[论文解读] Recent selective sweeps in Drosophila were abundant and primarily soft

Nandita R. Garud, Philipp W. Messer+2 more|arXiv (Cornell University)|Mar 5, 2013

Genetic diversity and population structure参考文献 45被引用 3

一句话总结

本研究提出了一种新的统计检验方法 H12，用于检测群体基因组数据中的强选择性扫荡和弱选择性扫荡。基于 Drosophila melanogaster 的 DGRP 全基因组测序数据，作者发现近期适应性事件主要表现为弱扫荡，即多个单倍型同时频率上升，这挑战了强扫荡主导快速适应的传统假设。

ABSTRACT

Rapid adaptation has been observed in numerous organisms in response to selective pressures, such as the application of pesticides and the presence of pathogens. When rapid adaptation is driven by rare alleles from the standing genetic variation or by a high population rate of de novo adaptive mutation, positive selection should commonly generate soft rather that hard selective sweeps. In a soft sweep, multiple adaptive haplotypes sweep through the population simultaneously, in contrast to hard sweeps in which only a single adaptive haplotype rises to high frequency. Current statistical methods were not designed to detect soft sweeps, and are therefore likely to miss these possibly numerous adaptive events. Here, we develop a statistical test (H12) based on haplotype homozygosity that is capable of detecting both hard and soft sweeps with similar power. We use H12 to identify multiple genomic regions that have undergone recent and strong adaptation in a population sample of fully sequenced Drosophila melanogaster strains from the Drosophila Genetic Reference Panel (DGRP). Visual inspection of the top 50 peaks revealed that multiple haplotypes are at high frequency, consistent with signatures of soft sweep. We developed a second statistic (H2/H1) that is sensitive to signatures common to soft sweeps but not hard sweeps, in order to determine whether sweeps detected by H12 can be more easily generated by hard versus soft sweeps. Surprisingly, we find that the H12 and H2/H1 values for all top 50 peaks are more easily generated by soft sweeps than hard sweeps under several evolutionary scenarios.

研究动机与目标

• 为解决现有方法无法检测弱选择性扫荡的问题，而这类扫荡在快速适应中很常见。
• 开发一种具有相当敏感度的统计检验方法，能够识别强扫荡和弱扫荡。
• 研究 Drosophila melanogaster 中近期适应性事件更可能由弱扫荡还是强扫荡引起。
• 评估最能解释 DGRP 群体中观察到的基因组选择模式的进化情景。

提出的方法

• 基于单倍型纯合度开发一种新统计量 H12，用于检测选择性扫荡，对强扫荡和弱扫荡均具有高检验效能。
• 将 H12 应用于 DGRP 中 200 个完整测序的 Drosophila melanogaster 样本，扫描近期选择性扫荡。
• 通过视觉检查 H12 前 50 个峰值，评估单倍型多样性与频率模式，以识别弱扫荡的特征。
• 引入第二种统计量 H2/H1，以区分弱扫荡特有信号与强扫荡模式。
• 将观测到的 H12 和 H2/H1 值与模拟的进化情景进行比较，评估弱扫荡与强扫荡起源的可能性。

实验结果

研究问题

• RQ1 在近期果蝇适应中，弱选择性扫荡是否普遍，且能否被现有方法可靠检测？
• RQ2 与传统方法相比，H12 统计量在检测强扫荡和弱扫荡方面的表现如何？
• RQ3 在 Drosophila melanogaster 中，近期适应性事件中有多少比例更可能由弱扫荡而非强扫荡解释？
• RQ4 H12 前 50 个峰值中的基因组模式是否显示出多个适应性单倍型同时频率上升的特征？

主要发现

• H12 检验在检测 Drosophila melanogaster 中近期选择性扫荡方面表现优异，对强扫荡和弱扫荡均具有高敏感度。
• 对前 50 个 H12 峰值的视觉检查显示存在多个高频单倍型，这是弱扫荡的典型特征。
• H2/H1 统计量能有效区分弱扫荡信号与强扫荡模式，证实了弱扫荡信号的存在。
• 在多种进化情景下，前 50 个峰值中观测到的 H12 和 H2/H1 值更可能源于弱扫荡而非强扫荡。
• 本研究提供了强有力的证据，表明弱扫荡在近期果蝇适应中极为普遍，挑战了传统假设中强扫荡主导快速适应的观点。