Wednesday, April 22, 2020

British hipsters

Why have British women become broader-hipped over the past three thousand years? (Wikicommons: Niek Sprakel)

British women have become broader-hipped over the past three thousand years or so. That's the conclusion of a recent study of alleles that influence female hip circumference, using data from the UKBiobank. 

Audrey Arner and her colleagues at Penn State identified 148 SNPs associated with female hip circumference and 49 SNPs associated with first child birth weight. Nine of them influence both women's hip circumference and first child birth weight. The SNPs associated with female hip circumference seemed to influence first child birth weight but not vice versa. There also seems to have been selection over approximately the last three thousand years for women with broader hips.

The baby's head is the biggest challenge during childbirth:

Human birthing is difficult owing to a tradeoff between large neonatal brain size and maternal pelvic dimensions, which are constrained by aspects of bipedal biomechanics. The net effect is that human neonatal head size closely matches maternal pelvic dimensions, unlike in our closest living relatives, the great apes, whose pelvic dimensions are larger than neonatal head sizes. (Franciscus 2009)

Have female hips become broader over the past three thousand years because the birth canal has had to accommodate babies with larger brains? That hypothesis would be consistent with an analysis of ancient DNA by Michael Woodley of Menie and others, who showed that alleles for educational attainment gradually increased in frequency between 4,560 and 1,210 years ago in Europeans and Central Asians. That increase may have been due to gene-culture coevolution: as societies grew larger and more complex, the average person had to perform mental tasks that likewise became larger in number and more complex. Such an environment would have favored the survival and reproduction of individuals with higher cognitive ability. Mean IQ thus rose over time, as did cranial capacity.

On the other hand, Henneberg (1988) showed that cranial capacity steadily shrank from the Mesolithic to modern times, becoming 9.9% smaller in men and 17.4% smaller in women. His conclusion was based on a large sample: 9,500 male skulls and 3,300 female skulls.

So we have a contradiction. Perhaps cranial capacity didn't really shrink from the Mesolithic to modern times. Perhaps smaller skulls are more likely to decompose faster. The skulls we unearth would therefore be a biased sample, and this bias toward preservation of larger skulls would gradually increase for skulls that have been in the ground longer.

The problem of "preservation bias" has already been noted with respect to female and infant remains:

There are nearly always more males than females in skeletal collections from archeological sites [...]. This has been explained in part by the comparatively rapid disintegration of lightly built female skeletons.

[...] The burial records show that most of the people buried in the Purisima cemetery were either infants, children, or elderly adults. The skeletal remains excavated from the cemetery, in contrast, are predominately those of young adults. The underrepresentation of young children in the skeletal collection is most likely a result of the comparatively rapid disintegration of their incompletely calcified bones.

[...] If, on the other hand, infants or elderly people are more common in a skeletal collection from a recent cemetery than they are in an ancient one, much less can be inferred about differences in the original age structure of the two burial populations. Such a difference would be expected due to differential preservation, even if the age structures of the two burial populations were identical. (Walker et al. 1988)

The same preservation bias might cause an overrepresentation of larger skulls among older remains.


Arner, A., H. Reyes-Centeno, G. Perry, and M. Grabowski. (2020). Pleiotropic effects on the recent evolution of human hip circumference and infant body size. The 89th Annual Meeting of the American Association of Physical Anthropologists (2020), April 17  

Franciscus, R.G. (2009). When did the modern human pattern of childbirth arise? New insights from an old Neandertal pelvis. Proceedings of the National Academy of Sciences 106(23): 9125-9126.  

Henneberg, M. (1988). Decrease of human skull size in the Holocene. Human Biology 60: 395-405.  

Walker, P.L., J.R. Johnson, and P.M. Lambert. (1988). Age and sex biases in the preservation of human skeletal remains. American Journal of Physical Anthropology 76: 183-188.

Woodley of Menie, M.A., S. Younuskunju, B. Balan, and D. Piffer. (2017). Holocene selection for variants associated with general cognitive ability: Comparing ancient and modern genomes. Twin Research and Human Genetics 20: 271-280. 

Tuesday, April 14, 2020

A second look at ASPM

Worldwide frequency of the new ASPM variant (Mekel-Bobrov et al. 2007)

Fifteen years ago, Science published a major finding: the human brain was still evolving well after the dawn of history. This could be seen in the evolution of ASPM, a gene that severely reduces brain size if it fails to function during development.

Here, we show that one genetic variant of ASPM in humans arose merely about 5800 years ago and has since swept to high frequency under strong positive selection. These findings, especially the remarkably young age of the positively selected variant, suggest that the human brain is still undergoing rapid adaptive evolution. (Mekel-Bobrov et al. 2007)

This variant seems to have come from the Middle East, where it is most prevalent today (37-52%). Its prevalence is next highest in Europe (38-50%). It is much less common in East Asia (0-25%) and virtually absent almost everywhere else.

Interest waned in the subject when several researchers found no association between the new variant and IQ scores or brain size (Mekel-Bobrov et al. 2007; Rushton et al. 2007). At the time it was widely thought, notably by J. Philippe Rushton, that IQ covers all aspects of mental effort. When I asked him whether the researchers had measured mental endurance, he replied: "No, they just used the standard IQ tests, head circumference, and (in our case) a test of altruism. [...] Generally there isn't thought to be much left to be explained after g is taken out."

This view has since been called into question. Some cognitive abilities correlate poorly with IQ, like executive function (Arffa 2007). Others show no correlation at all, like face recognition (Zhu et al. 2010). Furthermore, there has been growing evidence that the different ASPM variants of modern humans affect only some parts of the brain, and not the entire brain. According to a comparative study of primate species, the evolution of ASPM does not correlate with major changes in the whole brain or in cerebellum size: 

Particularly striking is the result that only major changes of cerebral cortex size and not major changes in whole brain or cerebellum size are associated with positive selection in ASPM. This is consistent with an expression report indicating that ASPM's expression is limited to the cerebral cortex of the brain (Bond et al. 2002). Our findings stand in contrast to recent null findings correlating ASPM genotypes with human brain size variation. Those studies used the relatively imprecise phenotypic trait of whole brain instead of cerebral cortex size (Rushton, Vernon, and Bons 2006; Woods et al. 2006; Thimpson et al. 2007). Although previous studies have shown that parts of the brain scale strongly with one another and especially with whole brain (e.g., Finlay and Darlington 1995), evidence here suggests that different brain parts still have their own evolutionary and functional differentiation with unique genetic bases. (Ali and Meier 2008)

Another comparative study found that ASPM had undergone accelerated change in chimpanzee, bonobo, and human lineages. Perhaps more interestingly, the effects were confined to development of the cerebral cortex:

Our findings indicate that ASPM variation is potentially associated with cerebral ventricular volume in chimpanzees, but not with any of the other brain structure measures. Ventricles are a critical site of neuronal proliferation in early development. Furthermore, the cerebrospinal fluid which circulates through the ventricles throughout life carries proteins that play important roles in central nervous system development and maintenance, like Sonic Hedgehog protein and Insulin-like Growth Factor 2.

Sonic Hedgehog protein?

Thus, variation in ventricular volume may affect the circulation of growth factors that could potentially influence the regulation of cerebral cortical development. Alternatively, because ASPM has a significant effect on neural progenitor cycling along the ventricles in fetal life, the association shown in our study may be a result of how brain size is patterned by ASPM during neurogenesis in early development. It has been shown that ASPM plays a role in regulating the affinity of ventricular radial glial cells (VRGs) for the ventricular surface. (Singh et al. 2019)

While there is also a broader role in brain development and brain size, it is usually limited to extreme cases, like microcephaly:

The abundance of ASPM mutations in human patients with microcephaly suggests that the gene plays a significant role in the regulation of brain size; however, variation in the gene has not always shown direct impact on brain circumference, volume, and intelligence in non-pathological populations. It is possible that ASPM interacts with other genes to affect brain volume, and thus associations depend on genetic background. Furthermore, selective pressure on ASPM may be associated with other aspects of neuronal function that do not lead to overt changes in brain structure, or might have a pleiotropic effect in other areas of the body, as ASPM is also expressed outside of the brain (Singh et al. 2019)

Possible explanations for the new ASPM variant

Shift from tonal to nontonal language?

So what made the new ASPM variant so successful? Two British researchers, Dan Dediu and D. Robert Ladd argue that it was a shift from tonal to non-tonal language. After showing that nontonality correlates geographically with the new ASPM variant (and also a new variant of the Microcephalin gene), they note that "the fact that nontonality is associated with the derived haplogroups suggests that tone is phylogenetically older and that the bias favors nontonality" (Dediu Ladd 2007).

If this is true, tonality gave way to nontonality in the Middle East when the new ASPM variant arose there some six thousand years ago. Yet we have no evidence of such a shift. Furthermore, languages have usually evolved from nontonality to tonality: "it seems to be the dominant view in the literature that tones arose from a toneless state" (Abramson 2004).

Spread of alphabetical writing?

I have argued for another explanation: the new ASPM variant was successful because it somehow assisted a mental task that originated in the Middle East some six thousand years ago and then spread into Europe. The task was alphabetical writing, specifically the mental process of transcribing speech and copying texts into alphabetical characters. Though more easily learned than ideographs, these characters place higher demands on the mind, 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 assigned to scribes of various sorts who enjoyed privileged status and probably superior reproductive success, thereby spreading the new ASPM variant throughout the population (Frost 2007).


For a brief time, over a decade ago, it seemed we had hard evidence that the human brain was still evolving during the time of recorded history. That evidence was soon rejected and largely forgotten, ironically through the efforts of J. Philippe Rushton. It didn't fit his model. As he saw it, if something fails to correlate with IQ, specifically with the g factor, it cannot be a cognitive ability and is unworthy of interest. 

Rushton was also held back by the idea that human evolution had largely ended with the end of the last ice age. Though intrigued by the contrary idea of ongoing human evolution, he never brought it into his theoretical work and generally treated it like an unwanted strip of film on a cutting-room floor.


Abramson, A.S. (2004). The plausibility of phonetic explanations of tonogenesis. In: Fant, G., Fujisaki, H., Cao, J., Xu, Y. (Eds.), From traditional phonology to modern speech processing: Festschrift for Professor Wu Zongji's 95th birthday. Beijing: Foreign Language Teaching and Research Press, 17-29.

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.

Arffa, S. (2007). The relationship of intelligence to executive function and non-executive function measures in a sample of average, above average, and gifted youth. Archives of Clinical Neuropsychology 22(8): 969-978 

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

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

Frost, P. (2008). Decoding the ASPM puzzle. Evo and Proud, August 27  

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  
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.

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. 

Singh, S.V., N. Staes, E.E. Guevara, S.J. Schapiro, J.J. Ely, et al. (2019). Evolution of ASPM coding variation in apes and associations with brain structure in chimpanzees. Genes, Brain and Behavior 18:e12582.

Zhang, J. (2003). Evolution of the Human ASPM Gene, a Major Determinant of Brain Size. Genetics 165(4): 2063-2070.

Zhu, Q., Y. Song, S. Hu, X. Li, M. Tian, Z. Zhen, Q. Dong, N. Kanwisher, and J. Liu. (2010). Heritability of the specific cognitive ability of face perception. Current Biology 20(2): 137-142. 

Tuesday, April 7, 2020

COVID-19 update

A dying man, stoned on suspicion of spreading the plague - Felix Jenewein, 1899 (Wikicommons)

SARS-CoV-2, though novel, belongs to a long-existing group of respiratory pathogens: coronaviruses. Until the first appearance of SARS in 2002, these pathogens did little harm to their hosts, usually causing nothing worse than a common cold. So they may have coevolved with us. Furthermore, this coevolution may have taken different forms in different human populations and different cultural environments.

Coronaviruses infect lung tissue via a receptor, ACE2, that varies structurally not only between Asians and other human groups but also between different Asian groups. In particular, the Chinese population has fewer alleles that code for weak binding to the coronavirus S-protein (Cao et al. 2020). Different ACE2 alleles are also associated with differences in susceptibility to diabetic retinopathy, an eye disease with a distinct global pattern of prevalence: 22% in Italy, 23% in China, 30% in the United Kingdom, and 40% in the United States (Adams 2020).

This geographic pattern doesn’t exist because some populations have become more resistant to coronaviruses. Instead, the reverse seems to have happened: some populations have become more susceptible to coronavirus infection, perhaps as a means to prevent more serious pulmonary infections, like tuberculosis and pneumonic plague (Shekhar et al. 2017). Such an effect has been shown with γherpesvirus 68 and cytomegalovirus (Barton et al. 2007; Miller et al. 2019). This crude vaccination boosts the immune response through increased production of IFN-γ and increased activation of macrophages.

Historically, tuberculosis was especially common in crowded environments, where people lived in proximity not only to each other but also to domesticated animals (Comas et al. 2013). Such environments have existed continuously for the longest time in China, as well as in areas like the Indo-Gangetic Plain, the Fertile Crescent, and the Mediterranean Basin. Those areas are where people should be most susceptible to coronavirus infection.

This may explain why COVID-19 has been more severe in southern Europe than in northern Europe. It is surprising that infection tends to become less severe with latitude when one would expect the opposite: respiratory viruses spread more effectively under conditions of lower temperature, lower humidity, and lower solar UV.

Ongoing research?

These geographic differences have caught the interest of a molecular epidemiologist at the University of Hawai'i, Maarit Tiirikainen:

"There have been major differences in the rates of SARS-CoV-2 infection and the severe disease between the different geographic regions since the beginning of the COVID-19 pandemic, even among young individuals," Dr. Tiirikainen said. "Epidemiological studies-so-called Genome Wide Association Studies (GWAS)-indicate that populations carry different variants of the ACE2 gene. This variation in the gene coding for the ACE2 receptor may have an effect on the number of ACE2 receptors on the lung cells, as well as on how effectively the virus binds to the receptor. There may also be genetic differences in immune and other important genes explaining why some people get more sick than others."

She is collaborating with a genomics company, LifeDNA, in a study that will initially focus on Hawai'i's multiethnic inhabitants, specifically their diversity of ACE2 alleles in relation to the latest coronavirus (LifeDNA 2020 – h/t to Steve Sailer).

Parting thoughts

All humans can get infected by coronaviruses, but the infection tends to vary in severity from one population to another. This variance may reflect differences in genetic adaptation in different cultural environments.

Of course, adaptation may also be cultural. Because natural selection acts on the end result, and not on the means to that end, the means may be a purely learned algorithm, like adding spices to food or avoiding physical contact with strangers. One might not have understood why or how such practices worked, but they did work and would be passed on to subsequent generations, thus becoming the traditional way of doing things. Today, we’re likely to reject such practices as outmoded superstitions.

So be modern. Hug a stranger.


Adams N. (2020). Cracking the code to the 2019 novel coronavirus (COVID-19): Lessons from the eye. Eye Reports 6(1).

Barton E.S., White D.W., Cathelyn J.S., Brett-McClellan K.A., Engle M., Diamond M.S., et al. (2007). Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 447: 326-329.

Cao Y., Li L., Feng Z., Wan S., Huang P., Sun X., et al. (2020). Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discovery 6(11). 

Comas I., Coscolla M., Luo T., Borrell S., Holt K.E., Kato-Maeda M., et al. (2013). Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans. Nature Genetics 45(10): 1176-1182.

LifeDNA (2020). COVID-19: LifeDNA and University of Hawai’i Collaborate on Studying Why Certain Populations Are Hit Harder. Research focuses on ACE2 receptor, probing the role of genetics in both susceptibility to infection and severity of response April 2, University of Hawai'i Cancer Center

Miller H.E., Johnson K.E., Tarakanova V.L., Robinson R.T. (2019). γ-herpesvirus latency attenuates Mycobacterium tuberculosis infection in mice. Tuberculosis 116: 56-60.

Shekhar S., Schenck K., Petersen F.C. (2017). Exploring host-commensal interactions in the respiratory tract. Frontiers in Immunology 8: 1971.