Identifying and Classifying Shared Selective Sweeps from Multilocus Data
Identifying and Classifying Shared Selective Sweeps from Multilocus Data
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DOI：
10.1534/genetics.120.303137
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发表时间：
2020-05-01
期刊：
影响因子：
3.3
通讯作者：
DeGiorgio, Michael
中科院分区：
文献类型：
--
作者：
Harris, Alexandre M.;DeGiorgio, Michael
正选择导致有益等位基因的频率上升到高频率，导致选择性地扫描所选位点周围的多样性。因此，祖先群体中的选择性扫荡的特征可能仍然保留在其后代中。识别祖先中在其后代中共享的选择签名对于将扫描的时间置于上下文环境中是重要的，但很少有方法用于此目的。我们介绍了统计SS-H12，它可以识别基因组区域下共享的正选择跨种群，是基于预期的单倍型纯合性统计H12的理论，它检测最近的硬和软扫描的高频单倍型的存在。SS-H12与可比统计数据不同，因为它只需要至少两个群体，并正确识别和区分独立的收敛扫描和真正的祖先扫描，具有高功效和对各种人口统计模型的鲁棒性。此外，我们可以结合我们称为H2 Tot和H1 Tot的统计数据的比率来应用SS-H12，以进一步将所识别的共享扫描分类为硬扫描或软扫描。最后，我们从人类全基因组序列中鉴定了先前报道的和新的共享扫描候选者。先前报道的候选者包括印欧人的LCT和SLC 24 A5以及全球GPHN的特征良好的祖先扫描。新的候选人包括撒哈拉以南非洲人RGS 18的祖先扫描，参与调节血小板反应并与心脏性猝死有关，以及欧洲和东亚人群之间C2CD 5的会聚扫描，这可能解释了他们不同的胰岛素反应。
Positive selection causes beneficial alleles to rise to high frequency, resulting in a selective sweep of the diversity surrounding the selected sites. Accordingly, the signature of a selective sweep in an ancestral population may still remain in its descendants. Identifying signatures of selection in the ancestor that are shared among its descendants is important to contextualize the timing of a sweep, but few methods exist for this purpose. We introduce the statistic SS-H12, which can identify genomic regions under shared positive selection across populations and is based on the theory of the expected haplotype homozygosity statistic H12, which detects recent hard and soft sweeps from the presence of high-frequency haplotypes. SS-H12 is distinct from comparable statistics because it requires a minimum of only two populations, and properly identifies and differentiates between independent convergent sweeps and true ancestral sweeps, with high power and robustness to a variety of demographic models. Furthermore, we can apply SS-H12 in conjunction with the ratio of statistics we term H2Tot and H1Tot to further classify identified shared sweeps as hard or soft. Finally, we identified both previously reported and novel shared sweep candidates from human whole-genome sequences. Previously reported candidates include the well-characterized ancestral sweeps at LCT and SLC24A5 in Indo-Europeans, as well as GPHN worldwide. Novel candidates include an ancestral sweep at RGS18 in sub-Saharan Africans involved in regulating the platelet response and implicated in sudden cardiac death, and a convergent sweep at C2CD5 between European and East Asian populations that may explain their different insulin responses.