Jin L, Macaubas C, Hallmayer J, Kimura A, Mignot E
Department of Genetics, Stanford University, CA 94305, USA.
Proc Natl Acad Sci U S A. 1996 Dec 24;93(26):15285-8. doi: 10.1073/pnas.93.26.15285.
The understanding of the mutational mechanism that generates high levels of variation at microsatellite loci lags far behind the application of these genetic markers. A phylogenetic approach was developed to study the pattern and rate of mutations at a dinucleotide microsatellite locus tightly linked to HLA-DQB1 (DQCAR). A random Japanese population (n = 129) and a collection of multiethnic samples (n = 941) were typed at the DQB1 and DQCAR loci. The phylogeny of DQB1 alleles was then reconstructed and DQCAR alleles were superimposed onto the phylogeny. This approach allowed us to group DQCAR alleles that share a common ancestor. The results indicated that the DQCAR mutation rate varies drastically among alleles within this single microsatellite locus. Some DQCAR alleles never mutated during a long period of evolutionary time. Sequencing of representative DQCAR alleles showed that these alleles lost their ability to mutate because of nucleotide substitutions that shorten the length of uninterrupted CA repeat arrays; in contrast, all mutating alleles had relatively longer perfect CA repeat sequences.
对在微卫星位点产生高度变异的突变机制的理解，远远落后于这些遗传标记的应用。我们开发了一种系统发育方法，来研究与HLA - DQB1紧密连锁的二核苷酸微卫星位点（DQCAR）的突变模式和速率。对一个随机的日本人群（n = 129）和一组多民族样本（n = 941）进行了DQB1和DQCAR位点分型。然后重建了DQB1等位基因的系统发育，并将DQCAR等位基因叠加到该系统发育树上。这种方法使我们能够对具有共同祖先的DQCAR等位基因进行分组。结果表明，在这个单一微卫星位点内，DQCAR突变率在等位基因之间差异极大。一些DQCAR等位基因在很长的进化时间内从未发生突变。对代表性DQCAR等位基因的测序表明，这些等位基因由于核苷酸替换缩短了不间断CA重复序列的长度而失去了突变能力；相反，所有发生突变的等位基因都有相对较长的完美CA重复序列。
