Computational comparative genomics: inferring and analyzing ancestral genomes architectures

计算比较基因组学：推断和分析祖先基因组架构

• 批准号: 249834-2011
• 负责人: Chauve, Cedric
• 金额: $ 2.62万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=570742
• 关键词: Computational; comparative; genomics; inferring; analyzing

The central problem that I will address is the inference of ancestral genome architectures. Due to DNA decay, most ancestral genomes cannot be obtained directly by sequencing (from fossils for example). Instead, they must be inferred through the comparison of the genomes of their extant descendants, an approach which was pioneered by cytogeneticists. More recently, following the sequencing and assembly of a growing number of eukaryotic genomes, this approach was investigated by computational biologists. This resulted in a lively methodological debate between both communities, which has now been more or less settled, at least in the case of mammalian genomes. The next bottleneck, for vertebrate genomes, is now to infer the genome structure of the amniote ancestor, and of older ancestors, which is the starting point of my research program. The main motivation for inferring ancient eukaryote ancestors is to push further our current understanding of the evolutionary forces that shape today's genomes. The proposed research program has two main goals: 1. To develop methodologies and efficient algorithms for inferring ancestral genome architectures, composed of Contiguous Ancestral Regions (CARs) and Ancestral Link age Groups (ALGs), both at a high resolution (on the order of a few hundreds kbs). The originality of my approach will be to rigorously combine principles and concepts from different problems: physical mapping, comparative genome assembly, genome rearrangements methods, synteny conservation models, phylogenomics. 2. To infer ancestral genomes in important groups such as vertebrate genomes and angiosperms, and to combine these ancestral genomes with extant genomes to address important questions related to the evolution of eukaryotic genomes. I will investigate problems such as the inference reliable genome rearrangement events, mapping of breakpoint regions and regulatory regions on ancestral chromosomes to evaluate the link between gene regulation and synteny breakage, and measuring the correlation between GC content and chromosomes size.

我将解决的中心问题是祖先基因组结构的推断。由于DNA 由于基因组的衰变，大多数祖先的基因组不能直接通过测序获得（例如从化石中）。相反地， 它们必须通过比较它们现存后代的基因组来推断，这种方法 是由细胞遗传学家开创的。最近，随着越来越多的基因的测序和组装， 在真核生物基因组的研究中，计算生物学家研究了这种方法。这导致了一场热闹的 两个社区之间的方法论辩论，现在或多或少已经解决，至少在这种情况下， 哺乳动物基因组。脊椎动物基因组的下一个瓶颈，现在是推断古脊椎动物祖先和更古老祖先的基因组结构，这是我研究计划的起点。推断古代真核生物祖先的主要动机是进一步推动我们目前对塑造今天基因组的进化力量的理解。拟议的研究计划有两个主要目标： 1.开发用于推断祖先基因组结构的方法和有效算法，包括连续祖先区域（汽车）和祖先联系年龄组（ALG），两者都具有高分辨率（几百kbs的量级）。 我的方法的独创性将是严格结合联合收割机的原则和概念，从不同的问题：物理作图，比较基因组组装，基因组重排方法，同线性保护模型，基因组学。 2.推断脊椎动物基因组和被子植物等重要类群的祖先基因组，并将这些祖先基因组与现存基因组联合收割机，以解决与真核生物基因组进化相关的重要问题。我将调查的问题，如推断可靠的基因组重排事件，定位断裂点区域和调控区域的祖先染色体上，以评估基因调控和同线性断裂之间的联系，并测量GC含量和染色体大小之间的相关性。