Computer Simulation of SNP Accrual in the Setting of a Transition Bias Leads to Enhancement of Synonymous Variants.

SNPs were placed randomly at computer-generated positions in the full-length CFTR sequence, or in a GC-rich region (150 base pair interval (4260–4409) of the human CFTR open reading frame) in an unbiased fashion, or with a transition bias according to the CFTR mutation database (see Table 2), or transition bias observed for either exonic or intronic SNPs from 1000 Genomes (Table 1). GC rich isochores are reported to be more likely sites of natural mutation. The ratio of resulting non-synonymous (N) to synonymous (S) SNPs is shown. The data indicates strong preference for synonymous variants in the setting of transition bias, although magnitude of the effect does not fully account for enhancement of synonymous SNPs shown in Figure 2. Transition bias may therefore represent one (perhaps among several) evolutionary mechanisms serving to augment formation of synonymous DNA polymorphism.Computer Simulation of SNP Accrual in the Setting of a Transition Bias Leads to Enhancement of Synonymous Variants.

单核苷酸多态性（Single Nucleotide Polymorphisms，SNPs）可被设置为以下四种情形：一是随机分布于计算机生成的全长囊性纤维化跨膜传导调节因子（Cystic Fibrosis Transmembrane Conductance Regulator，CFTR）序列位点中；二是以无偏倚方式定位于高GC区域（GC-rich region，即人类CFTR开放阅读框（open reading frame）的150碱基对区间4260–4409）；三是依据CFTR突变数据库（见表2）引入转换偏倚（transition bias）；四是采用千人基因组计划（1000 Genomes）中外显子或内含子SNPs所观测到的转换偏倚。已有研究表明，高GC等容区更易发生自然突变。本研究展示了所得非同义（N）与同义（S）SNPs的比值。数据显示，在转换偏倚条件下，同义变异体存在显著偏好性，但该效应的强度并未完全解释图2中同义SNPs的富集现象。因此，转换偏倚可能是促进同义DNA多态性形成的进化机制之一（或许为多种机制中的一种）。在转换偏倚条件下开展的SNPs积累计算机模拟可导致同义变异体的富集。