This is where the virus is least deadly

Patterson Town Hall, (Wikicommons - Anthony22). Putnam County NY has the lowest IFR for COVID-19 in the United States.



SARS-CoV-2 is more virulent in southern Europe than in northern Europe. The reason, I’ve argued, is that the Mediterranean Basin is one of several regions where humans have coevolved for a longer time with crowded social environments. By "crowded" I mean not only proximity to other people but also proximity to domesticated animals. In such environments, which are prone to deadly pulmonary diseases like tuberculosis and pneumonia, natural selection may have favored susceptibility to infection by coronaviruses, which are normally mild in their effects, as a means to maintain a strong immune response to respiratory infections (Frost 2020). 

If we look at case fatality rates, Italy and Spain have been hit much worse than Germany, Switzerland, Austria, and Iceland. The United Kingdom falls between the two extremes, although a confounding factor is its large population of non-native origin (Singh 2020).

This pattern also shows up in a meta-study of infection fatality rates. Meyerowitz-Katz and Merone (2020) examined thirteen estimates of IFR from a wide range of countries. They came to two main conclusions:

- Mean IFR is 0.75% but varies considerably between countries;

- IFR has increased over time, being lower in February and March than in April and May.

Earlier estimates were based on the assumption that the average time lag between infection and death is two weeks on average. Actually, it's probably longer, perhaps a month. Later deaths may have thus been missed by estimates made in February and March.

If we look only at IFRs from April and May, the meta-study shows a north-south cline in the virulence of SARS-CoV-2:

Germany - 0.36%
France - 0.70%, 0.80%
Italy - 0.95%, 1.29%, 1.60%

For the same time period, the meta-study also presented three estimates from the United States:

New York City - 0.93%
California - 0.20%
United States - 1.30%

The last study provides estimates ranging from a low of 0.5% in Putnam County NY to a high of 3.6% in King County WA (Basu 2020). These numbers are so high because IFR is calculated only in relation to symptomatic cases. In my opinion, this study is not comparable to the others and should not have been included in the metastudy. It is nonetheless useful for charting the virulence of SARS-CoV-2 within the United States.

So why would the virus be less virulent in Putnam County NY than in King County WA? Let's consider the demographics in each case. The first county is 80% non-Hispanic White, 14% Hispanic, 3% Black, and 2% Asian. The second county is 65% non-Hispanic White, 15% Asian, 9% Hispanic, and 6% Black. Putnam County is whiter and probably less cosmopolitan than King County, which encompasses the Seattle area. This impression is strengthened by the voting pattern in Putnam County, which trends much more Republican than Democrat (Wikipedia 2020). The virus thus seems to be least virulent among "old stock" Euro Americans. I would also predict low virulence in Amerindian communities.

Virulence may also differ between west coast Hispanics and east coast Hispanics, as suggested by the difference between California and New York City. East Coast Hispanics are less often Mexican and more often Puerto Rican. They may thus be more vulnerable because they are more Mediterranean and less Amerindian by ancestry.


References

Basu, A. (2020). Estimating The Infection Fatality Rate Among Symptomatic COVID-19 Cases In The United States. Health affairs (Project Hope). 2020:101377hlthaff202000455.
https://www.healthaffairs.org/doi/full/10.1377/hlthaff.2020.00455

Frost, P. (2020). Does a commensal relationship exist between coronaviruses and some human populations? Journal of Molecular Genetics 3(2): 1-2.
https://researchopenworld.com/does-a-commensal-relationship-exist-between-coronaviruses-and-some-human-populations/

Meyerowitz-Katz, G. and L. Merone. (2020).  A systematic review and meta-analysis of published research data on COVID-19 infection-fatality rates.  medRxiv, May 18, 2020
https://www.medrxiv.org/content/10.1101/2020.05.03.20089854v2 

Singh, S. (2020). BCG vaccines may not reduce COVID-19 mortality rates. medRxiv April 11, 2020 
https://www.medrxiv.org/content/10.1101/2020.04.11.20062232v1

Wikipedia (2020). Putnam County, New York.
https://en.wikipedia.org/wiki/Putnam_County,_New_York 

Does a commensal relationship exist between coronaviruses and some human populations?

Nanjing Road, Shanghai (Wikicommons - Stephen Codrington). Populations with a long history of social crowding may have become more susceptible to coronavirus infection.


I've published a paper on coevolution between coronaviruses and "crowded" social environments. Comments are welcome. Here is the abstract:


Coronaviruses enter lung tissue via the ACE2 receptor, which varies structurally among human populations. In particular, the Chinese population has fewer variants that bind weakly to the coronavirus S-protein. This global variation suggests that the ACE2 receptor has coevolved with different environments, some of which have favored susceptibility to infection of lung tissue by coronaviruses. 

It has been argued that respiratory viruses boost the immune response of lung tissue and thereby prevent more serious pulmonary diseases, like tuberculosis, pneumonia, and pneumonic plague. This preventive effect has been shown with other viral pathogens, notably γherpesvirus 68 and cytomegalovirus. Some human populations may have therefore gained protection from severe respiratory infections by becoming more susceptible to mild respiratory infections, such as those normally caused by coronaviruses. 

This commensal virus-host relationship would have been especially adaptive wherever respiratory pathogens could easily propagate, i.e., in crowded environments, where many people live in proximity not only to each other but also to animal sources of infection. In regions that have long had crowded environments, natural selection may have favored susceptibility to infection by coronaviruses, which are normally mild in their effects, as a means to maintain a strong immune response to deadly pulmonary diseases.


Reference

Frost, P. (2020c). Does a commensal relationship exist between coronaviruses and some human populations? Journal of Molecular Genetics 3(2): 1-2.
https://researchopenworld.com/does-a-commensal-relationship-exist-between-coronaviruses-and-some-human-populations/   

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.


References

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
https://meeting.physanth.org/program/2020/session26/arner-2020-pleiotropic-effects-on-the-recent-evolution-of-human-hip-circumference-and-infant-body-size.html  

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.
https://www.pnas.org/content/106/23/9125.short  

Henneberg, M. (1988). Decrease of human skull size in the Holocene. Human Biology 60: 395-405.
https://www.jstor.org/stable/41464021  

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.
https://onlinelibrary.wiley.com/doi/abs/10.1002/ajpa.1330760206

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.
https://www.cambridge.org/core/journals/twin-research-and-human-genetics/article/holocene-selection-for-variants-associated-with-general-cognitive-ability-comparing-ancient-and-modern-genomes/BF2A35F0D4F565757875287E59A1F534 

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).


Conclusion

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.


References

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.
http://www.haskins.yale.edu/Reprints/HL1336.pdf

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.
http://www.haskins.yale.edu/Reprints/HL1336.pdf

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
https://academic.oup.com/acn/article/22/8/969/3025 

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

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. (2008). Decoding the ASPM puzzle. Evo and Proud, August 27
http://evoandproud.blogspot.com/2008/08/decoding-aspm-puzzle.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

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 

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.
https://dukespace.lib.duke.edu/dspace/bitstream/handle/10161/19252/Singh_etal2019.pdf?sequence=2

Zhang, J. (2003). Evolution of the Human ASPM Gene, a Major Determinant of Brain Size. Genetics 165(4): 2063-2070.
https://www.genetics.org/content/165/4/2063.short

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.
https://www.sciencedirect.com/science/article/pii/S096098220902123X 

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.


References

Adams N. (2020). Cracking the code to the 2019 novel coronavirus (COVID-19): Lessons from the eye. Eye Reports 6(1). 
https://eyereports.org/index.php/eyereports/article/view/97

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. 
https://www.nature.com/articles/nature05762

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). 
https://www.nature.com/articles/s41421-020-0147-1%3C/blockquote%3E 

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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800747/

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 
https://www.uhcancercenter.org/about-us/newsroom/600-covid-19-lifedna-and-university-of-hawai-i-collaborate-on-studying-why-certain-populations-are-hit-harder

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. 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876742/

Shekhar S., Schenck K., Petersen F.C. (2017). Exploring host-commensal interactions in the respiratory tract. Frontiers in Immunology 8: 1971. 
https://www.frontiersin.org/articles/10.3389/fimmu.2017.01971/full

Affective empathy: a double-edged sword

March in Brooklyn (?) (Wikicommons - Amanda Hirsch). Can we learn to feel another person's pain or joy? Twin studies indicate that affective empathy is 52-57% heritable. The rest includes prenatal and postnatal influences that happen long before social learning begins.



In our species, a major problem has been to create high-trust societies that encompass large numbers of people who are not closely related and yet have to deal with each other regularly. This problem hasn’t been resolved in most human populations—for the most part, people trust only family and close kin. Consequently, a market economy cannot realize its full potential: a lot of economic activity never happens because the low level of trust makes it too costly. This point is repeatedly made in the book India Unbound by Gurcharan Das:

[…] the social life of Indians revolves around the family or caste. It does not encompass the whole community. Perhaps this is why our streets are dirty when our homes are spotlessly clean. (Das 2002, p. 81)

A striking characteristic of Indian business is that it is family-owned and family-managed. […] (Das 2002, p. 265)

Whether businesses here can create managerial capitalism depends partly on Indian society’s ability to build “social capital.” Where strangers spontaneously trust each other and cooperate with each other, there is high social capital. Indeed, Tocqueville regarded this “art of association” as an essential virtue of American society because it moderated the American tendency toward individualism. Trust and cooperation are necessary in all market activity. Social capital can help companies make the transition from small family units to large, professionally run enterprises. High trust can dramatically lower transaction costs, corruption, and bureaucracy. (Das 2002, pp. 267-268)

The "large society problem" has been fully resolved only in two culture areas: Northwest Europe and East Asia. In general, the solution has been to weaken the importance of kinship in social relations and to strengthen impersonal forms of sociality that can bring everyone together, and not just closely related people. To be specific, the focus of empathy has been extended beyond the circle of close kin, and people become more attuned to universal social rules that exist independently of kinship obligations.

Northwest Europeans have transcended the ties of kinship to an unusual extent. North and west of a line running from Trieste to St. Petersburg, kinship ties have been relatively weak for at least a millennium. Almost everyone is single for at least part of adulthood, and many stay single their entire lives. In addition, households often have non-kin members, and children normally leave the nuclear family to form new households. This weak-kinship environment is associated with an equally unusual pattern of behavior: greater individualism, less loyalty to kin, and more willingness to trust strangers.

This is not so with East Asians, who still have strong kinship ties and are actually less individualistic than humans in general. Whereas a greater sense of self has helped Northwest Europeans transcend the limitations of kinship to build larger societies, East Asians have relied on a lesser sense of self to strengthen impersonal sociality within and beyond their circle of close kin. There is more emphasis on holistic attention, on social happiness rather than personal happiness, and on suspension of self-interest. Conversely, there is less emphasis on self-expression, self-esteem, and self-efficacy (Kitayama et al. 2014).


Empathy: cognitive versus affective

Empathy seems especially key to strengthening social relations beyond one's circle of close kin. It has two components. Cognitive empathy is the ability to understand the feelings of another person, and affective (or emotional) empathy is the ability to internalize those feelings and actually feel that person's pain or joy. Affective empathy is 52-57% heritable, and cognitive empathy 27% heritable (Melchers et al. 2016). This is in line with longitudinal studies on children: affective empathy remains stable as a child develops, while cognitive empathy progressively increases, perhaps through learning (Decety et al. 2017). 

Affective empathy, but not cognitive empathy, is sexually dimorphic: 

[...] females do indeed appear to be more empathic than males [but] [t]hey do not appear to be more adept at assessing another person's affective, cognitive, or spatial perspective" (Hoffman 1977).

Women are faster in recognizing facial expression, emotional body language, more sensitive to baby voice, more experientially reactive to negative, but not positive, emotional pictures compared to men. Men, on the other hand, seem to show better skills in cognitive empathy while women performed better in emotional empathy (Uysal et al. 2020).

This difference between men and women has been confirmed by a British study (Baron-Cohen and Wheelwright 2004), a largely Argentinean study (Baez et al. 2017), an Italian twin study (Toccaceli et al. 2018), and a Chinese study (Liu et al. 2018). The size of the difference varies, however, being slight in the British and Argentinean studies, large but not significant in the Italian study, and significant in the Chinese study. The sex difference in affective empathy largely accounts for the sex difference in aggression (Dryburgh and Vachon 2019). Women are also more likely to forgive, and this sex difference seems mediated by the sex difference in empathy (Witvliet et al. 2020).

Thus, affective empathy may have initially served to facilitate the relationship between a mother and her young children. This female adaptation may have a long evolutionary history among mammals: it has been shown that sensitivity to the pain of others is stronger in female mice than in male mice (Uysal et al. 2018).

As some human populations formed larger and more complex societies, natural selection may have gradually extended affective empathy to both sexes and to all social relationships. An analogy would be the gene-culture coevolution between lactose metabolism and dairy farming. The ability to digest lactose is lost after infancy by most humans but is lifelong in cultures where adults consume milk and other dairy products.


Northwest Europeans versus East Asians

Northwest Europeans and East Asians are similar in having high levels of empathy but differ in the relative importance of cognitive empathy versus affective empathy. Affective empathy is much more key to prosocial behavior among Northwest Europeans than among East Asians. This was the conclusion of Li et al. (2019):

Previous research has shown that affective empathy, rather than cognitive empathy, significantly predicts people's altruistic sharing behavior in economic games. However, most of these studies were conducted in Western populations. There might be cultural differences in the relations between empathy and altruism due to different levels of empathy between Western and Asian individuals. In this study, we measured different aspects of empathy in Chinese adults as well as their allocation offers in the dictator and ultimatum games. We found that cognitive empathy, but not affective empathy, was a significant predictor of adults' altruistic sharing behavior in the two economic games.

Similarly, Siu and Shek (2005) found that Chinese subjects had trouble distinguishing between cognitive empathy and affective empathy. They concluded that "Chinese people might not perceive the items from the two dimensions as too different in nature."

One might think that cognitive empathy would be worse than affective empathy as a basis for prosocial behavior. For instance, sociopaths are usually high in cognitive empathy: they know how another person feels in a given situation, but they use this knowledge to exploit and control that person. Wouldn't their resulting success eventually destroy social order? East Asian societies may have avoided this outcome through their low level of individualism and their correspondingly high level of social conformity. Kitayama et al. (2014) makes this point when discussing certain alleles of a gene, DRD4, that are associated with risk seeking and heavy drinking in the United States but not in East Asia. These alleles seem to increase the desire to emulate one's peers, and such emulation is more likely to favor dysfunctional behavior in the United States than in East Asia:

It might be the case that the 7R and 2R alleles are associated with greater acquisition of culturally sanctioned social orientations under generally favorable conditions of socialization, such as careful guidance and scaffolding of norm-congruous behaviors by socialization agents (e.g., parents, relatives, neighbors), but with markedly different, deviant behaviors (e.g., delinquency and risk proneness) under unfavorable social conditions or adversity, which might "reward" externalization or risk taking. (Kitayama et al. 2014)

These alleles seem to explain the weaker individualism and stronger social conformity of East Asians. When Kitayama et al. (2014) compared a sample of Euro-Americans with a sample of East Asians born in China, Korea, or Japan, they found that the East Asians were less individualistic than the Euro-Americans on a social orientation test, but this difference was limited to carriers of DRD4 alleles that increase dopamine signalling, i.e., 7- or 2-repeat alleles. Non-carrier East Asians were just as individualistic as non-carrier Euro-Americans (Kitayama et al. 2014)

Finally, we should keep in mind a serious shortcoming of affective empathy: you may become so overcome by your emotion that you can no longer accurately assess the target of your empathy. This point is made by Atkins (2014) in a review of several experimental studies of empathy in British and East Asian subjects:

Thus, it is possible that being in a highly emotionally empathic state may cloud the ability to accurately infer the emotions of a target due to the heightened emotions experienced in response to the suffering of another. In line with this reasoning, East Asians' lower level of emotional involvement might have freed cognitive resources to allow them to more accurately infer the emotions of targets.

A review of the subject

Atkins (2014) comes to several conclusions in his comparative review:

- When viewing a person suffering physical pain, British subjects report greater negative affect than do East Asian subjects.

-  When viewing a person suffering social pain, British subjects show greater empathic concern but lower empathic accuracy than do East Asian subjects.

- British subjects report greater empathic concern, but lower empathic accuracy than do Chinese subjects. Emotional expressivity predicts British but not Chinese empathic concern.

- Empathic concern explains differences between the two groups in donating, a measure of prosocial behavior.

- American subjects, more so than Japanese subjects, feel more affective empathy for one friend over another when the two friends are engaged in an intense disagreement.

In sum, East Asians have resolved the "large society problem" through a different psychological and behavioral package that places less emphasis on emotional involvement and more on restoration of social harmony.


References

Atkins, D. (2014). The Role of Culture in Empathy: The Consequences and Explanations of Cultural Differences in Empathy at the Affective and Cognitive Levels. Doctor of Philosophy (PhD) thesis, University of Kent.
https://kar.kent.ac.uk/47970/  

Baez, S., Flichtentrei, D., Prats, M., Mastandueno, R., García, A.M., Cetkovich, M., et al. (2017). Men, women...who cares? A population-based study on sex differences and gender roles in empathy and moral cognition. PLoS ONE 12(6): e0179336.
https://journals.plos.org/plosone/article/file?type=printable&id=10.1371/journal.pone.0179336  

Baron-Cohen, S. (2011). The Empathy Bell Curve. Phi Kappa Phi Forum; Baton Rouge 91(1): 10-12.
http://go.galegroup.com/ps/anonymous?id=GALE%7CA267422895&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=15385914&p=AONE&sw=w  

Das, G. (2002). India Unbound. The Social and Economic Revolution from Independence to the Global Information Age. New York: Anchor Books.

Decety, J., K.L. Meidenbauer, and J.M. Cowell. (2017). The development of cognitive empathy and concern in preschool children: A behavioral neuroscience investigation. Developmental Science 2018;21:e12570. 
https://doi.org/10.1111/desc.12570  

Dryburgh, N.S.J., and D.D. Vachon. (2019). Relating sex differences in aggression to three forms of empathy. Personality and Individual Differences 151(1): 109526.
https://e-tarjome.com/storage/panel/fileuploads/2019-08-25/1566713640_E12864-e-tarjome.pdf 

Frost, P. (2017). The Hajnal line and gene-culture coevolution in northwest Europe. Advances in Anthropology 7: 154-174.
https://www.scirp.org/html/3-1590616_78813.htm  

Frost, P. (2015). Two paths. The Unz Review, January 24
https://www.unz.com/pfrost/two-paths/  

Hajnal, J. (1965). European marriage patterns in perspective: essays in historical demography. In D.V. Glass and D.E. Eversley (eds). Population in History. Chicago: Aldine Publishing, pp. 101-143.
https://www.taylorfrancis.com/books/e/9781315127019/chapters/10.4324/9781315127019-7  

Hallam, H.E. (1985). Age at first marriage and age at death in the Lincolnshire Fenland, 1252-1478. Population Studies 39(1): 55-69.
https://www.tandfonline.com/doi/abs/10.1080/0032472031000141276  

hbd chick (2014). Big summary post on the Hajnal Line. October 3
https://hbdchick.wordpress.com/2014/03/10/big-summary-post-on-the-hajnal-line/

ICA (2013). Research Themes - Marriage Patterns, Institutions for Collective Action
http://www.collective-action.info/_THE_MarriagePatterns_EMP  

Hoffman, M. L. (1977). Sex differences in empathy and related behaviors. Psychological Bulletin 84(4): 712-722. 
http://dx.doi.org/10.1037/0033-2909.84.4.712   

Kitayama, S., A. King, C. Yoon, S. Tompson, S. Huff, and I. Liberzon. (2014). The Dopamine D4 Receptor Gene (DRD4) Moderates Cultural Difference in Independent Versus Interdependent Social Orientation. Psychological Science 25: 1169-1177. http://pss.sagepub.com/content/25/6/1169.short 

Li, Z., J. Yu, and L. Zhu. (2019). Associations between empathy and altruistic sharing behavior in Chinese adults. The Journal of General Psychology 146(1): 1-16
https://www.tandfonline.com/doi/abs/10.1080/00221309.2018.1510826  

Liu, J., X. Qiao, F. Dong, and A. Raine. (2018). The Chinese version of the cognitive, affective, and somatic empathy scale for children: Validation, gender invariance and associated factors. PLoS ONE 13(5): e0195268. 
https://doi.org/10.1371/journal.pone.0195268 

Melchers, M., C. Montag, M. Reuter, F.M. Spinath, and E. Hahn. (2016). How heritable is empathy? Differential effects of measurement and subcomponents. Motivation and Emotion 40(5): 720-730. 
https://doi.org/10.1007/s11031-016-9573-7

Schulz, J.F., D. Bahrami-Rad, J.P. Beauchamp, and J. Henrich. (2019). The Church, intensive kinship, and global psychological variation. Science 366(707): 1-12. 
https://coevolution.fas.harvard.edu/files/culture_cognition_coevol_lab/files/sciencefull.pdf

Seccombe, W. (1992). A Millennium of Family Change. Feudalism to Capitalism in Northwestern Europe. London: Verso.
https://books.google.ca/books?id=MiTxtZI-pzUC&printsec=frontcover&hl=fr&source=gbs_ge_summary_r&cad=0#v=onepage&q&f=false

Siu, A.M.H. and D.T. L. Shek. (2005). Validation of the Interpersonal Reactivity Index in a Chinese Context. Research on Social Work Practice 15: 118-126.
http://rsw.sagepub.com/content/15/2/118.short  

Toccaceli, V., C. Fagnani, N. Eisenberg, G. Alessandri, A. Vitale and M.A. Stazi. (2018). Adult Empathy: Possible Gender Differences in Gene-Environment Architecture for Cognitive and Emotional Components in a Large Italian Twin Sample. Twin Research and Human Genetics 21(3): 214-226
https://doi.org/10.1017/thg.2018.19   

Uysal, N., U.M. Çamsari, M. ATEs, S. KandIs, A. Karakiliç, and G.B. Çamsari (2019). Empathy as a Concept from Bench to Bedside: A Translational Challenge. Noro psikiyatri arsivi, 57(1): 71-77. https://doi.org/10.29399/npa.23457 

Witvliet, C.V., L. M.R. Luna, J.L. VanderStoep, T. Gonzalez, and G.D. Griffin (2020). Granting forgiveness: State and trait evidence for genetic and gender indirect effects through empathy. The Journal of Positive Psychology 15(3): 390-399 
https://www.tandfonline.com/doi/full/10.1080/17439760.2019.1615108 

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.


Conclusion

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:

https://www.amren.com/features/2020/03/how-did-whites-get-their-appearance/ 
https://www.amren.com/features/2020/03/why-are-human-groups-so-different/

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

http://www.evopsy.com/concepts/coevolution-frost.html
http://www.evopsy.com/concepts/hbd-frost.html


References

Bae, B-I., D. Jayaraman, and C.A. Walsh. (2015). Genetic changes shaping the human brain. Developmental Cell 32: 423-434. 
https://www.sciencedirect.com/science/article/pii/S1534580715000787

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. 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817182/

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.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493026/

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.
http://roceeh.mediatis.de/fileadmin/download/Publications/Bramanti_Sci09_Meso_Neo.pdf

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. 
https://www.sciencedirect.com/science/article/pii/S0002929707603085

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.
https://www.sciencedirect.com/science/article/pii/S0960982216315421

King, M-C, and A.C. Wilson. (1975). Evolution at two levels in humans and chimpanzees. Science 188: 107-116.
http://hydrodictyon.eeb.uconn.edu/people/schwenk/KingWilsonHumansChimps75.pdf

Majid, A., and N. Kruspe. (2018). Hunter-gatherer olfaction is special. Current Biology 28: R108-R110. 
https://www.sciencedirect.com/science/article/pii/S0960982217316160

Melchior, L., N. Lynnerup, H.R. Siegismund, T. Kivisild, and J. Dissing. (2010). Genetic diversity among ancient Nordic populations. PLoS One 5(7): e11898
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912848/

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.
http://cnc.cj.uc.pt/BEB/private/pdfs/2007-2008/RepBiology/ExtraBibliog/MontielSosa2006.pdf

The ENCODE Project Consortium. (2012). An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57-74 
https://www.nature.com/articles/nature11247

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.
https://books.google.ca/books?id=mfANqS-SnwgC&printsec=frontcover&hl=fr&source=gbs_ge_summary_r&cad=0#v=onepage&q&f=false