Computational inference and analysis of ancestral genomes

DNA测序技术的进步导致了来自生命各个领域的大量物种的基因组测序。这为研究这些基因组的进化和解释进化事件的模式提供了一个令人难以置信的机会，以帮助识别基因组中的功能元件。这也为一种有趣的可能性打开了大门，即祖先物种的基因组可能通过计算从现存物种的基因组中推断出来。在这项提议中，我们首先致力于改进推断祖先DNA序列所需的计算工具。然后，我们建议利用这些推断的祖先序列来更好地了解人类基因组关键区域的起源以及重要作物和病原体物种的起源。特别是，我们将使用这些祖先序列来识别非常古老的进化事件，如转座子或伪基因的插入，这些事件塑造了早期哺乳动物的基因组，但其痕迹在现有的基因组中不再被识别。我们还将依靠我们推断祖先序列的能力来研究新的调节元件的起源，特别是那些可能具有灵长类特有特征的元件。最后，我们将训练计算预测者，以根据其推断的进化历史来识别基因组的功能元件，特别是调节元件。我们的项目将以软件和数据库的形式为基因组学社区带来重要的资源，这些软件和数据库将指导实验生物学家和基因学家进行分析。这也将有助于揭示我们基因组中关键元素的起源。

Advances in DNA sequencing technologies have resulted in the sequencing of the genomes of a large number of species from all domains of life. This represents an incredible opportunity to study the evolution of these genomes and interpret patterns of evolutionary events to help identifying functional elements in genomes. This also opens the door to the intriguing possibility that the genomes of ancestral species maybe be computationally inferred from those of extant species. In this proposal, we first aim to refine the computational tools needed to infer ancestral DNA sequences. We then propose to take advantage of these inferred ancestral sequences to better understand the origin of key regions of the human genome and of that of important crop and pathogen species. In particular, we will use these ancestral sequences to identify very ancient evolutionary events such as the insertion of transposons or pseudogenes, that have shaped the genomes of early mammals, but whose trace can no longer be recognized in extant genomes. We will also rely on our ability to infer ancestral sequences to study the genesis of new regulatory elements, in particular those that may have conferred primate-specific traits. Finally, we will train computational predictors to identify functional elements of the genome, in particular regulatory elements, on the basis of their inferred evolutionary history. Our project will bring important resources to the genomics community in the form of software and databases that will guide experimental biologists and genomicists in their analyses. It will also help shed light on the origin of key elements of our genome.