Forsdyke Donald R
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L3N6.
J Theor Biol. 2007 Oct 21;248(4):745-53. doi: 10.1016/j.jtbi.2007.07.008. Epub 2007 Jul 18.
The stability of a folded single-stranded nucleic acid depends on the composition and order of its constituent bases and may be assessed by taking into account the pairing energies of its constituent dinucleotides. To assess the possible biological significance of a computed structure, Maizel and coworkers in the 1980s compared the energy of folding of a natural single-stranded RNA sequence with the energies of several versions of the same sequence produced by shuffling base order. However, in the 2000s many took as self-evident the view that shuffling at the mononucleotide level (single bases) was conceptual wrong and should be replaced by shuffling at the level of dinucleotides (retaining pairs of adjacent bases). Folding energies then became indistinguishable from those of corresponding shuffled sequences and doubt was cast on the importance of secondary structures. Nevertheless, some continued productively to employ the single base shuffling approach, the justification for which is the topic of this paper. Because dinucleotide pairing energies are needed to calculate structure, it does not follow that shuffling should not disrupt dinucleotides. Base shuffling allows determination of the relative contributions of base composition and base order to total folding energy. The potential for secondary structure arises from pressures acting at both DNA and RNA levels, and is abundant throughout genomes-with a probable primary role in recombination. Within a gene the potential can often be accommodated, and base order and composition work together (values have the same negative sign) in contributing to total folding energy. But sometimes protein-coding pressure on base order conflicts with the pressure for secondary structure and the values have opposite signs. Total folding energy can be deemed of potential biological significance when the average of several readings is significantly less than zero.
折叠的单链核酸的稳定性取决于其组成碱基的成分和顺序，可通过考虑其组成二核苷酸的配对能量来评估。为了评估计算结构可能的生物学意义，20世纪80年代，梅泽尔及其同事将天然单链RNA序列的折叠能量与通过打乱碱基顺序产生的该序列的几个版本的能量进行了比较。然而，在21世纪，许多人认为在单核苷酸水平（单个碱基）上进行洗牌在概念上是错误的，应该被在二核苷酸水平（保留相邻碱基对）上进行洗牌所取代，这一观点是不言而喻的。然后，折叠能量变得与相应的洗牌序列的能量无法区分，人们对二级结构的重要性产生了怀疑。尽管如此，一些人仍继续有效地采用单碱基洗牌方法，本文的主题就是其合理性。因为计算结构需要二核苷酸配对能量，所以洗牌不一定会破坏二核苷酸。碱基洗牌可以确定碱基组成和碱基顺序对总折叠能量的相对贡献。二级结构的潜力源于在DNA和RNA水平上起作用的压力，并且在整个基因组中都很丰富——在重组中可能起主要作用。在一个基因内，这种潜力通常可以得到调节，碱基顺序和组成共同作用（值具有相同的负号）来贡献总折叠能量。但有时对碱基顺序的蛋白质编码压力与二级结构的压力相冲突，值具有相反的符号。当几个读数的平均值明显小于零时，总折叠能量可被视为具有潜在的生物学意义。
