Bérard Sèverine, Rivals Eric
L.I.R.M.M., UMR CNRS 5506, 161 rue Ada, F34392 Montpellier Cedex 5, France.
J Comput Biol. 2003;10(3-4):357-72. doi: 10.1089/10665270360688066.
In the class of repeated sequences that occur in DNA, minisatellites have been found polymorphic and became useful tools in genetic mapping and forensic studies. They consist of a heterogeneous tandem array of a short repeat unit. The slightly different units along the array are called variants. Minisatellites evolve mainly through tandem duplications and tandem deletions of variants. Jeffreys et al. (1997) devised a method to obtain the sequence of variants along the array in a digital code and called such sequences maps. Minisatellite maps give access to the detail of mutation processes at work on such loci. In this paper, we design an algorithm to compare two maps under an evolutionary model that includes deletion, insertion, mutation, tandem duplication, and tandem deletion of a variant. Our method computes an optimal alignment in reasonable time; and the alignment score, i.e., the weighted sum of its elementary operations, is a distance metric between maps. The main difficulty is that the optimal sequence of operations depends on the order in which they are applied to the map. Taking the maps of the minisatellite MSY1 of 609 men, we computed all pairwise distances and reconstructed an evolutionary tree of these individuals. MSY1 (DYF155S1) is a hypervariable locus on the Y chromosome. In our tree, the populations of some haplogroups are monophyletic, showing that one can decipher a microevolutionary signal using minisatellite maps comparison.
在DNA中出现的重复序列类别中,微卫星已被发现具有多态性,并成为基因图谱绘制和法医研究中的有用工具。它们由短重复单元的异质串联阵列组成。沿着阵列略有不同的单元称为变体。微卫星主要通过变体的串联重复和串联缺失而进化。杰弗里斯等人(1997年)设计了一种方法,以数字编码的形式获取沿着阵列的变体序列,并将此类序列称为图谱。微卫星图谱能够揭示在此类基因座上起作用的突变过程的细节。在本文中,我们设计了一种算法,用于在包含变体的缺失、插入、突变、串联重复和串联缺失的进化模型下比较两个图谱。我们的方法在合理的时间内计算出最优比对;并且比对得分,即其基本操作的加权和,是图谱之间的距离度量。主要困难在于最优操作序列取决于它们应用于图谱的顺序。以609名男性的微卫星MSY1图谱为例,我们计算了所有成对距离,并重建了这些个体的进化树。MSY1(DYF155S1)是Y染色体上的一个高变基因座。在我们构建的树中,一些单倍群的群体是单系的,这表明可以通过微卫星图谱比较来解读微观进化信号。