Substitution Patterns Are GC-Biased in Divergent Sequences across the Metazoans
Substitution Patterns Are GC-Biased in Divergent Sequences across the Metazoans
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DOI：
10.1093/gbe/evr051
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发表时间：
2011-01-01
影响因子：
3.3
通讯作者：
Pollard, Katherine S.
中科院分区：
文献类型：
--
作者：
Capra, John A.;Pollard, Katherine S.
人类和黑猩猩基因组中进化最快的区域显示出明显过量的弱（A，T）到强（G，C）核苷酸取代，因为与它们的共同祖先不同。我们使用最近测序的八个真核物种的基因组和重组图谱研究了发散序列 (BDS) 中这种弱到强 (W -> S) 偏差的系统发育程度和可能原因。为了量化 BDS 的证据，我们使用有效的最大似然方法和上下文相关的进化模型来推断替代历史。然后，我们根据染色体上的 W -> S 偏差和密度注释了所有谱系特异性替换。最后，我们使用推断的替代来计算 BDS 分数（替代类型和密度之间的对数优势比），并使用 Fisher 精确检验评估其统计显着性。应用这种方法，我们在人类、小鼠、狗、刺鱼、果蝇和蠕虫的编码和非编码序列中发现了显着的 BDS。我们还观察到鸡肉和酵母中 W -> S BDS 显着缺乏。 BDS 分数在物种之间以及每个物种内的染色体上有所不同。它与不同物种的不同基因组特征密切相关，但在几个物种中也发现与重组率有很强的相关性。我们的结果表明，快速进化序列中的 W -> S 替换偏差是一种普遍现象。观察到的 BDS 模式表明，与重组相关的过程，例如 GC 偏向的基因转换，参与了许多物种中偏向的产生，但 BDS 的强度可能取决于许多因素，包括基因组稳定性、重组率随时间和整个基因组的变异性、减数分裂的频率以及每个物种的异交量。
The fastest-evolving regions in the human and chimpanzee genomes show a remarkable excess of weak (A,T) to strong (G,C) nucleotide substitutions since divergence from their common ancestor. We investigated the phylogenetic extent and possible causes of this weak to strong (W -> S) bias in divergent sequences (BDS) using recently sequenced genomes and recombination maps from eight trios of eukaryotic species. To quantify evidence for BDS, we inferred substitution histories using an efficient maximum likelihood approach with a context-dependent evolutionary model. We then annotated all lineage-specific substitutions in terms of W -> S bias and density on the chromosomes. Finally, we used the inferred substitutions to calculate a BDS score-a log odds ratio between substitution type and density-and assessed its statistical significance with Fisher's exact test. Applying this approach, we found significant BDS in the coding and noncoding sequence of human, mouse, dog, stickleback, fruit fly, and worm. We also observed a significant lack of W -> S BDS in chicken and yeast. The BDS score varies between species and across the chromosomes within each species. It is most strongly correlated with different genomic features in different species, but a strong correlation with recombination rates is found in several species. Our results demonstrate that a W -> S substitution bias in fast-evolving sequences is a widespread phenomenon. The patterns of BDS observed suggest that a recombination-associated process, such as GC-biased gene conversion, is involved in the production of the bias in many species, but the strength of the BDS likely depends on many factors, including genome stability, variability in recombination rate over time and across the genome, the frequency of meiosis, and the amount of outcrossing in each species.