Responses to Artificial Selection for Voluntary Activity in Mice

自然选择和性选择作用于复杂的、高度整合的表型，但关于如何在生物组织的多个层面上发生进化反应的理论是不全面的，现有的经验检验既不完整，也不确定。以前的NSF支持允许开发一种新的模型系统来研究对高运动活动选择的多水平进化反应。用外交系实验小鼠进行了高自愿性车轮跑的选育。到了第16代，4个重复选择(S)系的小鼠比4个随机选育的对照(C)系的小鼠多跑了170%(雌性，每天跑15vs.5.5公里)。这种差异延续到了第17代到第29代，表明了选择的限制。运动量的增加主要是通过提高跑步速度来实现的。S小鼠在断奶时跑得更多，至少持续18个月。拟议的研究将测试选择的生理极限的性质，阐明运动适应的机制，并探索活动增加的神经生物学。研究将强调对研究生和本科生以及博士后研究员的培养。最大有氧速度缺乏进化的可塑性被认为限制了车轮运行的进一步增加。增加和减少氧气对车轮运行和最大耗氧量的影响将被研究。运动的能量成本将在车轮和跑步机运行期间进行测量。肺弥散能力将通过形态计量学进行评估。将检查骨骼的组件在大小、形状、对称性和二次重塑数量方面的差异。肌球蛋白重链亚型在后肢肌肉中的表达将被量化，而出现在两个被选品系中的“强大的迷你肌肉”将被生化和电子显微镜表征。对于上述许多特征，将通过测量长期饲养的S和C小鼠来检验遗传和表型可塑性以及潜在的交互作用。以CFO作为神经元活性指标的免疫细胞化学方法，将用来比较S和C小鼠在安静和轮子高峰跑时的关键脑区(动机、奖励和成瘾；运动的自愿控制；空间记忆和学习)。结果将导致全面理解增加的活动水平是如何在模型哺乳动物系统中演变的。小鼠将被提供给其他研究人员，它们将成为研究运动对身体健康、健康和衰老影响的重要模型。

Natural and sexual selection act on complex, highly integrated phenotypes, but theories of how evolutionary response will occur across multiple levels of biological organization are non-comprehensive, and existing empirical tests are both fragmentary and inconclusive. Previous NSF support allowed development of a novel model system to study multi-level evolutionary responses to selection for high locomotor activity. Selective breeding for high voluntary wheel running was implemented with outbred laboratory mice. By generation 16, mice in the 4 replicate selection (S) lines ran 170% more than in the 4 randombred control (C) lines (for females, " 15 vs. 5.5 km/day). This difference continued for generations 17-29, indicating a selection limit. Increased activity has occurred primarily by higher running speed. S mice run more at weaning and for at least 18 months. Proposed research will test the nature of the physiological limit to selection, elucidate the mechanisms of locomotor adaptation, and explore the neurobiology of increased activity. Research will emphasize training of graduate and undergraduate students, as well as a postdoctoral researcher. A lack of evolutionary plasticity in maximal aerobic speed is hypothesized to limit further increase in wheel running. Effects of both increased and decreased oxygen on wheel running and on maximal oxygen consumption will be studied. The energetic cost of locomotion will be measured during both wheel and treadmill running. Lung diffusing capacity will be estimated morphometrically. Components of the skeleton will be examined for differences in size, shape, symmetry, and amount of secondary remodeling. Myosin heavy-chain isoform expression will be quantified in hindlimb muscle, and the "mighty mini-muscles" that occur in two of the selected lines will be characterized biochemically and by electron microscopy. For many of the above-mentioned traits, both genetic and phenotypic plasticity, and potential interactions, will be examined by measuring S and C mice that have been housed chronically with or without wheel access. Immunocytochemistry with cFos as an indicator of neuronal activity will be used to compare key brain regions in S and C mice at rest and during peak wheel running (motivation, reward, & addiction; voluntary control of movement; spatial memory & learning). Results will lead to a comprehensive understanding of how increased activity levels evolve in a model mammalian system. Mice will be made available to other researchers and they will be an important model for studying effects of exercise on physical fitness, health, and aging.