How the World’s Highest-Altitude Mammal Thrives

When researchers exploring the summit of the dormant Andean volcano Llullaillaco saw a small furry shape dart under a rock, they couldn't believe their eyes. No mammal had ever been found at Llullaillaco's 22,000 ft elevation, but here was an Andean leaf-eared mouse (Phyllotis vaccarum) scurrying across the volcano's frozen surface.

Now, in a new study published in Science, these researchers described P. vaccarum's biology in detail.¹ They identified unexpected adaptations in the Andean leaf-eared mouse's genome and metabolism that have helped it survive in a harsh environment where oxygen levels are reduced by half compared to sea level and the air temperature is below zero nearly all the time.

A Mammal for Every Altitude

One doesn't have to embark on a near-death hiking experience to see P. vaccarum. One of the factors that makes this mouse so unique is that it thrives at sea level as well as at extreme altitudes.

In the new study, Schuyler Liphardt, a bioinformatics data scientist at the University of Montana, and his colleagues collected 167 P. vaccarum specimens from across the species' habitable range. These included mice acquired during five high-elevation expeditions across the central Andes as well as from less vertiginous explorations at lower heights. They also looked at closely related mouse species that live at lower altitudes.

The team placed their mice in lab environments that mimicked the low-oxygen and low-temperature conditions that leaf-eared mice face at high altitudes. They found that highland P. vaccarum produced more body heat and had greater energy-producing activity in their muscles and brown body fat at these lower temperatures than both their lowland cousins and a closely related lower-altitude-living species, Darwin's leaf-eared mouse (P. darwini). This reflects that highland mice were able to maintain a high body temperature, even in conditions where oxygen restriction makes this process harder.

The team used whole-genome sequencing to investigate genetic differences between highland and lowland P. vaccarum populations and to identify unusual gene mutations that might help the mice survive at high altitude. The team identified that the genomes of highland and lowland P. vaccarum were generally very similar, with little genetic isolation from each other. This similarity made it easier to attribute the small changes that they could see to environmental adaptation.

The Metabolic Changes Sustaining P. vaccarum

The team identified several gene changes that may help the highland mice adapt to altitude. These included genes involved in lipid oxidation and synthesis, as well as other metabolic pathways. The team found that the mice didn't rely on changes to the oxygen-transporting molecule hemoglobin, a common adaptation in other high-altitude species. The team unexpectedly identified that highland mice had adaptations in their ability to metabolize plant toxins, which might be useful in a landscape where food is hard to come by. The authors proposed that some of the changes that helped mice adapt to low-oxygen conditions may have simultaneously helped it detoxify compounds in the plants it consumes.

Harsh environments like the slopes of Llullaillaco don't just throw single environmental challenges at life but present a range of pitfalls and challenges. The researchers concluded that P. vaccarum has fully adapted to a niche where food, oxygen, and warmth are all at a premium.