Evolutionary dynamics of microsatellite DNA
Evolutionary dynamics of microsatellite DNA
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DOI：
10.1007/s004120000089
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发表时间：
2000-09-01
期刊：
影响因子：
1.6
通讯作者：
Schlötterer, C
中科院分区：
文献类型：
--
作者：
Schlötterer, C
在过去的十年中，微卫星已经发展成为最受欢迎的遗传标记之一。尽管微卫星分析被广泛使用，但微卫星DNA突变动态的整体图像才刚刚开始出现。在这里，我回顾了普遍同意和有争议的结果关于微卫星DNA的突变动力学。微卫星是短的DNA序列延伸，其中一个主题的1至6个碱基串联重复。一段时间以来，人们已经知道这些序列在个体之间的重复数可能不同。随着聚合酶链反应（PCR）技术的出现，微卫星DNA的这种特性被转化为高度通用的遗传标记（Litt and Luty 1989; Tautz 1989; Weber and May 1989）。不同长度的聚合酶链反应产物可以用微卫星可变区侧翼的引物扩增。由于高通量毛细管测序仪或质谱仪的可用性，等位基因的大小不再是微卫星分析中的瓶颈，微卫星的几乎随机分布及其高水平的多态性极大地促进了遗传图谱的构建（Dietrich et al. 1994; Dib et al. 1996），并使随后的几个基因的定位克隆成为可能。几乎在同一时间，微卫星被确定为个人身份识别和亲子鉴定的首选标记。基于PCR的微卫星分析的高灵敏度不仅对法医学非常有益，而且开辟了全新的研究领域，例如分析DNA量有限的样品（例如，许多群居昆虫）或降解的DNA（例如，粪便，博物馆材料）（Schlotterer和Pemberton 1998）。最近，微卫星分析也被用于群体遗传学（Goldstein和Schlotterer 1999）。与等位酶相比，微卫星的优点是，原则上，有几千个潜在的多态性标记。然而，微卫星应用于群体遗传学问题需要更详细地了解微卫星DNA的突变过程，因为群体遗传学所涵盖的进化时间框架通常太长，以至于不能忽略新的微卫星突变。对微卫星DNA进化的额外兴趣来自于发现三核苷酸重复，一类特殊的微卫星，与人类神经退行性疾病有关（例如，脆性X和亨廷顿病）。因此，详细了解微卫星不稳定性的过程是对更好地了解这些人类神经退行性疾病的重要贡献。
Within the past decade microsatellites have developed into one of the most popular genetic markers. Despite the widespread use of microsatellite analysis, an integral picture of the mutational dynamics of microsatellite DNA is just beginning to emerge. Here, I review both generally agreed and controversial results about the mutational dynamics of microsatellite DNA.Microsatellites are short DNA sequence stretches in which a motif of one to six bases is tandemly repeated. It has been known for some time that these sequences can differ in repeat number among individuals. With the advent of polymerase chain reaction (PCR) technology this property of microsatellite DNA was converted into a highly versatile genetic marker (Litt and Luty 1989; Tautz 1989; Weber and May 1989). Polymerase chain reaction products of different length can be amplified with primers flanking the variable microsatellite region. Due to the availability of high-throughput capillary sequencers or mass spectrography the sizing of alleles is no longer a bottleneck in microsatellite analysis.The almost random distribution of microsatellites and their high level of polymorphism greatly facilitated the construction of genetic maps (Dietrich et al. 1994; Dib et al. 1996) and enabled subsequent positional cloning of several genes. Almost at the same time, microsatellites were established as the marker of choice for the identification of individuals and paternity testing. The high sensitivity of PCR-based microsatellite analysis was not only of great benefit for forensics, but opened completely new research areas, such as the analysis of samples with limited DNA amounts (e.g., many social insects) or degraded DNA (e.g., feces, museum material) (Schlotterer and Pemberton 1998).More recently, microsatellite analysis has also been employed in population genetics (Goldstein and Schlotterer 1999). Compared with allozymes, microsatellites offer the advantage that, in principle, several thousand potentially polymorphic markers are available. Nevertheless, the application of microsatellites to population genetic questions requires a more detailed understanding of the mutation processes of microsatellite DNA as the evolutionary time frames covered in population genetics are often too long to allow novel microsatellite mutations to be ignored. Additional interest in the evolution of microsatellite DNA comes from the discovery that trinucleotide repeats, a special class of microsatellites, are involved in human neurodegenerative diseases (e.g., fragile X and Huntington's disease). A detailed understanding of the processes underlying microsatellite instability is therefore an important contribution toward a better understanding of these human neurodegenerative diseases.