FROM SEQUENCES TO SHAPES AND BACK - A CASE-STUDY IN RNA SECONDARY STRUCTURES
FROM SEQUENCES TO SHAPES AND BACK - A CASE-STUDY IN RNA SECONDARY STRUCTURES
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DOI：
10.1098/rspb.1994.0040
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发表时间：
1994-03-22
影响因子：
4.7
通讯作者：
HOFACKER, IL
中科院分区：
文献类型：
--
作者：
SCHUSTER, P;FONTANA, W;HOFACKER, IL
RNA折叠在这里被视为将二级结构分配给序列的映射。在固定链长时，序列的数量远远超过结构的数量。结构的频率是高度不均匀的，遵循齐夫定律的一般形式：我们发现相对较少的常见频率和许多罕见的频率。利用逆折叠算法，我们证明了具有相同结构的序列在序列空间上是随机分布的。所有常见的结构都可以通过许多比链长小得多的突变从任意序列中获得。序列空间由广泛的神经网络渗透，该网络将最近的邻居折叠成相同的结构。对于进化适应和应用分子进化的影响是显而易见的：通过突变和选择找到特定的结构比预期的要简单得多，即使催化活性在RNA结构空间中被证明是稀疏的，进化过程也很难错过它。
RNA folding is viewed here as a map assigning secondary structures to sequences. At fixed chain length the number of sequences far exceeds the number of structures. Frequencies of structures are highly non-uniform and follow a generalized form of Zipf's law: we find relatively few common and many rare ones. By using an algorithm for inverse folding, we show that sequences sharing the same structure are distributed randomly over sequence space. All common structures can be accessed from an arbitrary sequence by a number of mutations much smaller than the chain length. The sequence space is percolated by extensive neutral networks connecting nearest neighbours folding into identical structures. Implications for evolutionary adaptation and for applied molecular evolution are evident: finding a particular structure by mutation and selection is much simpler than expected and, even if catalytic activity should turn out to be sparse in the space of RNA structures, it can hardly be missed by evolutionary processes.