Genome assembly. chromosomal organization and comparative genomics of multiple bird species: beyond "catalogues of genes"

想象一下，试图在一个城镇中导航，只有A-Z的索引来指导你，而不是街道地图。从本质上讲，这就是当一个新物种的基因组被测序时发生的事情。老式的技术通常是先“勾勒出街道的轮廓”，然后再用基因序列来填补空白。这项新技术(所谓的“下一代测序”)更便宜、更快，但在区分基因之间的关系方面做得很差。从本质上讲，下一代测序组件只不过是基因的目录，几乎没有整体基因组的明显结构。幸运的是，这个问题可以用一种名为“FISH”的技术来纠正，这种技术可以从下一代测序项目中获取数据，并在基因出现在基因组中的正确位置时直接显示基因。在这个项目中，我们打算用25-30个最近完成的鸟类基因组序列来做这件事。鸟类是种类最多的动物之一，大约有1万个活着的物种。许多是人类疾病和发展的模型，对农业(包括肉类和鸡蛋)至关重要。其他鸟类受到威胁或濒临灭绝，随着全球变暖的迫在眉睫，研究鸟类生态和保护鸟类的分子工具至关重要。比较一个基因组和另一个基因组的整体结构也是可能的，有点像比较布局相似的城镇的地图。我们已经开发了在线工具，可以一次直接显示几种鸟类基因组之间的相似和差异。当然，这些鸟类基因组之间的差异是通过进化过程中发生的变化而产生的。这个项目的主要目标之一是找出这种情况是如何发生的以及为什么会发生。我们有许多想法，比如我们认为在基因组中或多或少可能发生进化重排的地方可能有不同的“基因签名”。我们认为，整个过程可能与我们的基因在生殖细胞中重组的机制有关。我们还认为，“漂浮”在鸟类基因组周围的小片段DNA可能起到了一定的作用。最后，我们得到了世界各地众多实验室的压倒性支持，他们都对鸟类基因组学感兴趣，希望利用我们的在线资源提出自己的生物学问题。出于这个原因，我们认为这个项目不仅将帮助我们了解鸟类的进化，还将使英国成为这类工作的中心国际中心。

Imagine trying to navigate through a town with only the index from your A-Z to guide you and not the street map. In essence, this is what happens when the genome of a new species is sequenced. Old fashioned technology used to "sketch the outline of the streets" first before filling in the gaps with the gene sequence. The new technology (so called "Next Generation Sequencing") is much cheaper and quicker but is quite poor at sorting out where the genes are in relation to one another. Essentially, Next Generation Sequencing assemblies are little more than catalogues of genes with little structure of the overall genome apparent. Fortunately this problem can be rectified using a technique called "FISH" that can take the data from next generation sequencing projects and visualise directly the genes as they appear in their rightful place in the genome. In this project we intend to do this with 25-30 recently completed genome sequences from birds. Birds are among the most diverse animals with around 10,000 living species. Many are models for human disease and development and are critical to agriculture (both meat and eggs). Others are threatened or endangered and, with impending global warming, molecular tools for the study of ecology and conservation of birds are essential. It is also possible to compare the overall structure of one genome with another, somewhat like comparing the maps of towns with similar layouts. We have developed online tools that can directly visualize the similarities and differences between the genomes of several birds at a time. Of course the differences between these bird genomes came about through changes that happened during evolution. One of the main aims of this project is to find out how and why this occurred. We have a number of ideas such as we think there may be different "gene signatures" at the places in the genome where evolutionary rearrangements are more or less likely to occur. We think that the whole process may be related to the mechanisms by which our genes recombine in our germ cells. We also think there may be a role for small pieces of DNA that "float around" these bird genomes. Finally, we have received overwhelming support from numerous laboratories all over the world, all of whom are interested in bird genomics and who would wish to use our online resource to ask biological questions of their own. For this reason we feel that this project not only will help us understand evolution in birds but also establish the UK as a central international hub for work of this kind.