Life at high altitude poses a dual challenge to mammals. First, energy demands are greater because environmental temperatures are generally lower than at low altitudes in the same latitudinal range. At the same time, however, low oxygen availability (hypoxia) limits an individual's capacity for energy expenditure. One of the physiological mechanisms animals use to cope with the low oxygen availability at high altitudes is to increase the amount of oxygen that can be carried from the lungs to the cells by increasing hemoglobin oxygen binding capacity (hemoglobin oxygen affinity). These changes can occur within the lifetime of an individual, but there are also known genetic differences between animals, within a species, for hemoglobin / oxygen binding ability. Alternatively, many animals are known to have the capacity to reversibly increase the size and functional capacity of various organ systems (including the cardiovascular system) in the face of increased demand (phenotypic plasticity) and some animals use this plasticity to cope with both low temperatures and hypoxia at high altitudes.
A model animal for the study of hemoglobin genetics is the deer mouse (Peromyscus maniculatus) which has been shown, in classic studies, to have genetic differences in hemoglobin type that are strongly correlated with native altitude, affect oxygen binding, and positively influence short-term exercise performance. Deer mice have also been shown to display increases in the size of the lungs, heart and digestive tract at high altitudes. One limitation of the work to date on both deer mice hemoglobins and organ phenotypic plasticity, is that it did not incorporate the influence of the site of gestational development and maturation (birth site), because it was performed on animals that were born and allowed to mature at low altitudes before they were moved to high altitude. It is known, however, that the gestational environment can be crucial to determining the anatomical and physiological capacity of adult animals. Thus the first goal of this research is to determine how energy expenditure (aerobic performance) is affected by gestational development at specific altitudes and if the hemoglobin genetics are still significant in determining the individual's physiological capacity to cope with life at high altitudes after accounting for plasticity of organ size. To test this, aerobic performance trials will be performed on mice with different hemoglobin genotypes born and reared at either high or low altitude.
Another unanswered question is the effect of hemoglobin genetics on long-term energy expenditure (i.e., over periods of days or weeks). This is an important issue new research has shown that sustainable energy demands of mice living at high altitudes can be nearly as high as previous measures of short term aerobic capacity. Young animals face an even greater challenge. Newly weaned juveniles are smaller than adults but have correspondingly higher mass-specific energy demands. Therefore it seems reasonable to expect that growth rates might be influenced by hemoglobin genotype and site of gestational development. Accordingly, the second goal of this research is to determine if hemoglobin genotype influences growth rates and sustainable metabolic rate under conditions of cold exposure and high-altitude hypoxia. To test this, mice with specific hemoglobin genotypes will be reared in semi-natural conditions at high and low test altitudes. We expect that mice with the appropriate hemoglobin genotype for a given test altitude will have the highest rates of sustainable metabolic output (measured as food consumption) and growth.
