Patterns of background nucleotide substitution in the human lineage
人类谱系中背景核苷酸取代的模式
基本信息
- 批准号:7077029
- 负责人:
- 金额:$ 20.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-04-01 至 2011-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): Knowledge of the patterns and rates of background substitution is essential for the identification and analysis of functional sequences in the human genome. Provided this knowledge it should be possible to identify functional sequences in comparison of two or more genomes. Such sequences will stand out as those that have changed either significantly less or significantly more than expected under the estimated rates of background substitution. Despite this central importance, patterns of background substitution are poorly known. Questions of whether rates of background substitution vary across the human genome and whether these rates have been evolving in the human lineage remain controversial. Major difficulties lie in identifying sequences that evolve under no functional constraint and also in devising methods of inferences given the existence of a rapid neighbor-dependent CpG to TpG/CpA transition prevalent in mammalian DNA. The high rate and the neighbor-dependence of this process substantially complicate all inferences of substitution, even those of single-nucleotide substitutions at non-CpG sites. This project will utilize a new maximum likelihood method capable of simultaneous inference of the rates of CpG to TpG/CpA transition and of the rates of single-nucleotide substitution significantly beyond the point of naive saturation. This method will be applied to the abundant sequences of dead copies of transposable elements in the human and other mammalian genomes deposited over the last 200-300 million years. This analysis will provide essential new information regarding the evolution of patterns of substitution in mammalian genomes, will create fine-scale (1-5 Mbp) genomic maps of substitution patterns and rates of the human and other mammalian genomes, and will investigate genomic determinants of background substitution patterns in mammals.
描述(由申请人提供):背景置换模式和速率的知识对于鉴定和分析人类基因组中的功能序列至关重要。提供了这方面的知识,应该有可能确定功能序列的比较两个或更多的基因组。这样的序列将脱颖而出,因为那些已经改变了显着更少或显着超过预期的估计率的背景替代。尽管有这种核心重要性,背景替代的模式知之甚少。背景替换率是否在人类基因组中存在差异,以及这些比率是否在人类谱系中不断进化,这些问题仍然存在争议。主要的困难在于识别序列的发展下没有功能的限制,并在设计的推理方法,由于存在一个快速的邻居依赖性CpG TPG/CpA过渡普遍存在于哺乳动物DNA。这一过程的高速率和邻居依赖性大大复杂化了所有取代的推断,即使是那些在非CpG位点的单核苷酸取代。该项目将利用一种新的最大似然法,能够同时推断CpG向TpG/CpA转变的速率和显著超过幼稚饱和点的单核苷酸取代的速率。这种方法将被应用于人类和其他哺乳动物基因组中大量的转座因子死亡拷贝的序列,这些序列在过去的2亿至3亿年中被保存下来。这项分析将提供有关哺乳动物基因组中替代模式演变的重要新信息,将创建人类和其他哺乳动物基因组的替代模式和速率的精细比例(1-5 Mbp)基因组图谱,并将调查哺乳动物背景替代模式的基因组决定因素。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Dmitri Petrov其他文献
Dmitri Petrov的其他文献
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