Ornston L N, Yeh W K
Proc Natl Acad Sci U S A. 1979 Aug;76(8):3996-4000. doi: 10.1073/pnas.76.8.3996.
Recurring patterns of primary structure have been observed in enzymes that mediate sequential metabolic reactions in bacteria. The enzymes, muconolactone Delta-isomerase [(+)-4-hydroxy-4-carboxymethylisocrotonolactone Delta(2)-Delta(3)-isomerase, EC 5.3.3.4] and beta-ketoadipate enol-lactone hydrolase [4-carboxymethylbut-3-enolide(1,4)enol-lactone-hydrolase, EC 3.1.1.24], have been coselected in bacterial populations because the isomerase can confer no nutritional advantage in the absence of the hydrolase. Similar amino acid sequences recur within the structure of the isomerase, and the amino-terminal amino acid sequence of the isomerase from Pseudomonas putida appears to be evolutionarily homologous with the corresponding sequence of a beta-ketoadipate enol-lactone hydrolase from Acinetobacter calcoaceticus. One interpretation of the sequence repetitions is that they reflect tandem duplication mutations that took place early in the evolution of the proteins. According to this view, the mutations caused elongation of structural genes and the creation of duplicated genes as the metabolic pathways evolved. A review of the sequence data calls attention to a different hypothesis: repeated amino acid sequences were introduced in the course of the proteins' evolution by substitution of copies of DNA sequences into structural genes. Our observations are interpreted on the basis of a model proposing genetic exchange between misaligned DNA sequences. The model predicts that misalignments in one chromosomal region can influence the nature of mutations in another region. Thus, as often has been observed, the mutability of a base pair will be determined by its location in a DNA sequence. Furthermore, the intrachromosomal recombination of DNA sequences may account for complex genetic modifications that occur as new pathways evolve. The model provides an interpretation of an apparent paradox, the rapid creation of new metabolic traits by bacterial genomes that are remarkably resistant to genetic drift.
在介导细菌中连续代谢反应的酶中观察到了一级结构的重复模式。这些酶，粘康酸内酯δ-异构酶[（+）-4-羟基-4-羧甲基异巴豆酸内酯δ（2）-δ（3）-异构酶，EC 5.3.3.4]和β-酮己二酸烯醇内酯水解酶[4-羧甲基丁-3-烯醇化物（1,4）烯醇内酯水解酶，EC 3.1.1.24]，在细菌群体中是共同选择的，因为在没有水解酶的情况下，异构酶不会赋予营养优势。相似的氨基酸序列在异构酶的结构中反复出现，恶臭假单胞菌异构酶的氨基末端氨基酸序列似乎与乙酸钙不动杆菌β-酮己二酸烯醇内酯水解酶的相应序列在进化上是同源的。对序列重复的一种解释是，它们反映了在蛋白质进化早期发生的串联重复突变。根据这种观点，随着代谢途径的进化，这些突变导致结构基因的延长和重复基因的产生。对序列数据的回顾引起了人们对另一种假说的关注：在蛋白质进化过程中，通过将DNA序列的拷贝替换到结构基因中引入了重复的氨基酸序列。我们的观察结果是基于一个提出错配DNA序列之间遗传交换的模型来解释的。该模型预测，一个染色体区域的错配可以影响另一个区域突变的性质。因此，正如经常观察到的那样，一个碱基对的突变性将由其在DNA序列中的位置决定。此外，DNA序列的染色体内重组可能解释了随着新途径的进化而发生的复杂遗传修饰。该模型解释了一个明显的悖论，即细菌基因组能够快速创造新的代谢特征，同时又对遗传漂变具有显著的抗性。
