Marín Antonio, Xia Xuhua
Departamento de Genética, Universidad de Sevilla, Avenida Reina Mercedes 6, E-41012 Sevilla, Spain.
J Theor Biol. 2008 Aug 7;253(3):508-13. doi: 10.1016/j.jtbi.2008.04.004. Epub 2008 Apr 11.
The DNA strands in most prokaryotic genomes experience strand-biased spontaneous mutation, especially C-->T mutations produced by deamination that occur preferentially in the leading strand. This has often been invoked to account for the asymmetry in nucleotide composition, typically measured by GC skew, between the leading and the lagging strand. Casting such strand asymmetry in the framework of a nucleotide substitution model is important for understanding genomic evolution and phylogenetic reconstruction. We present a substitution model showing that the increased C-->T mutation will lead to positive GC skew in one strand but negative GC skew in the other, with greater C-->T mutation pressure associated with greater differences in GC skew between the leading and the lagging strand. However, the model based on mutation bias alone does not predict any positive correlation in GC skew between the leading and lagging strands. We computed GC skew for coding sequences collinear with the leading and lagging strands across 339 prokaryotic genomes and found a strong and positive correlation in GC skew between the two strands. We show that the observed positive correlation can be satisfactorily explained by an improved substitution model with one additional parameter incorporating a general trend of C avoidance.
大多数原核生物基因组中的DNA链会经历链偏向性自发突变，尤其是由脱氨基作用产生的C→T突变，这种突变优先发生在前导链上。这一点常被用来解释前导链和后随链之间核苷酸组成的不对称性，通常用GC偏斜来衡量。将这种链不对称性置于核苷酸替换模型的框架中，对于理解基因组进化和系统发育重建很重要。我们提出了一个替换模型，该模型表明增加的C→T突变会导致一条链出现正的GC偏斜，而另一条链则出现负的GC偏斜，C→T突变压力越大，前导链和后随链之间的GC偏斜差异就越大。然而，仅基于突变偏向的模型并不能预测前导链和后随链之间的GC偏斜存在任何正相关。我们计算了339个原核生物基因组中与前导链和后随链共线的编码序列的GC偏斜，发现两条链之间的GC偏斜存在很强的正相关。我们表明，通过一个改进的替换模型可以令人满意地解释观察到的正相关，该模型增加了一个参数，纳入了普遍的C回避趋势。
