Zull J E, Taylor R C, Michaels G S, Rushforth N B
Department of Biology, Case Western Reserve University, Cleveland, OH 44106.
Nucleic Acids Res. 1994 Aug 25;22(16):3373-80. doi: 10.1093/nar/22.16.3373.
We have asked whether coding segments of nucleic acids generate amino acid sequences which have an antisense relationship to other amino acid sequences in the same chain (i.e. 'Internal Antisense'), and if so, could the internal antisense content be related to the structure of the encoded protein? Computer searches were conducted with the coding sequences for 132 proteins. The result for each search of a specific sequence was compared to the mean result obtained from 1000 randomly assembled nucleic acid chains whose length and base composition were identical to that of the native sequences. The study was conducted in all three reading frames. The normal reading frame (frame one) was found to be contain lower amounts of internal antisense than the randomly assembled chains, whereas the frame two results were much higher. The internal antisense content in frame three was not significantly different from that in the random chains. The amount of internal antisense in frames two and three was correlated with the GC content at the center position of the codons in that frame, but this correlation was absent in frame one. No correlation with chain length was found. Qualitatively similar results were obtained when the random model was limited to retain the same purine/pyrimidine ratio as the native chains at each position in the codons, but in this case the internal antisense in frame three was also significantly greater than the computer-generated sequences. The results suggest that the internal antisense content in the correct reading frame has a qualitatively different origin from that in the other two frames. The high amount in frames two and three is apparently an artifact resulting from the asymmetric distribution of G and C in the codons, while the low amount in frame one may suggest evolutionary selection against internal antisense. Thus, the results do not support a relationship between internal antisense and protein structure.
我们曾提出疑问，核酸的编码片段是否会生成与同一条链上的其他氨基酸序列具有反义关系的氨基酸序列（即“内部反义”），如果是这样，内部反义含量是否与编码蛋白质的结构有关？我们对132种蛋白质的编码序列进行了计算机搜索。每次对特定序列的搜索结果都与从1000条随机组装的核酸链中获得的平均结果进行比较，这些核酸链的长度和碱基组成与天然序列相同。该研究在所有三个阅读框中进行。发现正常阅读框（第一框）中的内部反义含量低于随机组装的链，而第二框的结果则高得多。第三框中的内部反义含量与随机链中的没有显著差异。第二框和第三框中的内部反义含量与该框中密码子中心位置的GC含量相关，但第一框中不存在这种相关性。未发现与链长相关。当随机模型被限制为在密码子的每个位置保持与天然链相同的嘌呤/嘧啶比时，获得了定性相似的结果，但在这种情况下，第三框中的内部反义也明显大于计算机生成的序列。结果表明，正确阅读框中的内部反义含量与其他两个框中的来源在性质上不同。第二框和第三框中的高含量显然是密码子中G和C不对称分布导致的假象，而第一框中的低含量可能表明对内部反义的进化选择。因此，结果不支持内部反义与蛋白质结构之间的关系。
