I’ve written about Thierry Legault’s phenomenal imagery of space before; with relatively modest equipment, but excellent foresight, he gets astronomical shots of surpassing beauty.

He sent me a note earlier that he had something new and cool, and he wasn’t kidding: a video of the ISS in 3D!

Coooooooool.

To see it in 3D you don’t need glasses; it’s a bit like those Magic Eye posters. Look at the video, and cross your eyes slightly to merge the left and right images into one. Then hit play (move your mouse into the frame to get the video controls). It may take you a while to get the hang of it, but it’s worth the effort! I found it easiest to do when my eyes were about 50 cm (18 inches) from my monitor; for reference, on my screen the image of the ISS is about 8 cm (3 inches) high.

What you’re seeing here is actually only one video of the ISS. As it orbits the Earth, the ISS actually keeps the same attitude — that is, the same physical orientation. It only seems to rotate because Thierry centered it in the video. Take an orange or something like it in your hand, and move it straight across your field of vision. If you start on the right, you’ll be able to see more of the left side of the orange; as you move it to the left you’ll start to see more of the right side of the orange. It’s as if it’s rotating, but really you’re just changing the angle between you and the two sides of the orange. If you keep your head pointed right at the orange as it passes, you can see this more clearly. Note that it gets bigger as it gets closer, just as the ISS does in the video.

What Thierry did then was pretty tricky: he offset the left video in time a bit from the one on the right. We see 3D with our eyes because the angle from our left eye to an object is slightly different than the angle using our right eye (this effect is called parallax). Our brain processes these slightly different angles to construct an object with depth — it’s how all 3D works, from red-green anaglyphs to movies in the theater. And since the ISS was apparently rotating with time in the video, all Thierry had to do was offset the two videos a bit to trick the brain into thinking it’s seeing two different angles from your eyes; the brain does the rest.

Note that the ISS was over 300 km away when he took these shots on April 24th from France. It was also moving at over a degree per second across the sky, which is pretty fast. To make the animation cleaner, he took every 15 frames and combined them, a standard practice to make fuzzy images somewhat sharper. He also sped the animation up 2.5 times.

This video is extremely well done, and a fantastic exercise in clever thinking. Thierry continues to amaze me every time he does something new… but he’ll have a hard time topping this!

Video used with permission.

You probably are aware that different populations have different tolerances for high altitudes. Himalayan sherpas aren’t useful just because they have skills derived from their culture, they’re actually rather well adapted to high altitudes because of their biology. Additionally, different groups seem to have adapted to higher altitudes independently, exhibiting convergent evolution. But in terms of physiological function they aren’t all created equal, at least in relation to the solutions which they’ve come to to make functioning at high altitudes bearable. In particular, it seems that the adaptations of the peoples of Tibet are superior than those of the peoples of the Andes. Superior in that the Andean solution is more brute force than the Tibetan one, producing greater side effects, such as lower birth weight in infants (and so higher mortality and lower fitness).

The Andean region today is dominated by indigenous people, and Spanish is not the lingua franca of the highlands as it is everyone in in the former colonial domains of Spain in the New World. This is largely a function of biology; as in the lowlands of South America the Andean peoples were decimated by disease upon first contact (plague was spreading across the Inca Empire when Pizzaro arrived with his soldiers). But unlike the lowland societies the Andeans had nature on their side: people of mixed or European ancestry are less well adapted to high altitudes and women without tolerance of the environment still have higher miscarriage rates.

So despite the suboptimal nature of the Andean adaptations vis-a-vis the Tibetan ones, they are certainly better than nothing, and in a relative sense have been very conducive to higher reproductive fitness. And yet why might the Andeans have kludgier adaptations than Tibetans? One variable to consider is time. The probability is that the New World was populated by humans only for the past ~10,000-15,000 years or so, with an outside chance of ~20,000 years (if you trust a particular interpretation of the genetic data, which you probably shouldn’t). By contrast, modern humans have had a presence in the center of Eurasia for ~30,000 years. Generally when populations are exposed to new selective regime the initial adaptations are drastic and exhibit major functional downsides, but they’re much better than the status quo (remember, fitness is relative). Over time genetic modifications mask the deleterious byproducts of the genetic change which emerged initially to deal with the new environment. In other words, selection perfects design over time in a classic Fisherian sense as the genetic architecture converges upon the fitness optimum.*

Another parameter may be the variation available within the population, as the power of selection is proportional to the amount of genetic variation, all things equal. The peoples of the New World tend to be genetically somewhat homogeneous, probably due to the fact that they went through a bottleneck across Berengia, and that they’re already sampled from the terminus of the Old World. A physical anthropologist once told me that the tribes of the Amazon still resemble Siberians in their build. It may be that it takes a homogeneous population with little extant variation a long time indeed to shift trait value toward a local ecological optimum (tropical Amerindians are leaner and less stocky than closely related northern populations, just not particularly in relation to other tropical populations). In contrast, populations in the center of Eurasia have access to a great deal of genetic variation because they’re in proximity to many distinctive groups (the Uyghurs for example are a recent hybrid population with European, South Asian and East Asian ancestry).

So that’s the theoretical backdrop for the differences in adaptations. Shifting to the how the adaptations play out concretely, some aspects of the physiology of Tibetan tolerance of high altitudes are mysterious, but one curious trait is that they actually have lower levels of hemoglobin than one would expect. Andean groups have elevated hemoglobin levels, which is the expected “brute force” response. Interestingly it seems that evolution given less time or stabilizing at a physiologically less optimal equilibrium is more comprehensible to humans! Nature is often more creative than us. In contrast the Tibetan adaptations are more subtle, though interestingly their elevated nitric acid levels may facilitate better blood flow. Though the inheritance patterns of the trait had been observed, the genetic mechanism underpinning it has not been elucidated. Now a new paper in Science identifies some candidate genes for the various physiological quirks of Tibetans by comparing them with their neighbors, and looking at the phenotype in different genotypes with the Tibetan population. Genetic Evidence for High-Altitude Adaptation in Tibet:

Tibetans have lived at very high altitudes for thousands of years, and they have a distinctive suite of physiological traits that enable them to tolerate environmental hypoxia. These phenotypes are clearly the result of adaptation to this environment, but their genetic basis remains unknown. We report genome-wide scans that reveal positive selection in several regions that contain genes whose products are likely involved in high-altitude adaptation. Positively selected haplotypes of EGLN1 and PPARA were significantly associated with the decreased hemoglobin phenotype that is unique to this highland population. Identification of these genes provides support for previously hypothesized mechanisms of high-altitude adaptation and illuminates the complexity of hypoxia response pathways in humans.

Here’s what they did. First, Tibetans are adapted to higher altitudes, Chinese and Japanese are not. The three groups are relatively close genetically in terms of ancestry, so the key is to look for signatures of positive selection in regions of the genome which have been identified as possible candidates in terms of functional significance in relation to pathways which may modulate the traits of interest. After finding potential regions of the genome possibly under selection in Tibetans but not the lowland groups, they fixed upon variants which are at moderate frequencies in Tibetans and noted how the genes track changes in the trait.

This figure from the supplements shows how the populations are related genetically:

In a worldwide context the three groups are pretty close, but they also don’t overlap. The main issue I would have with this presentation is that the Chinese data is from the HapMap, and they’re from Beijing. This has then a northeast Chinese genetic skew (I know that people who live in Beijing may come from elsewhere, but recent work which examines Chinese phylogeography indicates that the Beijing sample is not geographically diversified), while ethnic Tibetans overlap a great deal with Han populations in the west of China proper. In other words, I wouldn’t be surprised if the separation between Han and Tibetan was far less if you took the Chinese samples from Sichuan or Gansu, where Han and Tibetans have lived near each other for thousands of years.

But these issues of phylogenetic difference apart, we know for a fact that lowland groups do not have the adaptations which are distinctive to the Tibetans. To look for genetic differences they focused on 247 loci, some from the HIF pathway, which is important for oxygen homeostasis, as well genes from Gene Ontology categories which might be relevant to altitude adaptations. Table 1 has the breakdown by category.

Across these regions of the genome they performed two haplotype based tests which detect natural selection, EHH and iHS. Both of these tests basically find regions of the genome which have reduced variation because of a selective sweep, whereby selection at a specific region of the genome has the effect of dragging along large neutral segments adjacent to the original copy of the favored variant. EHH is geared toward detection of sweeps which have nearly reached fixation, in other words the derived variant has nearly replaced the ancestral after a bout of natural selection. iHS is better at picking up sweeps which have not resulted in the fixation of the derived variant. The paper A Map of Recent Positive Selection in the Human Genome outlines the differences between EHH and iHS in more detail. They looked at the three populations and wanted to find regions of the genome where Tibetans, but not the other two groups, were subject to natural selection as defined by positive signatures with EHH and iHS. They scanned over 200 kb windows of the genome, and found that 10 of their candidate genes were in regions where Tibetans came up positive for EHH and iHS, but the other groups did not. Since these tests do produce false positives they ran the same procedure on 240 random candidate genes (7 genes were in regions where Chinese and Japanese came up positive, so these were removed from the set of candidates), and came up with average EHH and iHS positive hits of ~2.7 and ~1.4 genes after one million resamplings (specifically, these are genes where Tibetans were positive, the other groups negative). Their candidate genes focused on altitude related physiological pathways yielded 6 for EHH and 5 for iHS (one gene came up positive for both tests, so 10 total). This indicates to them these are not false positives, something made more plausible by the fact that we know that Tibetans are biologically adapted to higher altitudes and we have an expectation that these genes are more likely than random expectation to have a relationship to altitude adaptations.

Finally, they decided to look at two genes with allelic variants which exist at moderate frequencies in Tibetans, EGLN1 and PPARA. The procedure is simple, you have three genotypes, and you see if there are differences across the 31 individuals by genotype in terms of phenotype. In this case you want to look at hemoglobin concentration, where those who are well adapted have lower concentrations. Figure 3 is rather striking:

Even with the small sample sizes the genotypic effect jumps out at you. This isn’t too surprising, previous work has shown that these traits are highly heritable, and that they vary within the Tibetan population. There’s apparently a sex difference in terms of hemoglobin levels, so they did a regression analysis, and it illustrates how strong the genetic effect from these alleles are:

My main question: why do Tibetans still have variation on these genes after all this time? Shouldn’t they be well adapted to high altitudes by now? A prosaic answer may be that the Tibetans have mixed with other populations recently, and so have added heterozygosity through admixture. But there are several loci here which are fixed in Tibetans, and not the HapMap Chinese and Japanese. For admixture to be a good explanation one presumes that the groups with which the Tibetans mixed would have been fixed for those genes as well, but not the ones at moderate frequencies. This may be true, but it seems more likely that admixture alone can not explain this pattern. As the Andean example suggests adaptation to high altitudes is not easy or simple. Until better options arrive on the scene, kludges will suffice. It may be that the Tibetans are still going through the sieve of selection, and will continue to do so for the near future. Or, there may be balancing dynamics on the genes which exhibit heterozygosity, so that fixation is prevented.

No matter what the truth turns out to be, this is surely just the beginning. A deeper investigation of the genetic architecture of Andeans and Ethiopians, both of which have their own independent adaptations, will no doubt tell us more. Finally, I wonder if these high altitude adaptations have fitness costs which we’re not cognizant of, but which Tibetans living in India may have some sense of.

Citation: Tatum S. Simonson, Yingzhong Yang, Chad D. Huff, Haixia Yun, Ga Qin, David J. Witherspoon, Zhenzhong Bai, Felipe R. Lorenzo, Jinchuan Xing, Lynn B. Jorde, Josef T. Prchal, & RiLi Ge (2010). Genetic Evidence for High-Altitude Adaptation in Tibet Science : 10.1126/science.1189406

* Additionally, it may be that archaic hominin groups were resident in the Himalaya for nearly one million years. Neandertal admixture evidence in Eurasians should change our priors when evaluating the possibility for adaptive introgression on locally beneficial alleles.

Image Credit: Wikimedia Commons