THE EXON THEORY OF GENES
THE EXON THEORY OF GENES
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DOI：
10.1101/sqb.1987.052.01.098
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发表时间：
1987-01-01
期刊：
影响因子：
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通讯作者：
GILBERT, W
中科院分区：
文献类型：
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作者：
GILBERT, W
自从基因的内含子/外显子结构在10年前被发现以来（Berget et al.1977; Broker et al.1977），关于内含子的性质只出现了一些概括。大多数脊椎动物基因，但不是全部，具有内含子/外显子结构。外显子的长度分布相当窄，在约40或50个氨基酸处达到峰值。然而，内含子比外显子长一个数量级;它们的长度分布非常宽，最短的内含子只有50个碱基长，最长的内含子延伸到大约50，000bp。还没有发现一个基因需要所有内含子的存在才能发挥重要的功能。如果比较不同物种的基因，它们之间有足够的进化距离，同源基因的外显子序列漂移缓慢，编码氨基酸的位置是保守的，而内含子序列漂移的速度与第三个碱基位置一样快，表明它们在进化上是沉默的。尽管如此，由于内含子的长度和位置，内含子可能通过参与遗传重组并因此增加外显子作为独立元件重新排序的速率而发挥普遍作用。这就是外显子改组的概念（Blake 1978，1979，1983;吉尔伯特1978）。我们知道存在重组过程，可以在基因的相邻部分之间产生交换。这样的重组过程，通常被称为非法重组，将涉及DNA序列之间在几个匹配的碱基处的重组。一次这样的重组可以用来从一个简单的结构中产生一个双倍长度的基因;一次双重重组可以用来将一个基因的片段插入另一个基因中。在微生物中观察到这种重组。人类的一个例子是血红蛋白Lepore。然而，如果要重组的两个区域在完成的基因中被10，000个碱基的内含子分开，那么组合它们的非法重组不需要恰好发生在一个外显子的末端或恰好发生在第二个外显子的开始，而是发生在一个外显子末端之后10，000个碱基内或第二个外显子开始之前10，000个碱基内的任何地方。仅在组合的基础上，这种重组过程比涉及精确重组的过程快108倍。因此，内含子代表重组的热点;仅仅通过它们的存在和长度，它们就增加了重组的速率，从而增加了外显子的改组，增加了10 6或10 8倍。在这种模式下，
Since the intron/exon structure of genes was discovered 10 years ago (Berget et al. 1977; Broker et al. 1977), only a few generalities about the properties of introns have emerged. Most vertebrate genes, but not all, have an intron/exon structure. The length distribution of exons is rather narrow, peaking at about 40 or 50 amino acids. However, introns are an order of magnitude longer than the exons; their length distribution is very broad, the shortest introns being only 50 bases long, the longest extending out to some 50,000 bp. No essential function has been 1found that requires the presence of all the introns in a gene. If one compares genes from different species, separated by a sufficient evolutionary distance, the exon sequences of homologous genes drift slowly, the positions coding for amino acids being conserved, whereas the intron sequences drift as rapidly as third-base positions, indicating that they are evolutionarily silent. Nonetheless, there is a general role that introns might play, solely because of their length and position, by participating in genetic recombination and hence increasing the rate at which the exons reassort as independent elements. This is the concept of exon shuffling (Blake 1978, 1979, 1983; Gilbert 1978).The argument that introns increase the rate of recombination is straightforward. We know that there exist recombinational processes that can create interchanges between contiguous parts of a gene. Such recombinational processes, often called illegitimate recombination, would involve the recombination between DNA sequences at a few matched bases. A single such recombination could be used to make a double-length gene out of a simple structure; a double recombination might be used to insert a fragment of one gene into another. Such recombinations are observed in microorganisms. An example in humans is hemoglobin Lepore. However, if the two regions to be recombined were to be separated by a 10,000-base intron in the finished gene, the illegitimate recombination that combines them need not take place exactly at the end of one exon or exactly at the beginning of a second, but anywhere within 10,000 bases after the end of one exon or within 10,000 bases before the beginning of the second. On a combinatorial basis alone, this recombination process is 108 times more rapid than that involving exact recombination. Thus, the introns represent hot spots for recombination; by their mere presence and length they increase the rate of recombination, and hence shuffling of the exons, by factors of the order of 10 6 or 10 8. Under this model, the presence