Estimation of duplication history under a stochastic model for tandem repeats
Estimation of duplication history under a stochastic model for tandem repeats
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DOI：
10.1186/s12859-019-2603-1
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发表时间：
2019-02-06
影响因子：
3
通讯作者：
Bruck, Jehoshua
中科院分区：
文献类型：
--
作者：
Farnoud, Farzad;Schwartz, Moshe;Bruck, Jehoshua
背景重复序列在许多生物的基因组中普遍存在，并被认为会引起基因沉默和快速形态变化等重要现象。由于串联重复序列中同一模式的多个副本的存在及其高度的变异性，它们包含了关于导致它们形成的突变的丰富信息。提取这些信息的能力可以增强我们对进化机制的理解。结果我们提出了一个通过串联复制和替换突变形成串联重复序列的随机模型。基于对该模型的分析，我们发展了一种方法来估计串联重复序列历史中重复和替换的相对突变率以及突变的总数。我们通过蒙特卡罗模拟对我们的估计方法进行了验证，结果表明它的性能优于最新的发现复制历史的算法。我们还将我们的方法应用于人类基因组中的串联重复序列，其中它展示了微卫星和小卫星的不同行为，并可用于比较染色体之间的突变率。据观察，在串联重复区域中表现出最高突变活性的染色体与那些被认为具有最高总体突变率的染色体是相同的。然而，与以往依赖于比较人类和黑猩猩基因组来测量突变率的工作不同，所提出的方法允许我们在单个基因组的基础上找到具有最高突变活性的染色体，本质上是通过比较串联重复模式的(近似)拷贝。结论串联重复在大多数生物中的普遍存在和所提出的方法的效率使得能够在广泛的环境中研究串联重复形成的各个方面及其周围序列。可在http://ips.lab.virginia.edu/smtr.上实现该估计方法
BackgroundTandem repeat sequences are common in the genomes of many organisms and are known to cause important phenomena such as gene silencing and rapid morphological changes. Due to the presence of multiple copies of the same pattern in tandem repeats and their high variability, they contain a wealth of information about the mutations that have led to their formation. The ability to extract this information can enhance our understanding of evolutionary mechanisms.ResultsWe present a stochastic model for the formation of tandem repeats via tandem duplication and substitution mutations. Based on the analysis of this model, we develop a method for estimating the relative mutation rates of duplications and substitutions, as well as the total number of mutations, in the history of a tandem repeat sequence. We validate our estimation method via Monte Carlo simulation and show that it outperforms the state-of-the-art algorithm for discovering the duplication history. We also apply our method to tandem repeat sequences in the human genome, where it demonstrates the different behaviors of micro- and mini-satellites and can be used to compare mutation rates across chromosomes. It is observed that chromosomes that exhibit the highest mutation activity in tandem repeat regions are the same as those thought to have the highest overall mutation rates. However, unlike previous works that rely on comparing human and chimpanzee genomes to measure mutation rates, the proposed method allows us to find chromosomes with the highest mutation activity based on a single genome, in essence by comparing (approximate) copies of the pattern in tandem repeats.ConclusionThe prevalence of tandem repeats in most organisms and the efficiency of the proposed method enable studying various aspects of the formation of tandem repeats and the surrounding sequences in a wide range of settings.AvailabilityThe implementation of the estimation method is available at http://ips.lab.virginia.edu/smtr.