Harding R M, Boyce A J, Clegg J B
MRC Molecular Haematology Unit, University of Oxford, John Radcliffe Hospital, Headington, Oxford, England.
Genetics. 1992 Nov;132(3):847-59. doi: 10.1093/genetics/132.3.847.
Variable numbers of tandem repeats (VNTRs), which include hypervariable regions, minisatellites and microsatellites, can be assigned together with satellite DNAs to define a class of noncoding tandemly repetitive DNA (TR-DNA). The evolution of TR-DNA is assumed to be driven by an unbiased recombinational process. A simulation model of unequal exchange is presented and used to investigate the evolutionary persistence of single TR-DNA lineages. Three different recombination rules are specified to govern the expansion and contraction of a TR-DNA lineage from an initial array of two repeats to, finally, a single repeat allele, which cannot participate in a misalignment and exchange process. In the absence of amplification or selection acting to bias array evolution toward expansion, the probability of attaining a target array size is a function only of the initial number of repeats. We show that the proportions of lineages attaining a targeted array size are the same irrespective of recombination rule and rate, demonstrating that our simulation model is well behaved. The time taken to attain a target array size, the persistence of the target array, and the total persistence time of repetitive array structure, are functions of the initial number of repeats, the rate of recombination, and the rules of misalignment preceding recombinational exchange. These relationships are investigated using our simulation model. While misalignment constraint is probably greatest for satellite DNA it also seems important in accounting for the evolution of VNTR loci including minisatellites. This conclusion is consistent with the observed nonrandom distributions of VNTRs and other TR-DNAs in the human genome.
可变数目串联重复序列（VNTRs），包括高变区、小卫星和微卫星，可以与卫星DNA一起归类，以定义一类非编码串联重复DNA（TR-DNA）。TR-DNA的进化被认为是由一个无偏向的重组过程驱动的。本文提出了一个不等交换的模拟模型，并用于研究单个TR-DNA谱系的进化持久性。指定了三种不同的重组规则来控制TR-DNA谱系从最初的两个重复序列阵列扩展和收缩，最终形成单个重复等位基因，该等位基因不能参与错配和交换过程。在没有扩增或选择使阵列进化偏向于扩展的情况下，达到目标阵列大小的概率仅取决于初始重复序列的数量。我们表明，无论重组规则和速率如何，达到目标阵列大小的谱系比例都是相同的，这表明我们的模拟模型表现良好。达到目标阵列大小所需的时间、目标阵列的持久性以及重复阵列结构的总持续时间，都是初始重复序列数量、重组速率以及重组交换前错配规则的函数。使用我们的模拟模型研究了这些关系。虽然错配约束可能对卫星DNA最为严格，但它似乎在解释包括小卫星在内的VNTR位点的进化方面也很重要。这一结论与人类基因组中VNTRs和其他TR-DNAs的非随机分布观察结果一致。
