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，但关于进化反应如何在生物组织的多个层次上发生的理论是不全面的，现有的经验测试既不完整又不确定。 先前的NSF支持允许开发一种新的模型系统，以研究对高运动活性选择的多层次进化反应。 用远交系实验小鼠进行高自主跑轮的选育。 到第16代，4个重复选择（S）系中的小鼠比4个随机繁殖的对照（C）系中的小鼠多跑170%（对于雌性，15与5.5 km/天）。 这种差异持续到第17-29代，表明选择限制。 活动的增加主要是由于跑步速度的提高。 S小鼠在断奶时跑得更多，至少18个月。 拟议的研究将测试自然选择的生理限制，阐明运动适应的机制，并探索增加活动的神经生物学。 研究将强调研究生和本科生的培训，以及博士后研究员。 假设最大有氧速度缺乏进化可塑性，限制了轮跑的进一步增加。 将研究增加和减少氧气对车轮运行和最大耗氧量的影响。 运动的能量消耗将在轮和跑步机跑步期间测量。 将通过形态测定法估计肺弥散量。 将检查骨骼组件的大小、形状、对称性和继发性重塑量的差异。 将在后肢肌肉中定量肌球蛋白重链亚型表达，并将通过生物化学和电子显微镜表征在两个选定系中出现的“强大的迷你肌肉”。 对于许多上述性状，遗传和表型可塑性，以及潜在的相互作用，将通过测量长期饲养的S和C小鼠（有或没有轮访问）进行检查。 将使用cFos作为神经元活动指标的免疫细胞化学比较S和C小鼠在休息和峰值轮跑步期间的关键脑区（动机、奖励、成瘾;运动的自主控制;空间记忆学习）。 结果将导致一个全面的了解如何增加活动水平在模型哺乳动物系统的演变。 小鼠将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.