"Evolutionary, developmental and functional aspects of skeletal variation in a mouse population selectively bred for increased long bone length"

表型变异通过选择为进化提供了燃料。尽管在进化过程中起着核心作用，表型变异的几个方面仍然知之甚少。其中包括：（i）表型变异与进化能力之间的关系，（ii）复杂性状中遗传、发育和表型变异之间的关系，以及（iii）表型变异与生物体功能和性能变异之间的关系。该提案概述了一个创新的研究计划，以综合的方式解决这些关系，在小鼠中使用人工选择。通过选择性繁殖胫骨长度的相对增加，该计划旨在修改胫骨长度和相关性状的（共）变异模式，并创建一个与对照群体相比具有相对较长寿命的小鼠群体。 三个研究目标将被解决：（1）量化表型和遗传相关性，以及进化性，在不同的选择压力下性状的变化，（2）揭示发育和遗传差异，与选择和对照小鼠之间观察到的胫骨长度差异相关，（3）评估胫骨长度增加对肌肉骨骼功能和性能指标的影响。为了实现这些目标，我们使用跨学科的方法，从进化定量遗传学，发育遗传学和脊椎动物功能形态学中借用理论，概念和实用工具，并利用尖端技术，如µCT成像和高通量转录组测序。 该计划的预期意义有三个方面。首先，它将提高我们对遗传和表型变异如何通过生物体发育联系起来的认识。其次，它将为骨骼生物学的综合研究创造一种新的小鼠资源。第三，也是最重要的一点，通过关注骨骼变异的机制基础，这项研究将大大推进我们对骨骼变异如何驱动脊椎动物进化变化和形态多样性的理解。

Phenotypic variation provides the fuel for evolution by means of selection. Despite this central role in the evolutionary process, several aspects of phenotypic variation remain poorly understood. These include: (i) the relationship between phenotypic variation and evolvability, (ii) the relationship between genetic, developmental and phenotypic variation in complex traits, and (iii) the relationship between phenotypic variation and variation in organismal function and performance. This proposal outlines an innovative research program that addresses these relationships in an integrative fashion, using artificial selection in mice. Through selective breeding for relative increases in tibia length, the program seeks to modify patterns of (co)variation in tibia length and correlated traits, and to create a population of mice with relatively longer tibiae compared to a control population. Three research objectives will be addressed: (1) to quantify how phenotypic and genetic correlations, and evolvability, change in traits under different selection pressures, (2) to uncover developmental and genetic differences that correlate with observed differences in tibia length between selected and control mice and (3) to assess the impact of increased tibia length on measures of musculoskeletal function and performance. To achieve these goals, we use an interdisciplinary approach, borrowing theory, concepts and practical tools from evolutionary quantitative genetics, developmental genetics and vertebrate functional morphology, and leveraging cutting-edge technologies such as µCT imaging and high-throughput transcriptome sequencing. The anticipated significance of this program is three-fold. First, it will improve our knowledge of how genetic and phenotypic variation are linked via organismal development. Second, it will create a novel mouse resource for integrative studies in skeletal biology. Third, and most importantly, by focusing on the mechanistic underpinnings of skeletal variation, this research will greatly advance our understanding of how skeletal variation drives evolutionary change and morphological diversity among vertebrates.