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.


painlord2k@gmail.com said...


Sonic hedgehog is a protein that in humans is encoded by the SHH gene.[5] It is the best studied ligand of the hedgehog signaling pathway, others being desert hedgehog (DHH) and Indian hedgehog (IHH). It plays a key role in the development of animals, from insects to mammals. In vertebrates, it is involved in organogenesis, including the growth of digits on limbs and the organization of the brain. Sonic hedgehog is an archetypal example of a morphogen as defined by Lewis Wolpert's French flag model—a molecule that diffuses to form a concentration gradient and has different effects on the cells of the developing embryo depending on its concentration. Sonic hedgehog is also active in adults; for example, it controls the proliferation of adult stem cells and has been implicated in the development of some cancers.

Peter Frost said...

Thanks! I was wondering whether that was some kind of practical joke.

Anonymous said...

Interesting thought. Our ability to read at all is quite fascinating. One of my children has severe dyslexia. She's smart--she scored very well on the IQ test they gave her at school--but letters just don't *click* for her. In her case, it's clearly not an intelligence issue so much as not being optimized to do a specific task.