASPM gene, Medical Hypotheses, 70, 17-20.

http://www.sciencedirect.com/science/article/pii/S0306987707003234

Frost, P. (2011). Human nature or human natures? Futures, 43, 740-748. http://dx.doi.org/10.1016/j.futures.2011.05.017

 

Gene Expression. (2006). 10 Questions for Bruce Lahn.

http://www.gnxp.com/blog/2006/10/10-questions-for-bruce-lahn_10.php

Kohn, H., P. Manowitz, M. Miller, and A. Kling. (1988). Neuropsychological deficits in obligatory heterozygotes for metachromatic leukodystrophy, Human Genetics, 79, 8-12.

 

Mekel-Bobrov, N., Posthuma, D., Gilbert, S. L., Lind, P., Gosso, M. F., Luciano, M., et al. (2007). The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence, Human Molecular Genetics, 16, 600-608.

http://psych.colorado.edu/~carey/pdfFiles/ASPMMicrocephalin_Lahn.pdf

 

Montgomery, S. H., and N.I. Mundy. (2010). Brain evolution: Microcephaly genes weigh in, Current Biology, 20, R244-R246.

http://www.sciencedirect.com/science/article/pii/S0960982210000862

 

Piffer, D. (2013). Factor analysis of population allele frequencies as a simple, novel method of detecting signals of recent polygenic selection: The example of educational attainment and IQ, Mankind Quarterly, 54, 168-200.

http://emilkirkegaard.dk/en/wp-content/uploads/Factor-Analysis-of-Population-Allele-Frequencies-as-a-Simple-Novel-Method-of-Detecting-Signals-of-Recent-Polygenic-Selection-The-Example-of-Educational-Attainment-and-IQ.pdf 

 

Rushton, J. P., Vernon, P. A., and Bons, T. A. (2007). No evidence that polymorphisms of brain regulator genes Microcephalin and ASPM are associated with general mental ability, head circumference or altruism, Biology Letters, 3, 157-160.

http://semantico-scolaris.com/media/data/Luxid/Biol_Lett_2007_Apr_22_3(2)_157-160/rsbl20060586.pdf 

 

Ward, M.E., G. McMahon, B. St Pourcain, D.M. Evans, C.A. Rietveld, et al. (2014). Genetic variation associated with differential educational attainment in adults has anticipated associations with school performance in children. PLoS ONE 9(7): e100248. doi:10.1371/journal.pone.0100248

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0100248#pone-0100248-g002

The riddle of Microcephalin

 

World distribution of the recent Microcephalin allele. The prevalence is indicated in black and the letter 'D' refers to the 'derived' or recent allele (Evans et al., 2005)

 

Almost a decade ago, there was much interest in a finding that a gene involved in brain growth, Microcephalin, continued to evolve after modern humans had begun to spread out of Africa. The 'derived' allele of this gene (the most recent variant) arose some 37,000 years ago somewhere in Eurasia and even today is largely confined to the native populations of Eurasia and the Americas (Evans et al., 2005).

Interest then evaporated when no significant correlation was found between this derived allele and higher scores on IQ tests (Mekel-Bobrov et al, 2007; Rushton et al., 2007). Nonetheless, a later study did show that this allele correlates with increased brain volume (Montgomery and Mundy, 2010).

So what is going on? Perhaps the derived Microcephalin allele helps us on a mental task that IQ tests fail to measure. Or perhaps it boosts intelligence in some indirect way that shows up in differences between populations but not in differences between individuals.

The second explanation is the one favored in a recent study by Woodley et al. (2014). The authors found a high correlation (r = 0.79) between the incidence of this allele and a population's estimated mean IQ, using a sample of 59 populations from throughout the world. They also found a correlation with a lower incidence of infectious diseases, as measured by DALY (disability adjusted life years). They go on to argue that this allele may improve the body’s immune response to viral infections, thus enabling humans to survive in larger communities, which in turn would have selected for increased intelligence:

Bigger and more disease resistant populations would be able to produce more high intelligence individuals who could take advantage of the new cognitive opportunities afforded by the social and cultural changes that occurred over the past 10,000 years. (Woodley et al., 2014)

Bigger populations would also have increased the probability of “new intelligence-enhancing mutations and created new cognitive niches encouraging accelerated directional selection for the carriers of these mutations.” A positive feedback would have thus developed between intelligence and population density:

[…] the evolution of higher levels of intelligence during the Upper Paleolithic revolution some 50,000 to 10,000 ybp may have been necessary for the development of the sorts of subsistence paradigms (e.g. pastoralism, plant cultivation, etc.) that subsequently emerged. (Woodley et al., 2014)

 

 

What do I think?

I have mixed feelings about this study. Looking at the world distribution of this allele (see above map), I can see right away a much higher prevalence in Eurasia and the Americas than in sub-Saharan Africa. That kind of geographic distribution would inevitably correlate with IQ. And it would also correlate with the prevalence of infectious diseases.

Unfortunately, such correlations can be spurious. There are all kinds of differences between sub-Saharan Africa and the rest of the world. One could show, for instance, that per capita consumption of yams correlates inversely with IQ. But yams don't make you stupid.

More seriously, one could attribute the geographic range of this allele to a founder effect that occurred when modern humans began to spread out of Africa to other continents. In that case, it could be junk DNA with no adaptive value at all. There is of course a bit of a margin between its estimated time of origin (circa 37,000 BP) and the Out of Africa event (circa 50,000 BP), but that difference could be put down to errors in estimating either date.

No, I don't believe that a founder effect was responsible. A more likely cause would be selection to meet the cognitive demands of the First Industrial Revolution, when humans had to create a wider range of tools to cope with seasonal environments and severe time constraints on the tasks of locating, processing, and storing food. This allele might have helped humans in the task of imagining a 3D mental “template” of whatever tool they wished to make. Or it might have helped hunters store large quantities of spatio-temporal information (like a GPS) while hunting over large expanses of territory. Those are my hunches.

I don't want to pooh-pooh the explanation proposed in this study. At times, however, the authors' reasoning seems more than a bit strained. Yes, this allele does facilitate re-growth of neural tissue after influenza infections, probably via repair of damaged DNA, but the evidence for a more general role in immune response seems weak. More to the point, the allele’s time of origin (39,000 BP) doesn't correspond to a time when humans began to live in larger, more sedentary communities. This was when they were still hunter-gatherers and just beginning to spread into temperate and sub-arctic environments with lower carrying capacities. Human population density was probably going down, not up. It wasn't until almost 30,000 years later, with the advent of agriculture, that it began to increase considerably.

The authors are aware of this last point and note in it their paper. So we come back to the question: what could have been increasing the risk of disease circa 39,000 BP? The authors suggest several sources of increased risk: contact with archaic hominins (Neanderthals, Denisovans), domestication of wolves and other animals, increasing population densities of hunter-gatherers, and contact by hunter-gatherers with new environments. Again, this reasoning seems to push the envelope of plausibility. Yes, Neanderthals were still around in 39,000 BP, but they had already begun to retreat and by 30,000 BP were extinct over most of their former range. Yes, we have evidence of wolf domestication as early as 33,000 BP, but livestock animals were not domesticated until much later. Yes, there was a trend toward increasing population density among hunter-gatherers, but this was not until after the glacial maximum, i.e., from 15,000 BP onward. Yes, hunter-gatherers were entering new environments, but those environments were largely outside the tropics in regions where winter kills many pathogens. So disease risk would have been decreasing.

I don’t wish to come down too hard on this paper. There may be something to it. My fear is simply that it will steer researchers away from another possible explanation: the derived Microcephalin allele assists performance on a mental task that is not measured by standard IQ tests.

 

References

 

Evans, P. D., Gilbert, S. L., Mekel-Bobrov, N., Vallender, E. J., Anderson, J. R., Vaez-Azizi, L. M., et al. (2005). Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans, Science, 309, 1717-1720.

http://www.fed.cuhk.edu.hk/~lchang/material/Evolutionary/Brain%20gene%20and%20race.pdf

 

Mekel-Bobrov, N., Posthuma, D., Gilbert, S. L., Lind, P., Gosso, M. F., Luciano, M., et al. (2007). The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence, Human Molecular Genetics, 16, 600-608.

http://psych.colorado.edu/~carey/pdfFiles/ASPMMicrocephalin_Lahn.pdf

 

Montgomery, S. H., and N.I. Mundy. (2010). Brain evolution: Microcephaly genes weigh in, Current Biology, 20, R244-R246.

http://www.sciencedirect.com/science/article/pii/S0960982210000862

 

Rushton, J. P., Vernon, P. A., and Bons, T. A. (2007). No evidence that polymorphisms of brain regulator genes Microcephalin and ASPM are associated with general mental ability, head circumference or altruism, Biology Letters, 3, 157-160.

http://semantico-scolaris.com/media/data/Luxid/Biol_Lett_2007_Apr_22_3(2)_157-160/rsbl20060586.pdf

 

Woodley, M. A., H. Rindermann, E. Bell, J. Stratford, and D. Piffer. (2014). The relationship between Microcephalin, ASPM and intelligence: A reconsideration, Intelligence, 44, 51-63.

http://www.sciencedirect.com/science/article/pii/S0160289614000312  

Review of 2010

Drinking from the wrong chalice? By his mid-40s, Michael Jackson had skin like parchment.

The end of 2010 is drawing nigh, and the time has come to review my predictions from last year.

Brain growth genes

Back in 2005, it was found that human populations vary considerably at two genes, ASPM and microcephalin, that control the growth of brain tissue. The finding seemed to be ‘huge’ in its implications. Then, it all fizzled out. No correlation could be found between variation at either gene and differences in mental ability or head circumference (Mekel-Bobrov et al., 2007; Rushton et al., 2007).

A recent study has now shown that ASPM and several other genes (MCPH1, CDK5RAP2, CENPJ) do in fact influence growth of brain tissue, specifically cortical tissue.

… In 2010, we’ll probably see further developments in this area. Stay tuned.

This year did see further developments. Interestingly, these gene loci seem to interact with sex and ethnicity in their effects:

[In a Norwegian study by Rimol et al.] for each of the 15 positive SNPs, the association was sex-specific with all significant results for CDK5RAP2 SNPs being found only in males, whilst the significant results for MCPH1 and ASPM were only found in females.

The second study, by Wang et al., only considered variation in the coding sequence of MCPH1 but found that one non-synonymous SNP is associated with male cranial volume but not female cranial volume in a Chinese population of nearly 900 individuals, supporting a role for sex in the action of microcephaly genes. Intriguingly, it also suggests that SNPs in the same locus can have opposite effects in males and females, as for MCPH1 an exonic SNP contributes to Chinese male cranial volume whilst intronic SNPs and SNPs downstream of the coding sequence are associated with Norwegian female brain size. As the authors discuss, these results strongly suggest some microcephaly variants may influence brain development dependent on hormonal background or through interactions with genes which are differentially expressed between the sexes, potentially contributing to sex specific differences in brain structure. (Montgomery & Mundy 2010)

But why did earlier studies find nothing?

First, many of the previous studies only tested for associations with the few, recently derived ASPM and MCPH1 haplotypes which were the focus of claims of recent positive selection, while both Rimol et al. and Wang et al. consider a larger number of SNPs for which there is no a priori evidence for selection. Second, despite the possibility of deriving clear hypotheses of what phenotypes these loci should affect, many previous studies examined traits that are, at best, not directly relevant (e.g. IQ or altruism) or quite distantly removed (e.g. adult head circumference). (Montgomery & Mundy 2010)

Many people had thought that all variation in mental capacity shows up on IQ tests. So they threw in the towel once it became apparent that IQ does not vary with genetic variation at these loci.

So how do these loci affect mental capacity? I’ve argued that the most recent ASPM variant seems to be associated with the spread of alphabetical writing. It may thus assist the visual cortex in recognizing, storing, and processing strings of alphabetical script (Frost 2008).

Alternatively, Dediu and Ladd (2007) have argued that ASPM and microcephalin variants correlate with use or non-use of tone languages. This hypothesis has been tested with Chinese, Korean, Hmong, and American Caucasians who had little training in tone recognition, i.e., they were not musicians and did not engage in singing or instrument playing. The Chinese and Koreans consistently outperformed the other participants when asked to identify the relative distance between two tones. The Hmong showed no such advantage, even though they shared the ASPM and microcephalin characteristics of the Chinese and Koreans (Hove et al., 2010). Thus, while some East Asian populations apparently are better at processing differences in pitch, this aptitude seems to be unrelated to ASPM or microcephalin.

Early modern human genome

Scientists have retrieved mtDNA from a 30,000 year-old hunter-gatherer from Kostenki, Russia. This seems to be part of a trend to study the genome of early modern humans.

The Kostenki mtDNA genome was entirely sequenced, despite problems that seemed intractable (difficulties in distinguishing between early modern human DNA and contamination from present-day human DNA). The authors concluded: “With this approach, it may even become possible to analyze the nuclear genomes of early modern humans” (Krause et al., 2010).

This development is indeed promising. If we can compare early modern DNA with present-day nuclear DNA, we’ll find out the exact genetic changes, especially those in neural wiring, that led to the ‘big bang’ of modern human evolution some 80,000 to 60,000 years ago. Unfortunately, this ‘big bang’ almost certainly took place in Africa, where the climate is much less conducive to DNA preservation.

Ethnic differences in vitamin D metabolism

This year will see further evidence that natural selection has caused differences in metabolism among different human populations, including vitamin D metabolism.

For instance, many populations have long been established at latitudes where vitamin-D synthesis is impossible for most of the year. Some of these populations can get vitamin D from dietary sources (e.g., fatty fish) but most cannot. In these circumstances, natural selection seems to have adjusted their metabolism to reduce their vitamin-D requirements. We know that the Inuit have compensated for lower production of vitamin D by converting more of this vitamin to its most active form (Rejnmark et al., 2004). They also seem to absorb calcium more efficiently, perhaps because of a different vitamin-D receptor genotype (Sellers et al., 2003). Even outside the Arctic zone, there seem to be differences in vitamin-D metabolism from one population to another. In particular, vitamin-D levels seem to be generally lower in darker-skinned populations (Frost, 2009).

… Unfortunately, our norms for adequate vitamin intake are based on subjects or populations of European origin. We are thus diagnosing vitamin-D deficiency in non-European individuals who are, in fact, perfectly normal. This is particularly true for African Americans, nearly half of whom are classified as vitamin-D deficient, even though few show signs of calcium deficiency—which would be a logical outcome. Indeed, this population has less osteoporosis, fewer fractures, and a higher bone mineral density than do Euro-Americans, who generally produce and ingest more vitamin D (Frost, 2009).

… What will be the outcome of raising vitamin-D levels in these populations? Keep in mind that we are really talking about a hormone, not a vitamin. This hormone interacts with the chromosomes and gradually shortens their telomeres if concentrations are either too low or too high. Tuohimaa (2009) argues that optimal levels may lie in the range of 40-60 nmol/L. In non-European populations the range is probably lower. It may also be narrower in those of tropical origin, since their bodies have not adapted to the wide seasonal variation of non-tropical humans.

If this optimal range is continually exceeded, the long-term effects may look like those of aging …

I hope that people of African or Native origin will resist the vitamin-D siren song. Otherwise, many of them will become shriveled-up husks by their mid-40s … just like Michael Jackson.

Evidence continued to mount this year that vitamin-D metabolism differs by ethnicity. For risk of atherosclerosis, the optimal range is lower among African Americans than among European Americans. A sample of African Americans showed a positive correlation between calcified plaque formation and blood levels of vitamin D (25(OH)D), despite a negative correlation among European Americans over the same range (Freedman et al., 2010).

Another study of African Americans found that blood levels of 25(OH)D decreased linearly with increasing African ancestry, the decrease being 2.5-2.75 nmol/L per 10% increase in African ancestry. Sunlight and diet were 46% less effective in raising these levels among subjects with high African ancestry than among those with low/medium African ancestry (Signorello et al. 2010).

The New York Times has recently covered the growing unease with vitamin D supplements:

The very high levels of vitamin D that are often recommended by doctors and testing laboratories — and can be achieved only by taking supplements — are unnecessary and could be harmful, an expert committee says.

… The 14-member expert committee was convened by the Institute of Medicine, an independent nonprofit scientific body, at the request of the United States and Canadian governments. It was asked to examine the available data — nearly 1,000 publications — to determine how much vitamin D and calcium people were getting, how much was needed for optimal health and how much was too much.

… Some labs have started reporting levels of less than 30 nanograms of vitamin D per milliliter of blood as a deficiency. With that as a standard, 80 percent of the population would be deemed deficient of vitamin D, Dr. Rosen said. Most people need to take supplements to reach levels above 30 nanograms per milliliter, he added.

But, the committee concluded, a level of 20 to 30 nanograms [50 to 75 nmol/L] is all that is needed for bone health, and nearly everyone is in that range.

… It is not clear how or why the claims for high vitamin D levels started, medical experts say. First there were two studies, which turned out to be incorrect, that said people needed 30 nanograms of vitamin D per milliliter of blood, the upper end of what the committee says is a normal range. They were followed by articles and claims and books saying much higher levels — 40 to 50 nanograms or even higher — were needed.

After reviewing the data, the committee concluded that the evidence for the benefits of high levels of vitamin D was “inconsistent and/or conflicting and did not demonstrate causality.”

Evidence also suggests that high levels of vitamin D can increase the risks for fractures and the overall death rate and can raise the risk for other diseases. (Kolata 2010)

H/T to Tod

References

Dediu, D., and D.R. Ladd (2007). Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and Microcephalin. Proceedings of the National Academy of Sciences, 104, 10944-10949.

Freedman B.I., L.E. Wagenknecht, K.G. Hairston KG et al. (2010). Vitamin D, adiposity, and calcified atherosclerotic plaque in African-Americans. Journal of Clinical Endocrinology & Metabolism, 95, 1076-1083.

Frost, P. (2009). Black-White differences in cancer risk and the vitamin-D hypothesis, Journal of the National Medical Association, 101, 1310-1313.

Frost, P. (2008). The spread of alphabetical writing may have favored the latest variant of the ASPM gene, Medical Hypotheses, 70, 17-20.

Hove, M.J., M.E. Sutherland, and C.L. Krumhansl. (2010). Ethnicity effects in relative pitch, Psychonomic Bulletin & Review, 17, 310-316.

Kolata, G. (2010). Report Questions Need for 2 Diet Supplements, The New York Times, November 29, 2010
http://www.nytimes.com/2010/11/30/health/30vitamin.html?_r=2&hp

Krause, J., A.W. Briggs, M. Kircher, T. Maricic, N. Zwyns, A. Derevianko, and S. Pääbo. (2010). A Complete mtDNA genome of an early modern human from Kostenki, Russia, Current Biology 20, 231–236.

Mekel-Bobrov, N., Posthuma D., Gilbert S.L., et al. (2007). The ongoing adaptive evolution of ASPM and Microcephalin is not explained by increased intelligence. Hum Mole Genet, 16, 600–8.

Montgomery, S.H. and N.I. Mundy. (2010). Brain Evolution : Microcephaly genes weigh in, Current Biology, 20(5), R244

Rejnmark L, Jørgensen ME, Pedersen MB, et al. (2004). Vitamin D insufficiency in Greenlanders on a Westernized fare: ethnic differences in calcitropic hormones between Greenlanders and Danes, Calcif Tissue Int, 74, 255-263.

Rimol, L.M., I. Agartz, S. Djurovic, A.A. Brown, J.C. Roddey, A.K. Kähler, M. Mattingsdal, L. Athanasiu, A.H. Joyner, N.J. Schork, et al. for the Alzheimer’s Disease Neuroimaging Initiative (2010). Sex-dependent association of common variants of microcephaly genes with brain structure. Proceedings of the National Academy of Science. USA, 107, 384–388.

Rushton, J.P., Vernon, PA.., Bons, T.A. (2007). No evidence that polymorphisms of brain regulator genes Microcephalin and ASPM are associated with general mental ability, head circumference or altruism. Biology Letters-UK, 3, 157–60.

Sellers EAC, Sharma A, Rodd C. (2003). Adaptation of Inuit children to a low-calcium diet, CMAJ, 168, 1141-1143.

Signorello, L.B., S.M. Williams, W. Zheng, J.R. Smith, J. Long, Q. Cai, M.K, Hargeaves, B.W. Hollis, and W.J. Blot. (2010). Blood vitamin D levels in relation to genetic estimation of African ancestry, Cancer Epidemiology, Biomarkers & Prevention, 19(9), 2325–2331.

Tuohimaa, P. (2009). Vitamin D and aging, Journal of Steroid Biochemistry and Molecular Biology, 114, 78-84.

Wang, J.K., Li, Y., and Su, B. (2008). A common SNP of MCPH1 is associated with cranial volume variation in Chinese population. Human Molecular Genetics, 17, 1329–1335.

Ask the rhino

Linda Vigilant – Was she in on the Big Secret? Was the rhino?

The HBD blogosphere has been rife with speculation about the reconstruction of the Neanderthal genome. John Hawks, Razib Khan, and Steve Sailer felt that something big was in the offing. Above all, this something would resurrect the multiregional model of human origins.

Much of the stir centered on a recent study by Sarah Joyce that showed a higher-than-expected amount of variability in the microsatellite DNA of modern humans. Since this DNA is unaffected by natural selection, the unexplained variability must have come from an outside source, i.e., Neanderthals and other archaic humans.

Then there was this comment:

Linda Vigilant, an anthropologist at the Planck Institute, found Joyce's talk a convincing answer to "subtle deviations" noticed in genetic variation in the Pacific region.

"This information is really helpful," says Vigilant. "And it's cool." (Dalton, 2010)

Linda Vigilant works at the Planck Institute, where a team headed by Svante Pääbo is reconstructing the Neanderthal genome. Perhaps she was privy to something big that Pääbo had discovered but was waiting to disclose.

Now the hand-wringing is over. This morning, it's been revealed that modern Europeans and Asians are 1-4% Neanderthal. Does this mean the multiregional model has been vindicated?

First, let’s be clear about what we mean by the multiregional model. Originally, it meant that Homo sapiens evolved out of earlier, more archaic humans at different times and at different places. Modern Europeans are thus primarily descended from Neanderthals, East Asians from Peking Man, and so on.

That version is now dead as a dodo. No one accepts it anymore. If we look at mtDNA or dental traits, the Neanderthals are no closer to modern Europeans than they are to modern Africans or modern East Asians (Krings et al., 1999; Ovchinnikov et al., 2000; Tyrrell & Chamberlain, 1998). In addition Joyce’s findings were not corroborated by Laval et al. (2010), who failed to find evidence of admixture in the noncoding DNA of modern Europeans and modern East Asians. The latest findings have backtracked a bit on this consensus, but not a lot.

So the current multiregional model is a weak version of the original. The idea now is that sporadic admixture brought potentially valuable Neanderthal alleles into our gene pool. Natural selection then caused the alleles to spread and multiply among modern humans. There could thus have been considerable Neanderthal introgression into our gene pool at certain loci, despite very low levels of admixture (Hawks & Cochran, 2006; Hawks et al., 2007). Laval et al. (2010) concede this point in their recent study:

However, it is important to emphasize that our inferences are based on non-coding neutral regions of the genome and that adaptive introgression from archaic to modern humans may have occurred to a greater extent. Indeed, in contrast to neutral alleles, adaptive variants may attain high frequencies by natural selection after minimal genetic introgression. Future studies comparing coding-sequence variation in modern humans and extinct hominids (e.g. Neanderthals) should help to answer this question. (Laval et al., 2010).

What do I think? This ‘minimal multiregionalism’ suffers from two arguments that seem to me weak:

1. Microbes do it. Why not humans?

Different strains of bacteria regularly swap genes, thus allowing new and better variants to leapfrog from one strain to another. Such ‘lateral gene transfer’ is a powerful engine of evolutionary change because it spares different species the trouble of having to reinvent the wheel.

But what works in simple organisms or for simple traits does not necessarily work elsewhere. Yes, if the gene works more or less independently, you can plug it into another genome and get the same result, like the pigment gene that aphids have somehow taken from fungi. But this kind of ‘plug and play’ is harder to pull off with complex traits in complex organisms, like humans. A particular gene might work like fresh sliced bread in one species … and like burnt toast in another.

But perhaps some adaptive solutions are still essentially the same in different complex organisms, like Neanderthals and modern humans. This point is made by Greg Cochran:

Selection often stalls out (in the medium term) because genetic variety has been exhausted, but an injection of archaic genes would have facilitated adaptive change. Moreover, some of those archaic alleles must have been useful ( i.e. had a fitness edge), since archaic humans in Eurasia had had a long time to adapt to their non-African ecology. (Khan, 2010)

Cochran and Hawks seem to be particularly interested in alleles relating to brain function, like the microcephalin allele that they had earlier attributed to gene transfer (Hawks & Cochran, 2006; Hawks et al., 2007). The Neanderthal microcephalin gene has since been reconstructed and … it does not have that allele (Hawks, 2009).

Yet Cochran and Hawks remain undeterred. One reason why they don’t see the weaknesses in their hypothesis is their unwillingness to spell it out in detail. Why won’t they? Well, ask the rhino.

As I understand it, their hypothesis is that Eurasian populations are relatively smart because their ancestors received special brain alleles from the Neanderthal gene pool. If I’m right in my understanding, they’re probably wrong in theirs. Modern humans adapted to temperate and arctic Eurasian environments in ways that were unique and unparalleled. Neanderthal brainpower had nothing to do with it. Although the Neanderthals apparently borrowed cultural and technological adaptations from modern humans, there is no evidence of any borrowing in the other direction. In fact, these archaic humans seem to have had very little to offer our ancestors:

Despite the apparent advances over their predecessors, Neanderthal technological complexity falls at the low end of the scale for recent hunter-gatherers. Both in terms of the number of types and component parts of individual implements, the complexity of Neanderthal tools and weapons is significantly lower than that of hunter-gatherers in northern latitudes (and more typical of modern groups in temperate or equatorial regions). Technological complexity in colder environments seems to reflect the need for greater foraging efficiency in settings where many resources are available only for limited periods of time. More specifically, the Neanderthals seem to have lacked untended facilities (e.g., traps and snares) and devices for food storage, which are common technological strategies for coping with resource fluctuations and high mobility requirements among hunter-gatherers in high latitudes. (Hoffecker, 2002, p. 135)

2. If Europeans were part-Neanderthal, they’d have native rights

This is an interesting argument: “If we Europeans are even a little bit Neanderthal, no one could deny our special claim to the European continent. People like Gordon Brown and Ségolène Royal would stop saying we’re no more indigenous than newly arrived immigrants.”

I have two responses. First, modern humans have inhabited Europe for some 35,000 years. If that length of residency doesn’t confer native rights, then no one anywhere has any—certainly not the Amerindians or the Inuit, who have been in the Americas for less than 15,000 years.

Which brings me to my second point. The currently dominant ideology—global capitalism—denies the very notion of native rights. It doesn’t matter whether your people have inhabited their land for 35,000 years or 35 million years. That’s just history, and we’ve come to the End of History. From now on, we’re all just individuals interacting in a global marketplace.

Eventually, this ideology will fall victim to its own contradictions. A market economy can exist with minimal state supervision only in a relatively homogeneous ‘high trust’ society. Liquidate that social environment, and you liquidate the economic environment that comes with it. At ‘best’, you’ll get a kind of totalitarian capitalism where everyone is deemed to be a potential thief or terrorist. At ‘worst’, the system will collapse, as communism did in Eastern Europe.

Of course, we shouldn’t wait passively for globalism to self-destruct. As thinking individuals with foresight, we should actively take part in the process. But such activism must start with an honest understanding of the world we live in. The lies of the current system cannot be fought with counter-lies. Europeans will not become more indigenous to their continent because they are found to have a few Neanderthal alleles here and there. They’re already indigenous, and that’s that.

Well, maybe the rhino can tell us more.

References

Dalton, R. (2010). Neanderthals may have interbred with humans. Genetic data points to ancient liaisons between species. Naturenews, April 20.
http://www.nature.com/news/2010/100420/full/news.2010.194.html

Hawks, J. (2010). Multiregional evolution lives! John Hawks Weblog, April 21, 2010.

http://johnhawks.net/weblog/reviews/evolution/introgression/joyce-dalton-interbreeding-2010.html

Hawks, J. (2009). The Neandertal genome FAQ, February 2009 edition, John Hawks Weblog, February 17, 2009.
http://johnhawks.net/weblog/reviews/neandertals/neandertal_dna/neandertal-genome-faq-2-2009.html

Hawks J., Cochran G., Harpending H.C., Lahn BT. (2007). A genetic legacy from archaic Homo. Trends Genet doi:10.1016/j.tig.2007.10.003

Hawks J., Cochran G. (2006). Dynamics of adaptive introgression from archaic to modern humans. PaleoAnthropology, 2006, 101-115. Open access

Hoffecker, J.F. (2002). Desolate Landscapes. Ice-Age Settlement in Eastern Europe. New Brunswick: Rutgers University Press.

Khan, R. (2010). Neandertal genomics paper coming? Discover magazine, April 27, 2010.
http://blogs.discovermagazine.com/gnxp/2010/04/neandertal-genomics-paper-coming/

Krings, M., Geisert, H., Schmitz, R.W., Krainitzki, H., & Pääbo, S. (1999). DNA sequence of the mitochondrial hypervariable region II from the Neandertal type specimen. Proceedings of the National Academy of Sciences USA, 96, 5581-5585.

Laval, G., E. Patin, L.B. Barreiro, and L-Quintana-Murci. (2010). Formulating a historical and demographic model of recent human evolution based on resequencing data from noncoding regions, PloS ONE 5(4) : e10284

Ovchinnikov, I.V., Götherström, A., Romanova, G.P., Kharitonov, V.M., Lidén, K., & Goodwin, W. (2000). Molecular analysis of Neanderthal DNA from the Northern Caucasus. Nature, 404, 490-493.

Sailer, S. (2010). The Neanderthal within. Steve Sailer’s iSteve Blog, May 2, 2010.
http://isteve.blogspot.com/2010/05/neanderthal-within.html

Tyrrell, A.J. & Chamberlain, A.T. (1998). Non-metric trait evidence for modern human affinities and the distinctiveness of Neanderthals. Journal of Human Evolution, 34, 549-554.