Microevolution of the mammalian limb skeleton: from genes and development to morphology and performance

哺乳动物肢体骨骼的微进化：从基因和发育到形态和性能

• 批准号: RGPIN-2018-03912
• 负责人: Rolian, Campbell
• 金额: $ 2.04万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=663614
• 关键词: Microevolution; mammalian; limb; skeleton; genes

Background: Mammals show a remarkable diversity of limb proportions, which evolved as adaptations for specific types of locomotion (e.g., sprinting, hopping). The long-term vision of my research program is to uncover the developmental, functional and evolutionary mechanisms that make this skeletal diversity possible. To do so, I developed the Longshanks mouse, which has 15-20% longer shin bones (tibiae), but the same body mass as random-bred control mice.*** Research Objectives: Over the next five years, I will address three complementary objectives: (1) to define the contributions of specific developmental genetic pathways to the longer limbs and altered limb proportions of Longshanks; (2) to probe the relationship between Longshanks' modified limb morphology and its locomotor performance; and (3) to determine the impact of tibia selection on coevolution of other skeletal and soft tissue traits. *** Scientific Approach: For Objective 1, we will use histology and gene expression tools to: (1) test the hypothesis that the signaling factor Dlk1 regulates the number of proliferating cells in the growth plates during long bone development, and thus plays a major role in increasing bone length in Longshanks, and (2) determine whether different gene pathways are involved in increasing Longshanks' overall skeletal size, vs. the size of each limb bone. For Objective 2, we will use high-speed video and force platforms to test the hypothesis that Longshanks' increased limb bone length improves its running and sprinting performance, e.g., by increasing its maximum sprint speeds and/or endurance. For Objective 3, we will combine micro-CT imaging, and quantitative genetics tools, to determine if and how other parts of Longshanks' body (e.g., cranium, internal organs) have changed in response to tibia selection, and whether this has impacted Longshanks' overall capacity to evolve.*** Significance: My research program integrates data that spans genes to morphology to whole organism performance, to address long-standing questions on the mechanistic basis of evolutionary change. Anticipated outcomes will have broad impacts across evolutionary biology and related fields (e.g., evolutionary developmental biology, ecology, paleontology), through the following breakthroughs: (1) uncovering key cell and molecular drivers of morphological diversity, (2) understanding how species, both living and extinct, adapt to their environments through improved organismal performance, and (3) identifying evolutionary constraints that have shaped morphological diversity in living and fossil species. The proposed studies will also improve public understanding of evolution, by providing clear and relatable examples of evolution in action, and will contribute to the training of Canada's next generation of life scientists, with transferable skills in bioinformatics, movement science and digital imaging. **

背景：哺乳动物的肢体比例表现出显著的多样性，这些肢体比例是为了适应特定类型的运动(如短跑、跳跃)而进化的。我的研究计划的长期愿景是揭示使这种骨骼多样性成为可能的发育、功能和进化机制。为此，我培育了Longshanks小鼠，它的胫骨(胫骨)比随机饲养的对照组小鼠长15%-20%，但体质量相同。*研究目标：在接下来的五年里，我将致力于实现三个相辅相成的目标：(1)确定特定发育遗传路径对长腿更长肢体和改变肢体比例的贡献；(2)探讨Longshanks改良肢体形态与其运动能力之间的关系；以及(3)确定胫骨选择对其他骨骼和软组织性状协同进化的影响。*科学方法：对于目标1，我们将使用组织学和基因表达工具：(1)检验信号因子Dlk1在长骨发育过程中调节生长板中的增殖细胞数量，从而在增加长腿骨长度方面发挥主要作用的假设，以及(2)确定是否有不同的基因途径参与增加长腿骨的整体骨骼大小与每个肢体骨骼的大小。对于目标2，我们将使用高速视频和FORCE平台来测试这样的假设，即Longshanks增加的肢体骨骼长度改善了它的跑步和短跑成绩，例如，通过增加它的最大冲刺速度和/或耐力。对于目标3，我们将结合Micro-CT成像和定量遗传学工具，来确定Longshanks身体的其他部分(例如，头骨、内脏)是否以及如何随着胫骨的选择而发生变化，以及这是否影响了Longshanks的整体进化能力。*意义：我的研究计划整合了从基因到形态再到整个生物体表现的数据，以解决长期存在的进化变化的机制基础上的问题。预期结果将通过以下突破对进化生物学和相关领域(如进化发育生物学、生态学、古生物学)产生广泛影响：(1)揭示形态多样性的关键细胞和分子驱动因素；(2)了解物种，无论是生存的还是灭绝的，如何通过改善生物性能来适应其环境；以及(3)确定形成活物种和化石物种形态多样性的进化制约因素。拟议的研究还将提高公众对进化论的理解，提供清晰和相关的进化论实例，并将有助于培训加拿大下一代生命科学家，他们拥有生物信息学、运动科学和数字成像方面的可转让技能。**