The Developmental-Genetic Basis for Integration and Canalization in the Vertebrate Skeleton

发展和进化以复杂的方式相互作用。发育是由自然选择决定的，但发育过程也会产生表型变异，这是进化的原材料。这是如何发生的很重要，因为发育过程的结构变化会影响进化的发生方式。具体地说，发育产生了特征之间的关系，这些特征往往会一起变化，从而共同进化。它还调节相对于潜在遗传变异表达的表型变异的量。这两种现象被称为一体化和运河化，它们是发展和进化之间复杂关系的症结所在。我们建议开发一种独特的遗传资源，合作交叉项目，来剖析整合和管道化的遗传学和发展。这种资源有一个至关重要的优势。这就是说，它由一大群基因多样化的小鼠品系组成，称为RIXS，这些品系在基因上是相同的，可以无限繁殖。此外，Rix小鼠是高度杂合子的，因此比其他实验室小鼠更像自然种群。因为这些小鼠可以无限繁殖，当我们发现导致感兴趣的变异的遗传变异时，我们可以产生更多这样的小鼠，用于进一步研究产生这种变异的机制。我们将这些小鼠的遗传学与转录学相结合，转录学是对基因表达模式的研究，以揭开整合和通道化背后的复杂遗传网络。

Development and evolution interact in complex ways. Development is shaped by natural selection, but developmental processes also generate the phenotypic variation which is the raw material for evolution. How this happens matters because developmental processes structure variation in ways that influence how evolution occurs. In particular, development produces relationships among traits that thus tend to vary together and thus co-evolve. It also modulates the amount of phenotypic variation that is expressed relative to underlying genetic variation. These two phenomena, called integration and canalization, are at the crux of the complex relationship between development and evolution. We propose to exploit a unique genetic resource, the Collaborative Cross Project, to dissect the genetics and development of integration and canalization. This resource has a crucial advantage. This is that it consists of a large and genetically diverse assemblage of mouse strains, called RIXs, that are genetically identical and can be reproduced indefinitely. In addition, the RIX mice are highly heterozygous and are thus much more like natural populations than other laboratory mice. Because these mice can be reproduced indefinitely, when we find genetic variants that cause variation of interest, we can generate more such mice for further study into the mechanisms that produce that variation. We combine the genetics of these mice with transcriptomics, which is the study of gene expression patterns, to unravel the complex genetic networks that underlie both integration and canalization.