Responses to Selective Breeding for High Voluntary Activity in House Mice
对家鼠高自愿活动选择性育种的反应
基本信息
- 批准号:0543429
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-08-01 至 2010-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Living organisms are exceedingly complex. Simple, atomistic approaches to studying biological diversity have led to an inadequate understanding of the ways in which complex traits evolve. The general goal of the proposed research is to use a holistic approach to elucidate how a complex behavior (voluntary activity level) changes genetically in response to controlled and replicated cross-generational selective breeding. Two general hypotheses will be tested. First, increases in voluntary activity level will be associated with identifiable changes in brain structure and function that cause increased motivation for high activity. Second, increases in activity will be accompanied by changes in subordinate traits (e.g., muscle contractile properties) that support the behavior by enhancing organismal performance abilities (e.g., locomotor endurance or energetic efficiency). Thus, it is hypothesized that exceptional athletic performance requires both "brains" and "brawn." With previous NSF support, artificial selection for high voluntary wheel running was applied to an outbred population of laboratory mice. At generation 41, mice in the 4 replicate selected (S) lines ran almost three times as much as the 4 randombred control (C) lines (for females, 15.3 vs. 5.3 km/day; for males, 12.2 vs. 4.1). In the proposed research, selective breeding will continue and the S and C lines will be compared to elucidate the morphological, physiological, biochemical, and genetic bases of locomotor adaptations, as well as the neurobiological underpinnings high voluntary activity. General (consistent) responses to selection will be determined by statistical comparisons of all 4 S lines with all 4 C lines. Specific (unique) responses (multiple adaptive solutions) will be identified by comparing the 4 S lines. A key discovery of previous work is the "mighty mini-muscle" allele that has been favored by selection and gone to fixation in one of the S lines. This autosomal recessive causes a 50% reduction in hindlimb muscle mass, while doubling mass-specific aerobic capacity and altering contractile characteristics in ways that are hypothesized to enhance endurance running and the energetic efficiency of locomotion, but compromise sprinting abilities. This research will elucidate the physiological underpinnings of elevated maximal oxygen consumption, the power source for sustained locomotion, in the S lines and in mini-muscle vs. normal individuals. Mice will be exercise-tested on a treadmill and then submitted to biochemical and molecular analyses. The project includes tests of hypotheses that mini-muscles exhibit higher contractile efficiency and that this phenotype leads to reduced whole-animal costs of transport and reduced maximal sprint speeds. The investigators will map the putative mini-muscle locus to a chromosome, and identify possible candidate genes (in conjunction with in situ hybridizations and micro-array data). Finally, the researchers will test the hypotheses that S mice possess higher motivation to run on wheels, exhibit physiological withdrawal symptoms when wheel-deprived, and have altered dopamine physiology in key regions of the brain reward system. The proposed research will have general implications for how to study complex phenomena from an integrative and multidisciplinary perspective. It will identify biological determinants of a genetically defined, voluntary behavior that has major relevance for human health. The selectively bred lines of mice are a unique genetic resource and will be made available to other researchers for several additional projects. These studies will help to develop and promote the selected lines as an important model for studying effects of exercise on physical fitness, body-weight regulation, and aging. Research will emphasize training of undergraduates (including women and under-represented groups) and graduate students (four continuing Ph.D. students will participate), and will involve collaborations with eight other faculty and six other universities.
生物体是极其复杂的。研究生物多样性的简单、原子的方法导致对复杂性状进化方式的理解不足。本研究的总体目标是使用整体方法来阐明复杂行为(自愿活动水平)如何在受控和复制的跨代选择性育种中发生遗传变化。将测试两个一般假设。首先,自愿活动水平的增加将与大脑结构和功能的可识别变化有关,这些变化导致高活动的动机增加。其次,活动的增加将伴随着下属特征(如肌肉收缩特性)的变化,这些变化通过增强机体表现能力(如运动耐力或能量效率)来支持行为。因此,我们假设卓越的运动表现需要“大脑”和“肌肉”。在以前的国家科学基金会的支持下,人工选择高自愿轮跑被应用于一个近亲繁殖的实验室小鼠种群。在第41代,4个重复选择(S)系的小鼠几乎是4个随机对照(C)系的3倍(雌性,15.3 vs 5.3公里/天;雄性,12.2 vs 4.1公里/天)。在拟议的研究中,将继续进行选择性育种,并将S系和C系进行比较,以阐明运动适应的形态学,生理,生化和遗传基础,以及高自愿活动的神经生物学基础。对选择的一般(一致)反应将通过对所有4个S系和所有4个C系的统计比较来确定。将通过比较4条S线来确定特定(唯一)响应(多个自适应解决方案)。先前工作的一个关键发现是“强大的迷你肌肉”等位基因,它在选择中受到青睐,并在一个S系中固定下来。这种常染色体隐性遗传导致后肢肌肉质量减少50%,同时使质量特异性有氧能力加倍,并改变收缩特性,从而提高耐力跑和运动的能量效率,但损害短跑能力。这项研究将阐明最大耗氧量(持续运动的能量来源)升高的生理基础,在S线和小肌肉与正常人的对比中。小鼠将在跑步机上进行运动测试,然后进行生化和分子分析。该项目包括测试假设,迷你肌肉表现出更高的收缩效率,这种表型导致降低整个动物的运输成本和最大冲刺速度。研究人员将把假定的微型肌肉位点定位到染色体上,并确定可能的候选基因(结合原位杂交和微阵列数据)。最后,研究人员将测试以下假设:S小鼠有更高的动力在轮子上跑步,在没有轮子的情况下表现出生理上的戒断症状,并改变了大脑奖励系统关键区域的多巴胺生理学。所提出的研究将对如何从综合和多学科的角度研究复杂现象具有一般意义。它将确定与人类健康有重大关系的由基因决定的自愿行为的生物学决定因素。选择性繁殖的小鼠系是一种独特的遗传资源,将提供给其他研究人员用于其他几个项目。这些研究将有助于开发和推广所选品系,使其成为研究运动对身体健康、体重调节和衰老影响的重要模型。研究将强调对本科生(包括女性和代表性不足的群体)和研究生(四名继续攻读博士学位的学生将参加)的培训,并将涉及与其他八名教员和六所其他大学的合作。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Theodore Garland其他文献
Genetic variation and correlations between genotype and locomotor physiology in outbred laboratory house mice (Mus domesticus).
远交实验室家鼠(Mus Domesticus)基因型与运动生理学之间的遗传变异和相关性。
- DOI:
- 发表时间:
1999 - 期刊:
- 影响因子:0
- 作者:
Patrick A Carter;Theodore Garland;M. R. Dohm;Jack P. Hayes - 通讯作者:
Jack P. Hayes
Does Behavior Evolve First? Correlated Responses to Selection for Voluntary Wheel-Running Behavior in House Mice.
行为首先进化吗?
- DOI:
10.1086/730153 - 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Rahim H. Khan;Justin S. Rhodes;Isabelle A. Girard;Nicole E. Schwartz;Theodore Garland - 通讯作者:
Theodore Garland
Quantitative genetics of maximal oxygen consumption in a garter snake.
袜带蛇最大耗氧量的定量遗传学。
- DOI:
- 发表时间:
1990 - 期刊:
- 影响因子:0
- 作者:
Theodore Garland;Albert F. Bennett - 通讯作者:
Albert F. Bennett
Predictors of avian and mammalian translocation success: reanalysis with phylogenetically independent contrasts
鸟类和哺乳动物易位成功的预测因素:系统发育独立对比的重新分析
- DOI:
- 发表时间:
1998 - 期刊:
- 影响因子:0
- 作者:
C. M. Wolf;Theodore Garland;Brad Griffith - 通讯作者:
Brad Griffith
The evolution of demographic tactics in lizards: a test of some hypotheses concerning life history evolution
蜥蜴人口策略的演变:对有关生活史进化的一些假设的检验
- DOI:
10.1046/j.1420-9101.1998.11030329.x - 发表时间:
1998 - 期刊:
- 影响因子:2.1
- 作者:
Jean Clobert;Theodore Garland;Robert Barbault - 通讯作者:
Robert Barbault
Theodore Garland的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Theodore Garland', 18)}}的其他基金
Trade-offs, limits to adaptation, and multiple solutions: rules elucidated by selective breeding for high activity levels
权衡、适应限制和多种解决方案:通过选择性育种阐明高活性水平的规则
- 批准号:
2038528 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Continuing Grant
OPUS: Experimental Evolution of a Complex Trait in a Vertebrate Model Organism
OPUS:脊椎动物模型生物复杂性状的实验进化
- 批准号:
1655362 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Standard Grant
Responses to Selective Breeding for High Voluntary Activity in House Mice
对家鼠高自愿活动选择性育种的反应
- 批准号:
1121273 - 财政年份:2011
- 资助金额:
-- - 项目类别:
Standard Grant
DISSERTATION RESEARCH: Comparative Analysis of the Costs of Sexually Selected Traits within Swordtails and Platyfish
论文研究:剑尾鱼和鸭嘴鱼性选择性状成本的比较分析
- 批准号:
0709788 - 财政年份:2007
- 资助金额:
-- - 项目类别:
Standard Grant
Responses to Artificial Selection for Voluntary Activity in Mice
对小鼠自愿活动人工选择的反应
- 批准号:
0212567 - 财政年份:2002
- 资助金额:
-- - 项目类别:
Continuing Grant
Phylogenetic Analyses of the Evolution of Continuous Characters
连续性状进化的系统发育分析
- 批准号:
0196384 - 财政年份:2001
- 资助金额:
-- - 项目类别:
Standard Grant
Phylogenetic Analyses of the Evolution of Continuous Characters
连续性状进化的系统发育分析
- 批准号:
9981967 - 财政年份:2000
- 资助金额:
-- - 项目类别:
Standard Grant
REU: Responses to Artificial Selection for Voluntary Activity in House Mice
REU:对家鼠自愿活动人工选择的反应
- 批准号:
9728434 - 财政年份:1998
- 资助金额:
-- - 项目类别:
Continuing Grant
Morphological & Physiological Correlates of Locomotor Performance
形态学
- 批准号:
9723758 - 财政年份:1997
- 资助金额:
-- - 项目类别:
Standard Grant
Phylogenetic Analyses of the Evolution of Continuous Characters
连续性状进化的系统发育分析
- 批准号:
9509343 - 财政年份:1995
- 资助金额:
-- - 项目类别:
Standard Grant
相似海外基金
An investigation into novel methods of selective breeding for aquaculture fish based on their metabolic and growth rate
基于代谢和生长速度的水产养殖鱼类选育新方法的研究
- 批准号:
23K14013 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Early-Career Scientists
Meiotic recombination: how has this adaptive and evolutionary force been influenced by domestication and selective breeding?
减数分裂重组:这种适应性和进化力是如何受到驯化和选择性育种的影响的?
- 批准号:
NE/X011585/1 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Research Grant
Precision Beekeeping and Selective Breeding of the Honey Bee Using Multimodal Signal Processing and Machine Learning
利用多模态信号处理和机器学习进行精准养蜂和蜜蜂选择性育种
- 批准号:
548872-2019 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Alliance Grants
Low-Field MRI Development for Plant Disease Resistance Selective Breeding
低场 MRI 开发用于植物抗病选择性育种
- 批准号:
558182-2021 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Postdoctoral Fellowships
Precision Beekeeping and Selective Breeding of the Honey Bee Using Multimodal Signal Processing and Machine Learning
利用多模态信号处理和机器学习进行精准养蜂和蜜蜂选择性育种
- 批准号:
548872-2019 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Alliance Grants
Trade-offs, limits to adaptation, and multiple solutions: rules elucidated by selective breeding for high activity levels
权衡、适应限制和多种解决方案:通过选择性育种阐明高活性水平的规则
- 批准号:
2038528 - 财政年份:2021
- 资助金额:
-- - 项目类别:
Continuing Grant
Conference: Historical Memory: A Puget Sound Symposium on American Movements that Advocated Applying Selective Breeding Science to Humans
会议:历史记忆:倡导将选择性育种科学应用于人类的美国运动普吉特海湾研讨会
- 批准号:
1947049 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Standard Grant
Precision Beekeeping and Selective Breeding of the Honey Bee Using Multimodal Signal Processing and Machine Learning
利用多模态信号处理和机器学习进行精准养蜂和蜜蜂选择性育种
- 批准号:
548872-2019 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Alliance Grants
Effectivenss of a biocontrol agent which was improved by selective breeding for extended patch residence time
通过选择性育种延长斑块停留时间来提高生物防治剂的有效性
- 批准号:
19K06063 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of Transcriptome-Wide Predictive Models of Phenotypic Traits for Selective Breeding and Hybrid Performance Predictions in Maize
玉米选择性育种和杂交性能预测的表型性状全转录组预测模型的开发
- 批准号:
1711662 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Fellowship Award