Schuster P, Fontana W, Stadler P F, Hofacker I L
Institut für Molekulare Biotechnologie, Jena, Germany.
Proc Biol Sci. 1994 Mar 22;255(1344):279-84. doi: 10.1098/rspb.1994.0040.
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 of RNA structures, it can hardly be missed by evolutionary processes.
在这里，RNA折叠被视为一种将二级结构分配给序列的映射。在固定链长下，序列的数量远远超过结构的数量。结构的频率高度不均匀，遵循齐普夫定律的广义形式：我们发现相对较少的常见结构和许多罕见结构。通过使用反向折叠算法，我们表明共享相同结构的序列在序列空间中随机分布。通过比链长小得多的突变数量，可以从任意序列访问所有常见结构。序列空间由连接折叠成相同结构的最近邻的广泛中性网络渗透。对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结构比预期的要简单得多，而且，即使催化活性在RNA结构中应该是稀少的，进化过程也很难错过它。
