Of mice and men, making a living in rarefied air


High-elevation populations of deer mice have evolved “stickier” hemoglobin to cope with the thin atmosphere. (Animal Diversity Web)

ResearchBlogging.orgIt’s easy to walk through the woods and fields of North America and never spot Peromyscus maniculatus, the deer mouse, but you’ve probably heard them scampering off through the leaf litter or under cover of tall grass. They’re exceptionally widespread little rodents, found in forest undergrowth and fields from central Mexico all the way north to the Arctic treeline. In all this range, they look about the same: small and brown, with white underparts and big, sensitive ears.

That apparent sameness is deceptive, however.

A big, varied range presents lots of different environmental conditions to which a widespread species must adapt. And when that big, varied range includes the Rocky Mountains, one of those environmental conditions is as basic as the air itself. At high altitudes, atmospheric pressure is lower, which means lower partial pressure of oxygen, the gas that makes life as we know it work.

The fundamental problem at high altitude is to pull more oxygen from thinner air. Natural selection is good at solving problems, and it has multiple options for adapting a mammal to thinner air at high altitudes, to the extent that these traits are heritable. Selection could favor individuals who more readily respond to thin air by breathing faster and deeper, pulling in more air to make up for its lower oxygen content. Or selection could favor individuals who produce more red blood cells, so that a given volume of blood pumped through their lungs picks up more oxygen. Or, at the most basic level, selection could favor individuals whose individual red blood cells are better at picking up oxygen, via a new form of hemoglobin, the oxygen-binding molecule that packs every red blood cell.

This final option is the path selection took in deer mice. As the mammalogist Jay Storz has discovered, subspecies of Peromyscus maniculatus that live at higher altitudes have stickier hemoglobin, which soaks up more oxygen in thin air than the hemoglobin of deer mice from lower altitudes. This is a pattern repeated on a broader evolutionary scale across the mammals: llamas and vicuñas, close relatives that both evolved in the rarefied air of the Andes, have “stickier” hemoglobin than most other mammals [PDF].

The pattern is also repeated in another, even more widespread mammal: humans.


Mount Everest, the pinnacle of the Himalayas. (Flickr: phobus)

The evolution of Homo sapiens in response to high-altitude low-oxygen conditions is one of the most thoroughly described examples of human evolution, thanks to years of work by Cynthia Beall and her colleagues. Previous research going back to the nineteenth century established that people native to the Andes produce more red blood cells and more hemoglobin [PDF] than people from lower altitudes—a naturally selected form of the “blood doping” practiced by élite athletic cheats that helps draw more oxygen from every breath.

Meanwhile, populations that have lived for generations on the Tibetan Plateau don’t have high-capacity blood like native Andeans. Yet high-altitude Tibetans maintain higher concentrations of oxygen in their blood than lowland natives can manage at the same altitude, though. Instead of evolving new blood capacity, Tibetans make their circulatory system work harder, with a high-powered ventilatory response. This response is the sensitivity to low oxygen conditions that prompts you to breathe more rapidly—people native to low altitudes also increase their breathing rate in response to moving to high altitude conditions, but they don’t keep it up for more than a few days. In high-altitude Tibetans, this physiological acclimation has become a permanent feature.

In other words, natural selection has come up with two separate solutions to the problem of low oxygen at high altitude, within the same species.

Beall and her collaborators traced the presence of this “high oxygen saturation” trait in Tibetan families to establish that it has a genetic basis, and even identified part of the specific fitness benefit associated with carrying the high oxygen saturation gene in the thin air of the Tibetan plateau. In villages located at 4,000 meters or higher, women with the high oxygen saturation trait are about as likely to become pregnant, and carry those pregnancies to term, as women without the trait—but their children were more likely to survive over the longer term.


Children of Tibetan women carrying the “high oxygen saturation” allele have a higher survival rate. (Flickr: The AlleyTree)

This adaptation to the heights is one of the most well documented examples of natural selection in human populations, with more detail known even than in the case of adult lactose tolerance. It’s a demonstration of natural selection’s resourcefulness, acting on random mutations to come up with entirely different solutions in distantly related populations on opposite sides of the world—adapting living things of all kinds to life at the very ends of the Earth. ◼

This post has its origin in the 2011 National Academies Northstar Summer Institute for science education, where I learned about the full extent of Cynthia Beall’s work.


Beall, C. (2004). Higher offspring survival among Tibetan women with high oxygen saturation genotypes residing at 4,000 m. Proc. Nat. Acad. Sciences USA, 101 (39), 14300-14304 DOI: 10.1073/pnas.0405949101

Beall, C. (2006). Andean, Tibetan, and Ethiopian patterns of adaptation to high-altitude hypoxia. Integrative and Comparative Biology, 46 (1), 18-24 DOI: 10.1093/icb/icj004

Beall, C. (2007). Two routes to functional adaptation: Tibetan and Andean high-altitude natives. Proc. Nat. Acad. Sciences USA, 104 (S1), 8655-60 DOI: 10.1073/pnas.0701985104

Storz, J. (2007). Hemoglobin function and physiological adaptation to hypoxia in high-altitude mammals. Journal of Mammalogy, 88 (1), 24-31 DOI: 10.1644/06-MAMM-S-199R1.1

Storz, J., Runck, A., Sabatino, S., Kelly, J., Ferrand, N., Moriyama, H., Weber, R., & Fago, A. (2009). Evolutionary and functional insights into the mechanism underlying high-altitude adaptation of deer mouse hemoglobin. Proc. Nat. Acad. Sciences USA, 106 (34), 14450-5 DOI: 10.1073/pnas.0905224106