Center for Biomolecular Science and Engineering, University of California, Santa Cruz, USA.
Genome Biol Evol. 2011;3:614-26. doi: 10.1093/gbe/evr058. Epub 2011 Jun 21.
Fast evolving regions of many metazoan genomes show a bias toward substitutions that change weak (A,T) into strong (G,C) base pairs. Single-nucleotide polymorphisms (SNPs) do not share this pattern, suggesting that it results from biased fixation rather than biased mutation. Supporting this hypothesis, analyses of polymorphism in specific regions of the human genome have identified a positive correlation between weak to strong (W→S) SNPs and derived allele frequency (DAF), suggesting that SNPs become increasingly GC biased over time, especially in regions of high recombination. Using polymorphism data generated by the 1000 Genomes Project from 179 individuals from 4 human populations, we evaluated the extent and distribution of ongoing GC-biased evolution in the human genome. We quantified GC fixation bias by comparing the DAFs of W→S mutations and S→W mutations using a Mann-Whitney U test. Genome-wide, W→S SNPs have significantly higher DAFs than S→W SNPs. This pattern is widespread across the human genome but varies in magnitude along the chromosomes. We found extreme GC-biased evolution in neighborhoods of recombination hot spots, a significant correlation between GC bias and recombination rate, and an inverse correlation between GC bias and chromosome arm length. These findings demonstrate the presence of ongoing fixation bias favoring G and C alleles throughout the human genome and suggest that the bias is caused by a recombination-associated process, such as GC-biased gene conversion.
许多后生动物基因组的快速进化区域表现出一种偏向，即碱基替换将较弱的（A，T）转换为较强的（G，C）碱基对。单核苷酸多态性（SNP）没有表现出这种模式，这表明它是由偏向固定而不是偏向突变引起的。支持这一假说，对人类基因组特定区域的多态性分析表明，弱至强（W→S）SNP 与衍生等位基因频率（DAF）之间存在正相关关系，这表明随着时间的推移，SNP 变得越来越偏向 GC，尤其是在高重组区域。利用来自 4 个人类群体的 179 个人的 1000 基因组计划产生的多态性数据，我们评估了人类基因组中正在进行的 GC 偏向进化的程度和分布。我们通过使用曼-惠特尼 U 检验比较 W→S 突变和 S→W 突变的 DAF 来量化 GC 固定偏向。在全基因组范围内，W→S SNP 的 DAF 明显高于 S→W SNP。这种模式在人类基因组中广泛存在，但在染色体上的幅度不同。我们在重组热点附近发现了极端的 GC 偏向进化，GC 偏向与重组率之间存在显著相关性，GC 偏向与染色体臂长度之间存在负相关性。这些发现表明，整个人类基因组中存在持续的固定偏向，有利于 G 和 C 等位基因，并且表明这种偏向是由与重组相关的过程引起的，例如 GC 偏向性基因转换。
