Compensatory neutral mutations and the evolution of RNA
Compensatory neutral mutations and the evolution of RNA
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DOI：
10.1023/a:1017059530664
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发表时间：
1998-01-01
期刊：
影响因子：
1.5
通讯作者：
Higgs, PG
中科院分区：
文献类型：
--
作者：
Higgs, PG
有许多RNA分子的例子，其中二级结构在进化过程中高度保守，但碱基序列保守性低得多，例如，转移RNA，核糖体RNA，和核糖核酸酶P。一个模型的补偿性中性突变在这里被用来描述在RNA螺旋的碱基序列的演变。有两个位点（即，一对的两侧），每个基因座上有四个等位基因（对应于A、C、G、U）。沃森-克里克碱基对（Au、CG、GC和UA）各自被分配适应度1，而所有其他对被视为错配并被分配适应度1-s。N个二倍体个体的群体被认为具有每个碱基u的突变率。对于生物学上合理的参数值，错配的频率总是很小，但四个匹配对的频率可以在很宽的范围内变化。使用扩散模型，计算四个匹配对中的任何一个的频率x的平稳分布。形状取决于变量β = 8 Nu（2）/9 s的组合。对于较小的β，分布在两个极端（x = 0和x = 1-z）处发散，其中z是不匹配的平均频率。总体通常几乎完全由四种类型的匹配对之一组成，但偶尔会在四种可能的状态之间发生变化。这里计算这些偏移发生的平均速率。两个基因座之间重组的影响是降低中间x处的概率密度，并增加极端处的权重。四种状态之间的转换速率因重组而减慢（如Kimura最初在具有不可逆突变的双等位基因模型中所示）。类似于u（2）/s的非常小的复合速率r足以显著增加跃迁之间的平均时间。除了它的应用RNA，这个模型也是相关的“平衡转移”理论描述的替代平衡之间的漂移的人口低健身谷。还计算了无限种群中不同等位基因组合频率的平衡值。结果表明，对于低复合率的平衡是对称的，但有一个临界复合率以上的替代不对称平衡变得稳定。
There are many examples of RNA molecules in which the secondary structure has been strongly conserved during evolution, but the base sequence is much less conserved, e.g., transfer RNA, ribosomal RNA, and ribonuclease P. A model of compensatory neutral mutations is used here to describe the evolution of the base sequence in RNA helices. There are two loci (i.e., the two sides of the pair) with four alleles at each locus (corresponding to A, C, G, U). Watson-Crick base pairs (AU, CG, GC, and UA) are each assigned a fitness 1, whilst all other pairs are treated as mismatches and assigned fitness 1-s. A population of N diploid individuals is considered with a mutation rate of u per base. For biologically reasonable parameter values, the frequency of mismatches is always small but the frequency of the four matching pairs can vary over a wide range. Using a diffusion model, the stationary distribution for the frequency x of any of the four matching pairs is calculated. The shape depends on the combination of variables beta = 8Nu(2)/9s. For small beta, the distribution diverges at the two extremes, x = 0 and x = 1-z, where z is the mean frequency of mismatches. The population typically consists almost entirely of one of the four types of matching pairs, but occasionally makes shifts between the four possible states. The mean rate at which these shifts occur is calculated here. The effect of recombination between the two loci is to decrease the probability density at intermediate x, and to increase the weight at the extremes. The rate of transition between the four states is slowed by recombination (as originally shown by Kimura in a two-allele model with irreversible mutation). A very small recombination rate r similar to u(2)/s is sufficient to increase the mean time between transitions dramatically. In addition to its application to RNA, this model is also relevant to the 'shifting balance' theory describing the drift of populations between alternative equilibria separated by low fitness valleys. Equilibrium values for the frequencies of the different allele combinations in an infinite population are also calculated. It is shown that for low recombination rates the equilibrium is symmetric, but there is a critical recombination rate above which alternative asymmetric equilibria become stable.