Adaptation and acclimatization to altitude in newborn rodents.

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Mammals (human included), living at high altitude (>2,500 m) face serious consequences due to the reduced availability of oxygen (O2). The oldest animal and human populations have evolved at least for thousands of years in this environment, and now are considered as being genetically adapted to altitude. More recently, over the past 500 to 50 years, lowland migrants have established new settlements in North and South America and in Tibet, and have introduced (intentionally or not) new mammalian species to altitude. It is fascinating to observe that for most of these human and animal populations adaptation to altitude is an ongoing process. Some of these populations show poor adaptation to altitude compared to the more ancient populations. Our research is designed to understand the differences between a successful and a failed adaptation to altitude. To this aim, we are comparing the effects of low O2 level in rats and mice. These species are interesting because they have both been introduced in South America in the past centuries, and they have shown divergent success: only mice have colonized the high and low altitude regions, while rats remain exclusively a lowland species. *What causes this difference? Our recent work performed with our colleagues of the Bolivian Institute for Altitude Biology (IBBA, La Paz, 3600m above sea level), and in our laboratory in Québec, showed that successful adaptation to altitude is tightly dependent on O2 availability during postnatal development. We have found that when newborn rats are exposed to low O2 their lungs suffer permanent damages, which reduces the rate at which O2 flows from the lungs to the blood. Under similar conditions the lungs of newborn mice are much less damaged. In addition, when exposed to low O2 levels, mammals are able to "hyperventilate" (increase the volume of air they are breathing). This response is mediated by specialized parts of the brain (the respiratory control system) and helps bring more oxygen to the lungs. Our experiments have shown that newborn mice exposed to low O2 are able to hyperventilate, but this response is much less important in newborn rats. Interestingly, divergent responses to low O2 levels in human infants and newborn have also been evoked to explain why different humans population have different adaptation at altitude.*To explain these differences, we need to understand how low O2 level can induce biological responses. At the cellular level, mammals possess molecules that can sense O2 level, and induce specific responses when it decreases. These systems are present in the lung and in the respiratory control system, but so far their precise role in driving adaptation to altitude is not completely understood. Our leading hypothesis is that these mechanisms are responding differently to low O2 in rats and mice. We will use several molecular biology tools to understand more precisely these differences and their consequences. *These studies are relevant for a broad array of life sciences including physiology and genetics, but also ecology and evolution, because they aim at identifying the mechanisms explaining altitude distribution in 2 rodent species. They also provide a rich and stimulating challenge for students, who will have to perform demanding technical approaches and understand how their data fits into this fascinating field of research.