Living at high altitude pushes the physiology of the mammals that choose to live there to its limits, yet many species rise to the challenge. Some populations of deer mice can be found at 4300 m, where the extreme habitat requires them to cope with low levels of oxygen in the thin air, but keeping warm is an equal challenge for the small mammals. To overcome the cold, deer mice shiver to produce heat, which uses more of the scarce oxygen; and in highland natives, evolution has carefully tuned the cascade of steps that funnel oxygen to their muscles. Yet, their lowland relatives are not completely barred from these heights; given time, they can adjust their physiology to life in thin air, although highland natives are just better at coping with high altitudes. Whether generations of high-altitude evolution have shaped the highlander's oxygen transport cascade in unique ways, or whether they use the same old tricks as altitude-nurtured lowlanders, only better, is still unclear. Untangling the contribution of each – nature versus nurture – is not easy, but shivering mice are shedding some light on this old question.

Kevin Tate at McMaster University in Canada and his collaborators in the USA, set out to investigate exactly how low- and highland-native deer mice supply their bodies with oxygen when at high altitude. In the lab they kept groups of mice at different combinations of temperature (warm and cold) and oxygen (normal and low) allowing for an adjustment period in each condition, and then exposed the mice to frigid air (–5°C) with about half the normal oxygen content, simulating the harsh conditions at the peak. While the mice shivered to stay warm, the team measured their oxygen consumption to see whether highland natives (nature) had an edge over lowlanders that experienced an adjustment period at altitude (nurture).

When the mice were allowed to adjust to cold and low-oxygen conditions, both lowlanders and highlanders coped equally well in the simulated high altitude, using the same amount of oxygen. However, when the mice had adjusted to the warm low-oxygen conditions, the lowlanders struggled at altitude and were unable to match the high oxygen consumption of highlanders, whose high-altitude nature gave them an advantage not provided by the adjustment period alone. To answer why the deer mouse highlanders coped better, the team took a closer look at the different steps in the cascade that carries oxygen to their tissues.

The heartbeat of the lowlanders that had adjusted to the warm, low-oxygen condition slowed at altitude, which could hamper oxygen transport by the blood. However, the highlanders were unaffected by the heart-slowing effects of low oxygen and increased most steps in the oxygen transport cascade: their lungs extracted more oxygen from the air, their hearts beat stronger, their blood contained more oxygen and their muscles extracted more of it from the blood. While some of these steps in the oxygen transport cascade were naturally higher in the highlanders, others increased only after adjusting to the low-oxygen condition and in combination they boosted the highlander's performance.

Both low- and highland natives can benefit from a period of adjustment before ascending a peak. However, highlanders have evolved favourable traits along their oxygen transport cascade that provide an advantage at altitude and, more importantly, that can magnify the benefits of the adjustment period. As for the old question of nature versus nurture, it seems that highland-native deer mice cope with high altitude using a little of both, and perhaps a sprinkle of just toughing it out. However, a high-altitude lifestyle that relies on shivering for survival just doesn't sound that much fun and maybe when choosing their habitat the lowland mice had it right all along.

Tate
,
K. B.
,
Wearing
,
O. H.
,
Ivy
,
C. M.
,
Cheviron
,
Z. A.
,
Storz
,
J. F.
,
McClelland
,
G. B.
and
Scott
,
G. R.
(
2020
).
Coordinated changes across the O2 transport pathway underlie adaptive increases in thermogenic capacity in high-altitude deer mice
.
Proc. R. Soc. B
287
,
20192750
.