Genomic Basis of Vertebrate Diversity

描述：该项目的长期目标是了解脊椎动物表型多样性的基因组机制。基因组学的快速进展为几种生物体提供了几乎完整的序列。比较分析表明许多基本途径和基因网络在生物体之间是保守的。然而，不同物种的形态、生理和行为却存在明显而深刻的差异。产生这些关键差异的机制是什么？独特的性状是由少量还是大量基因变化控制的？什么样的变化？当生物体适应新环境时，是否存在重复使用的特定基因和机制？更好地理解这些机制能否有助于解释群体之间也存在的疾病易感性的巨大差异？斯坦福大学 CEGS 将在鱼类、小鼠和人类身上使用创新的方法组合，以确定脊椎动物自然种群中主要表型变化的分子基础。具体目标包括：1）对刺鱼进行杂交，开发出染色体、基因和突变的全基因组图谱，控制自然环境中各种新的形态、生理和行为特征； 2）测试哪些种群遗传测量提供了最可靠的围绕基因的“选择签名”，这些基因已知是世界各地许多不同自然种群中平行适应性变化的基础； 3) 组装刺鱼原Y染色体，并测试性别或常染色体重排是否在产生表型多样性方面发挥重要作用，或者是否在控制表型变化的基因组区域中富集； 4）测试是否重复使用特定基因和机制来控制许多不同脊椎动物的表型变化。初步数据表明，被确定为自然鱼类种群适应性变化基础的机制可能广泛预测包括人类在内的大量动物的适应性机制。假设在人类中受到选择的遗传区域将与在鱼类中受到选择的遗传区域进行比较。预计在人类自然变异和疾病易感性中发挥重要作用的区域将在小鼠中建模，生成新的模型系统，用于确认从人类群体遗传学和比较基因组学预测的功能变异。

DESCRIPTION: The long-term goal of this project is to understand the genomic mechanisms that generate phenotypic diversity in vertebrates. Rapid progress in genomics has provided nearly complete sequences for several organisms. Comparative analysis suggests many fundamental pathways and gene networks are conserved between organisms. And yet, the morphology, physiology, and behavior of different species are obviously and profoundly different. What are the mechanisms that generate these key differences? Are unique traits controlled by few or many genetic changes? What kinds of changes? Are there particular genes and mechanisms that are used repeatedly when organisms adapt to new environments? Can better understanding of these mechanisms help explain dramatic differences in disease susceptibility that also exist between groups? The Stanford CEGS will use an innovative combination of approaches in fish, mice, and humans to identify the molecular basis of major phenotypic change in natural populations of vertebrates. Specific aims include: 1) cross stickleback fish and develop a genome wide map of the chromosomes, genes, and mutations that control a broad range of new morphological, physiological, and behavioral traits in natural environments; 2) test which population genetic measures provide the most reliable "signatures of selection" surrounding genes that are known to have served as the basis of parallel adaptive change in many different natural populations around the world; 3) assemble the stickleback proto Y chromosome and test whether either sex or autosomal rearrangements play an important role in generating phenotypic diversity, or are enriched in genomic regions that control phenotypic change; 4) test whether particular genes and mechanisms are used repeatedly to control phenotypic change in many different vertebrates. Preliminary data suggests that mechanisms identified as the basis of adaptive change in natural fish populations may be broadly predictive of adaptive mechanisms across a surprisingly large range of animals, including humans. Genetic regions hypothesized to be under selection in humans will be compared to genetic regions under selection in fish. Regions predicted to play an important role in natural human variation and disease susceptibility will be modeled in mice, generating new model systems for confirming functional variants predicted from human population genetics and comparative genomics.