DNA microsatellites: Agents of evolution?
DNA microsatellites: Agents of evolution?
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DOI：
10.1038/scientificamerican0199-94
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发表时间：
1999-01-01
影响因子：
3
通讯作者：
Wills, C
中科院分区：
文献类型：
--
作者：
Moxon, ER;Wills, C
人类的遗传密码由大约30亿个DNA碱基组成，这些碱基是我们熟悉的DNA字母。但这些碱基中只有10%到15%构成了基因，而基因是细胞用来构建蛋白质的蓝图。在人类和其他许多生物体中，一些剩余的碱基序列发挥着至关重要的功能，比如帮助基因“开启”和“关闭”，以及将染色体连接在一起。然而，大部分DNA似乎根本没有明显的用途，导致一些人将其称为“垃圾”。这些“垃圾DNA”的一部分包括被称为DNA卫星的奇怪区域。这些是由四种DNA碱基——腺嘌呤(A)、胞嘧啶(C)、鸟嘌呤(G)和胸腺嘧啶(T)——的不同组合组成的重复序列，一遍又一遍地重复，就像遗传口吃一样。在过去的几年里，研究人员开始发现所谓的微卫星，即那些包含最短重复序列的卫星，其重要性与其大小不成比例，并具有各种显着的功能。事实上，科学家们正在发现，微型卫星的重复特性使它们特别容易在长度上增长或缩小，而这些变化对拥有它们的生物既有好的后果，也有坏的后果。例如，在某些致病细菌中，重复序列促进新特性的出现，使微生物能够在可能致命的环境变化中生存。一些微卫星也可能对人类产生重大影响，因为至少有10万个微卫星出现在人类基因组中，即人类细胞中DNA的完整补充。尽管迄今为止赋予人类微卫星的唯一功能是负面的——引起各种神经系统疾病——但微卫星可能是帮助塑造现代人类的进化过程中幸存下来的遗迹。当一些研究人员在寻找人类携带如此多重复DNA的原因时，许多人正在学习利用微卫星来诊断神经系统疾病，并识别有这些疾病风险的人。他们还发现，在某些癌症发展的早期，微卫星的长度会发生变化，这使它们成为早期癌症检测的有用标记物（见第98页方框）。由于微型卫星的长度因人而异，科学家们甚至开始用它们来识别罪犯和确定亲子关系——一种被称为DNA分析的程序
Ahuman’s genetic code consists of roughly three billion bases of DNA, the familiar “letters” of the DNA al-phabet. But a mere 10 to 15 percent of those bases make up genes, the blueprints cells use to build proteins. Some of the remaining base sequences in humans—and in many other organisms—perform crucial functions, such as helping to turn genes “on” and “off” and holding chromosomes together. Much of the DNA, however, seems to have no obvious purpose at all, leading some to refer to it as “junk.” Part of this “junk DNA” includes strange regions known as DNA satellites. These are repetitive sequences made up of various combinations of the four DNA bases—adenine (A), cytosine (C), guanine (G) and thymine (T)—repeated over and over, like a genetic stutter. In the past several years, researchers have begun to find that so-called microsatellites, those containing the shortest repeat sequences, have a significance disproportionately great for their size and perform a variety of remarkable functions.Indeed, scientists are discovering that the repetitive nature of microsatellites makes them particularly prone to grow or shrink in length and that these changes can have both good and bad consequences for the organisms that possess them. In certain disease-causing bacteria, for example, the repeat sequences promote the emergence of new properties that can enable the microbes to survive potentially lethal changes in the environment. Some microsatellites are also likely to have substantial effects in humans, because at least 100,000 occur in the human genome, the complete complement of DNA in a human cell. Although the only function assigned so far to human microsatellites is negative—causing a variety of neurological diseases—microsatellites may be surviving relics of evolutionary processes that helped to shape modern humans. While some investigators search for the reasons humans carry so much repetitive DNA, many are now learning to exploit microsatellites to diagnose neurological conditions and to identify people at risk for those disorders. They are also finding that microsatellites change in length early in the development of some cancers, making them useful markers for early cancer detection [see box on page 98]. And because the lengths of microsatellites may vary from one person to the next, scientists have even begun to use them to identify criminals and to determine paternity—a procedure known as DNA profiling