Systematic Identification of Genome Structural Variation in Mimulus

基因组测序项目通常产生一个单一的参考基因组。虽然非常有用，但这掩盖了该物种基因组序列或结构中潜在的重要变异。直到最近，由于缺乏合适的方法学，甚至还不可能在事后系统地调查亚微观基因组的结构变异。研究人员将应用一种新的方法在全基因组范围内识别结构变异，其中一个或多个基因的染色体位置因个体而异。这将通过将特定的遗传杂交与大规模平行的DNA杂交技术相结合来实现。这项研究将使用进化模式植物Mimulus的密切相关物种进行。这项工作的具体目标是确定位置可变的染色体区域的频率、位置、大小和基因含量。Mimulus基因组资源的可用性，它适合在自然种群中进行实地研究，以及该属的巨大多样性，使其成为研究自然发生的基因组结构变异的生态和进化后果的极佳模式。最近的发现表明，同一物种内不同个体之间的基因含量通常不同。例如，已经发现成对的人类在大约12个染色体区域的拷贝数量上彼此不同，每个区域有近50万个碱基对。这些区域包含神经、发育和新陈代谢的重要基因。尽管这样的研究表明结构变异可能是常见的，尽管结构变异对适应和物种形成有潜在的贡献，但目前对自然种群中基因拷贝数和基因位置变异的丰富性几乎一无所知。因此，这项工作为理解一类迄今在很大程度上被忽视的分子变异的功能、生态和进化后果奠定了基础。

Genome sequencing projects typically produce a single reference genome. While tremendously useful, this glosses over potentially important variation in the sequence or structure of the genome within that species. Until recently, it has not even been possible to systematically survey sub-microscopic genome structural variations after the fact, due to the lack of suitable methodology. The investigators will apply a novel method for the genome-wide identification of structural variants in which the chromosomal location of one or more genes differs among individuals. This will be achieved by combining a particular genetic cross with massively-parallel DNA hybridization technology. The study will be done using closely related species of the model evolutionary plant, Mimulus. The specific goal of this work is to identify the frequency, position, size and gene content of chromosomal regions that are variable in position. The availability of genomic resources in Mimulus, its amenability to field studies in natural populations, and the tremendous diversity of the genus, make it an excellent model in which to study the ecological and evolutionary consequences of naturally-occurring genome structural variation. Recent findings suggest that gene content routinely differs among individuals within a species. For example, pairs of humans have been found to differ from each other in the copy number of approximately a dozen chromosomal regions of nearly half a million base pairs each. These regions contain genes of neurological, developmental, and metabolic importance. Though studies such as this suggest that structural variation may be common, and despite the potential contribution of structural variation to adaptation and speciation, almost nothing is currently known about the abundance of gene copy number and gene location variation in natural populations. Thus, this work sets the stage for understanding the functional, ecological and evolutionary consequences of a class of molecular variation that has been hitherto largely neglected.