Background Selection as Baseline for Nucleotide Variation across the Drosophila Genome
Background Selection as Baseline for Nucleotide Variation across the Drosophila Genome
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DOI：
10.1371/journal.pgen.1004434
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发表时间：
2014-06-01
期刊：
影响因子：
4.5
通讯作者：
Comeron, Josep M.
中科院分区：
文献类型：
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作者：
Comeron, Josep M.
自然选择对有害突变的不断去除，导致基因连锁位点的中性多样性和选择效力的减少（这一过程称为背景选择，BGS）。然而，群体遗传学研究在调查人口统计事件或其他类型选择的存在时，往往忽略了BGS的影响。为了获得包含有害突变不可避免的后果的更现实的进化预期，我们在独立于多态性数据的BGS情景下生成了黑腹果蝇基因组的高分辨率变异景观。我们发现BGS在形成整个基因组的变异水平方面起着重要作用，包括长内含子和远离注释基因的基因间区域。我们还发现，在观察到的常染色体多样性差异中，有很大一部分可以单独用BGS来解释，在100 kb的尺度上，单个染色体臂的差异高达70%，这表明BGS的预测可以用作推断其他类型的选择和人口统计学事件的基线。这种方法允许用最近自适应事件和选择性扫描的信号检测几个异常区域。然而，BGS基线的使用特别适合于研究平衡选择的存在，我们的研究揭示了许多基因组区域，当考虑到BGS背景时，其预测特征比预期的多态性更高。重要的是，我们证明了这些结论对BGS模型的突变和选择参数具有鲁棒性。最后，对蛋白质进化的分析以及之前对果蝇物种之间遗传图谱的比较表明，重组景观在时间上是可变的，因此，局部的BGS效应可能在现存和过去的阶段有所不同。由于全基因组BGS和连锁效应的时间变化可能会影响估计人口统计学和选择性事件的方法，因此未来的分析应纳入BGS预测，并捕获跨基因组和沿谱系的局部重组变异。
The constant removal of deleterious mutations by natural selection causes a reduction in neutral diversity and efficacy of selection at genetically linked sites (a process called Background Selection, BGS). Population genetic studies, however, often ignore BGS effects when investigating demographic events or the presence of other types of selection. To obtain a more realistic evolutionary expectation that incorporates the unavoidable consequences of deleterious mutations, we generated high-resolution landscapes of variation across the Drosophila melanogaster genome under a BGS scenario independent of polymorphism data. We find that BGS plays a significant role in shaping levels of variation across the entire genome, including long introns and intergenic regions distant from annotated genes. We also find that a very large percentage of the observed variation in diversity across autosomes can be explained by BGS alone, up to 70% across individual chromosome arms at 100-kb scale, thus indicating that BGS predictions can be used as baseline to infer additional types of selection and demographic events. This approach allows detecting several outlier regions with signal of recent adaptive events and selective sweeps. The use of a BGS baseline, however, is particularly appropriate to investigate the presence of balancing selection and our study exposes numerous genomic regions with the predicted signature of higher polymorphism than expected when a BGS context is taken into account. Importantly, we show that these conclusions are robust to the mutation and selection parameters of the BGS model. Finally, analyses of protein evolution together with previous comparisons of genetic maps between Drosophila species, suggest temporally variable recombination landscapes and, thus, local BGS effects that may differ between extant and past phases. Because genome-wide BGS and temporal changes in linkage effects can skew approaches to estimate demographic and selective events, future analyses should incorporate BGS predictions and capture local recombination variation across genomes and along lineages.