Q&A for History of Mankind (34)

Latest tricks to survive altitude sickness for life, in New Guinea and the Himalayas. Plus, questions about Hannibal, India, resistance vs slavery & Sertorius, Roman King of Spain.

To check all previous newsletters in the History of Mankind, which is pretty long, you can click here.

This is the thirty-fourth Q&A for History of Mankind. Paying subscribers received an email asking for questions; and those are right below the paywall.

Here’s the regular reminder, first of all: all new paying subscribers get an electronic copy of my 2023 book ”Emperor Whisperers: a comparative history of ancient Western and Chinese philosophy” (also available here) and also one of “Gods & Heroes,” an updated compilation of the first 43 posts in the History of Mankind series. So, if you are paying subscriber and you didn’t get both already, please let me know.

Before we get to the questions, there’s also a couple of fascinating papers I’d like to share with you guys and gals. The titles sound a little dry (you know academics are not known for their catchy titles) but they both have pretty interesting implications.

The first paper is “Genetic Signatures of Positive Selection in Human Populations Adapted to High Altitude in Papua New Guinea,” by Ram González-Buenfil et al (Genome Biology and Evolution, Volume 16, Issue 8, August 2024). This one looks at the way tribesmen from Papua New Guinea evolved to cope with altitude sickness and survive and breed where most humans can’t.

This is a topic dear to my heart, because it’s a great way to explain how genetic evolution among humans hasn’t stopped and will never stop, and how different populations across the planet keep evolving separate genetic approaches to common problems, through the old, true-and-tested system of sexual selection.

I first discussed the issue of genetic evolution against altitude sickness in Chinese Kings & Alcohol-Filled Pools, looking at the development of the earliest attested Tibetan populations in the highlands of modern Sichuan, China:

The Hengduan Mountains, an impressive range just to the west of the Sichuan plateau, was another key geographic marker – then as now – as it represented the eastern-most point where ethnic Tibetans with specific genetic adaptations for high-altitude-living accounted for a majority of the population; it may have also been the place through which cold-tolerant barley agriculture, based on Yellow River strains, expanded to Tibet proper around 1600 BC, together with millet farming techniques, making a huge impact on demographic expansion in Tibet.

Like I explained then, David Epstein, in “The Sports Gene: Inside the Science of Extraordinary Athletic Performance” (2013), notes that high-altitudes adaptations across continents have been surprisingly different:

From the 20^th century AD, Kenya and Ethiopia’s long-distance runners thrived on their altitude-adapted genes, but people living in the different Andean and Himalayan climates – both not fostering a narrow body type – had different genetic adaptations. Native Andeans have profuse portions of red blood cells and, within them, oxygen-carrying hemoglobin; they in fact have so much hemoglobin that their blood can become viscous and unable to circulate well, and some Andeans develop chronic mountain sickness. Tibetans, however, have normal, sea-level hemoglobin values, and low oxygen saturation, lower than people at sea level. Most Tibetans have a special version of a gene, EPAS1, that acts as a gauge, sensing the available oxygen and regulating the production of red blood cells so that the blood does not become dangerously thick. But it also means Tibetans don’t have the increase in oxygen-carrying hemoglobin that Andeans do; they survive by having extremely high levels of nitric oxide in their blood. Nitric oxide cues blood vessels in the lungs to relax and widen for blood flow: 240 times as much nitric oxide in the blood as White Europeans, so they adapted to having very high blood flow in their lungs, and to breathe deeper and faster than native lowlanders, as if they’re in a constant state of hyperventilation. Ethiopians, and specifically the Amhara ethnic group living along the Rift Valley, have normal, sea-level allotments of hemoglobin and normal, sea-level oxygen saturation: their own trick is moving oxygen unusually rapidly from the tiny air sacs in their lungs into their blood.

Not so long ago, in the Q&A of April last year, I discussed a recent paper arguing that high-altitude Andean human groups experienced pervasive selective events driving the formation of extra blood vessels, which resemble those previously attested for Himalayan populations, although they were concentrated on much shorter time spans.

This is probably the reason why Andean populations took longer to settle high-altitude regions like those around Lake Titicaca, and they still need products like coca leaves to avoid high-altitude sickness. Keep in mind that Tibetans don’t appear to require any extra products or precautions when traveling across their land; and neither do Papuans, it appears.

In their own paper, González-Buenfil et al explain that alleles found in Papuan highlanders living in two separate “ecoregions” enhance the expression of Lactate dehydrogenase A (LDHA), an enzyme which in humans is encoded by the LDHA gene. This facilitates a transition from oxidative to glycolytic metabolism – a metabolic pathway that converts glucose into energy – during periods of hypoxia (low oxygen levels), by flooding the body with increased levels of the enzyme, in a process that is pretty similar to the separate Tibetan adaptation to high altitude.

Most intriguingly, they suggest that Papuans may rely for this on alleles inherited from Denisovan populations with whom they mixed very intensely: Papuans have a history of genetic admixture with archaic hominins, exhibiting some of the highest proportions of Denisovan ancestry, of around 4%. And you know who else have a relatively high level of Denisovan ancestry? Exactly, the Tibetans. And they add:

While the observed selection signatures in Papua New Guinea predominantly suggest distinct selective pressures across the two ecoregions, we also identified shared selection signals between the two. These shared signals, rather than pointing to a single set of functional implications, span a diverse array of biological processes. This complexity highlights the need for further investigation to fully understand the evolutionary dynamics and potential interplay of selective forces acting upon these regions. Finally, we identify selection signals within archaic introgressed segments to be mainly related to immune-associated genes. This finding indicates that archaic genetic contributions may have been pivotal in shaping the immune response of modern humans inhabiting islands in the Pacific. Further integration of past and recent demographic events experienced by populations of PNG into appropriate demography and selection models is required to enhance the understanding of adaptive events and their temporal dynamics. In addition, exploring analyses of polygenic selection could offer valuable insights into the genetics of adaptation of PNG populations. By characterizing signatures of positive selection in populations from PNG across different ecoregions, this work contributes to our understanding on the genetic basis of human adaptation in Pacific islanders.

The second paper looks at the very same issue as Gonzalez-Buenfil et at, but focusing on Tibetan women and how their own genetic adaptations to high altitude help them cope with pregnancies. I came across this second paper (“Higher oxygen content and transport characterize high-altitude ethnic Tibetan women with the highest lifetime reproductive success,” by Shenghao Ye et al, PNAS, 21.10.2024) via this post below, which has a pretty good explainer of its implications:

Human Evolution in Action: High-Altitude Adaptation on the Tibetan Plateau

In summary, what Ye et al add to the discussion is that the female ability to give birth in high altitude, not merely survive, is key to the adaptation of specific groups to living in such regions:

Women living at high altitudes (≥2,500 m) can encounter additional stress during pregnancy. High-altitude pregnancy increases the risk of preeclampsia or low birthweight (review in refs. 11 and 12), which raises the risk of maternal or infant death (13, 14). When comparing the pregnancy-related biology of Tibetan women with that of migrants to high altitudes, Tibetan women have lower hemoglobin concentration, higher oxygen saturation of hemoglobin and uterine artery blood flow, and heavier newborns (11, 15). Among Tibetan women who have completed childbearing, unelevated hemoglobin concentration, higher oxygen saturation, and a higher pulse rate correlate with higher lifetime reproductive success (16). This pattern of human variation suggests the action of natural selection on oxygen delivery phenotypes.

Abundant evidence of genetic selection is also available. Dozens of loci show genomic signals of selection among Tibetans (17–27). Few of those studies included biological traits, and the reported associations remain to be replicated to rule out chance findings or unknown confounding factors (28). However, among the selection signals, two are highly replicated across studies: the Egl-9 Family Hypoxia Inducible Factor 1 (EGLN1) and Endothelial PAS Domain Protein 1 (EPAS1) loci, both of which play pivotal early roles in the response to hypoxia and maintaining oxygen homeostasis. The EGLN1 locus encodes the oxygen sensor prolyl hydroxylase domain 2 (PHD2), which regulates the accumulation of hypoxia inducible factors (HIFs). EPAS1 encodes the alpha subunit of hypoxia inducible factor 2 (HIF2). HIF2 regulates the expression of hundreds of genes (29). These two loci harbor alleles unique to indigenous Tibetan Plateau populations and have been repeatedly associated with the characteristic unelevated hemoglobin concentrations (27).

Now for the questions from paying subscribers, on India, Hannibal Vs Egypt, resistance against slavery and Sertorius, Roman King of Spain: