Genetics and Plasticity in Adaptation to Altitude in the Deer Mouse

鹿鼠适应海拔的遗传和可塑性

• 批准号: 0111604
• 负责人: Kimberly Hammond
• 金额: $ 29万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0111604&HistoricalAwards=false
• 关键词: Genetics; Plasticity; Adaptation; Altitude; Deer

0111604 Hammond & ChappellLife 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.

[11:16 . 04]高海拔地区的生活给哺乳动物带来了双重挑战。首先，能源需求更大，因为在同一纬度范围内，环境温度通常低于低海拔地区。然而，与此同时，低氧可用性（缺氧）限制了个体的能量消耗能力。动物应对高海拔低氧的生理机制之一是通过增加血红蛋白氧结合能力（血红蛋白氧亲和力）来增加从肺部输送到细胞的氧气量。这些变化可能在个体的一生中发生，但在同一物种内，动物之间的血红蛋白/氧结合能力也存在已知的遗传差异。另外，许多动物在面对增加的需求（表型可塑性）时，已知具有可逆地增加各种器官系统（包括心血管系统）的大小和功能容量的能力（表型可塑性），一些动物利用这种可塑性来应对高海拔地区的低温和缺氧。研究血红蛋白遗传学的模型动物是鹿鼠（Peromyscus maniculatus），经典研究表明，鹿鼠血红蛋白类型的遗传差异与当地海拔高度密切相关，影响氧结合，并对短期运动表现产生积极影响。在高海拔地区，鹿鼠的肺、心脏和消化道也会增大。迄今为止，关于鹿鼠血红蛋白和器官表型可塑性的研究有一个局限性，那就是它没有考虑到妊娠发育和成熟地点（出生地点）的影响，因为研究对象是在低海拔地区出生并在低海拔地区成熟的动物，然后才被转移到高海拔地区。然而，众所周知的是，妊娠环境对决定成年动物的解剖和生理能力至关重要。因此，本研究的第一个目标是确定能量消耗（有氧表现）如何受到特定海拔地区妊娠发育的影响，以及考虑到器官大小的可塑性后，血红蛋白遗传学是否仍然在决定个体在高海拔地区应对生活的生理能力方面具有重要意义。为了验证这一点，将对在高海拔和低海拔地区出生和饲养的具有不同血红蛋白基因型的小鼠进行有氧运动性能试验。另一个悬而未决的问题是血红蛋白基因对长期能量消耗（即数天或数周）的影响。这是一个重要的问题，新的研究表明，生活在高海拔地区的小鼠的可持续能量需求几乎和以前测量的短期有氧能力一样高。年幼的动物面临着更大的挑战。刚断奶的幼鱼体型比成年鱼小，但相应地有更高的质量比能量需求。因此，预期生长速率可能受到血红蛋白基因型和妊娠发育部位的影响似乎是合理的。因此，本研究的第二个目标是确定在寒冷暴露和高海拔缺氧条件下，血红蛋白基因型是否影响生长速度和可持续代谢率。为了验证这一点，将在高海拔和低海拔的半自然条件下饲养具有特定血红蛋白基因型的小鼠。我们预计，在给定的测试高度，具有适当血红蛋白基因型的小鼠将具有最高的可持续代谢输出率（以食物消耗来衡量）和生长。