Kimberly A. Hammond - US grants

Wild animals are often well-equipped to handle variable, harsh environments. Interestingly, most wild animals also will acquire parasites during their lives. Some parasites kill their host, but others cause a chronic, sub-lethal infection. The PIs goal is to determine if chronic, sub-lethal parasite infection affects host physiology and consequently host reproduction. The PIs will examine 1) host intestinal physiology and energy allocation (glucose absorption, fat and lean masses), 2) host reproduction (litter production, offspring masses), and 3) growth and survival of host offspring (linear growth measures, body mass).

The broader significance of this project spans several research areas. First, this project has implications for the field of life-history evolution because it will determine if an infected host's reproduction is constrained by its ability to acquire or process energy. Second, because this research uses wild, rather than laboratory, mice it will aid in the understanding of how wild animals cope with chronic infections that may alter multiple aspects of reproduction. Third, this research will provide much needed empirical data for mathematical models of how sub-lethal parasites affect host reproduction. Finally, because chronic parasite infection of humans is common in third world countries, this research may help understand the effects of sub-lethal parasites on human reproduction.

DBI-9987605
Hammond, Kimberly A.

This project is to support a colony of deer mice (Peromyscus maniculatus) that are derived from a high altitude population in the White Mountains of California. This species is unique because it carries a hemoglobin polymorphism that may confer an advantage for living at high altitudes under reduced oxygen and cold conditions. Thus, the species is an ideal model for the initiation of a large-scale study of adaptation to high altitude or other hypoxic conditions in warm-blooded animals. This colony is also Hanta virus (Sin Nombre strain) free so it is a valuable resource for Hanta virus research and represents no health or safety risks. Finally, the colony is outbred and has been maintained to preserve maximum heterozygosity.

The colony will represent an excellent, Hanta virus free stock that will be of use to other researchers for the study of Hanta virus and its associated physiology in small mammals. In addition, the colony will be an excellent resource for the study of the ecology an evolutionary biology of altitudinal acclimation and adaptation in small mammals. The funds will support building of a breeding colony that will be deposited in the Peromyscus Stock Center at the University of South Carolina when they can be maintained and made widely available to other researchers.

0111604 Hammond & Chappell

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.

Deer mice inhabit the broadest altitudinal distribution of any North American mammal, from below sea level (Death Valley) to above 4000 m where hypoxic conditions are the norm and the deer mice must adapt their physiology to satisfy oxygen demand. It appears from recent research that previously described hemoglobin/genetic adaptations exert very modest effects on oxygen acquisition and are insufficient alone to explain the success and activity levels of deer mice at high altitude. Deer mice also display changes in organ sizes (e.g., heart, lung) that vary along the altitude gradient and are correlated with improved aerobic performance necessary for high levels of activity. This project will investigate the extent to which changes in lung size and function contribute to the observed increases in activity in adult mice acclimated to high altitude. Students will participate in all data collection aspects of the proposed research and contribute to the development of educational modules for undergraduate classes and outreach efforts to the public and citizen science workshops in the Southern California region. Results from the study will be further disseminated through publication in peer-reviewed journals and presentations at scientific meetings.

Preliminary data from the principle investigator's lab suggests that the capacity of the lung to deliver oxygen at high altitude is the first critical limit in the oxygen cascade and that, in deer mice, the lung has the capacity to remodel to meet that demand. Such pulmonary plasticity would be highly adaptive if species are moving upward in elevation as the climate becomes warmer. This project will therefore test the hypothesis that some animals have the capacity to remodel lung architecture and optimize function throughout their lives. Changes in the cardio-pulmonary tissues between the high- and low-altitude acclimated mice will be assessed through histologic and physiologic assays. Modified gas composition will be used in direct respirometry tests of lung performance in control (normoxic) and altitude-acclimated animals. Lung volume, alveolar surface area, capillary density and blood gas composition will be tested to determine the extent to which organ size, architecture, and composition changes contribute to high altitude acclimation. Results from this study will inform our understanding of how small mammal populations that are forced to move to higher altitudes and harsh or variable conditions as a result of climate change will cope with their relocation.