Toomajian Christopher, Hu Tina T, Aranzana Maria José, Lister Clare, Tang Chunlao, Zheng Honggang, Zhao Keyan, Calabrese Peter, Dean Caroline, Nordborg Magnus
Molecular and Computational Biology, University of Southern California, Los Angeles, California, USA.
PLoS Biol. 2006 May;4(5):e137. doi: 10.1371/journal.pbio.0040137. Epub 2006 Apr 25.
The detection of footprints of natural selection in genetic polymorphism data is fundamental to understanding the genetic basis of adaptation, and has important implications for human health. The standard approach has been to reject neutrality in favor of selection if the pattern of variation at a candidate locus was significantly different from the predictions of the standard neutral model. The problem is that the standard neutral model assumes more than just neutrality, and it is almost always possible to explain the data using an alternative neutral model with more complex demography. Today's wealth of genomic polymorphism data, however, makes it possible to dispense with models altogether by simply comparing the pattern observed at a candidate locus to the genomic pattern, and rejecting neutrality if the pattern is extreme. Here, we utilize this approach on a truly genomic scale, comparing a candidate locus to thousands of alleles throughout the Arabidopsis thaliana genome. We demonstrate that selection has acted to increase the frequency of early-flowering alleles at the vernalization requirement locus FRIGIDA. Selection seems to have occurred during the last several thousand years, possibly in response to the spread of agriculture. We introduce a novel test statistic based on haplotype sharing that embraces the problem of population structure, and so should be widely applicable.
在遗传多态性数据中检测自然选择的痕迹对于理解适应的遗传基础至关重要，并且对人类健康具有重要意义。标准方法是，如果候选基因座处的变异模式与标准中性模型的预测有显著差异，就拒绝中性假设而支持选择。问题在于，标准中性模型假设的不止是中性，而且几乎总是可以用具有更复杂种群统计学特征的替代中性模型来解释数据。然而，如今丰富的基因组多态性数据使得完全摒弃模型成为可能，只需将候选基因座处观察到的模式与基因组模式进行比较，如果该模式极端就拒绝中性假设。在此，我们在真正的基因组规模上运用这种方法，将一个候选基因座与拟南芥基因组中的数千个等位基因进行比较。我们证明，选择作用增加了春化需求基因座FRIGIDA处早花等位基因的频率。选择似乎发生在过去几千年间，可能是对农业传播的响应。我们引入了一种基于单倍型共享的新型检验统计量，该统计量考虑了种群结构问题，因此应该具有广泛的适用性。
