[论文解读] Genome Sequencing Highlights Genes Under Selection and the Dynamic Early History of Dogs

Adam H. Freedman, Rena M. Schweizer+28 more|arXiv (Cornell University)|May 31, 2013

Genomics and Phylogenetic Studies被引用 5

一句话总结

本研究利用狼、狗及赤狐的高覆盖度全基因组测序，重建了狗驯化的动态早期历史。研究揭示狗经历了严重的种群瓶颈（有效种群大小减少17至49倍），狗与狼在分化后存在基因流，驯化时间约为11,000至16,000年前，早于农业的出现；且无现代狼谱系与狗密切相关，提示其起源复杂，需重新评估以往假说。

ABSTRACT

To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we analyzed novel high-quality genome sequences of three gray wolves, one from each of three putative centers of dog domestication, two ancient dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. We find dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow, which confounds previous inferences of dog origins. In dogs, the domestication bottleneck was severe involving a 17 to 49-fold reduction in population size, a much stronger bottleneck than estimated previously from less intensive sequencing efforts. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was far larger than represented by modern wolf populations. Conditional on mutation rate, we narrow the plausible range for the date of initial dog domestication to an interval from 11 to 16 thousand years ago. This period predates the rise of agriculture, implying that the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that surprisingly, none of the extant wolf lineages from putative domestication centers are more closely related to dogs, and the sampled wolves instead form a sister monophyletic clade. This result, in combination with our finding of dog-wolf admixture during the process of domestication, suggests a re-evaluation of past hypotheses of dog origin is necessary. Finally, we also detect signatures of selection, including evidence for selection on genes implicated in morphology, metabolism, and neural development. Uniquely, we find support for selective sweeps at regulatory sites suggesting gene regulatory changes played a critical role in dog domestication.

研究动机与目标

• 利用高覆盖度基因组测序识别狗驯化过程中潜在的遗传变化。
• 重建狗与狼的动态早期演化历史，包括种群瓶颈与基因流。
• 通过分析多个狼谱系与古代狗样本，解决关于狗地理起源的矛盾假说。
• 检测狗中与形态、代谢及神经发育相关基因的阳性选择信号。
• 通过识别非编码区域的清除选择，评估调控变化在驯化中的作用。

提出的方法

• 对三个疑似驯化中心的灰狼、两条古代狗谱系（巴辛吉犬与澳洲野犬）及一只赤狐进行高覆盖度全基因组测序，作为外群。
• 通过系统发育分析推断狗与狼谱系之间的进化关系及分化时间。
• 通过群体遗传建模估算狗与狼的有效种群大小，并检测其中的瓶颈事件。
• 利用FST与iHS统计量检测清除选择，识别狗中处于正向选择的区域。
• 通过D统计量与Dsuite分析推断狗与狼谱系之间的基因流。
• 利用突变率校准对驯化事件进行条件性定年，以缩小狗与狼分化时间窗口。

实验结果

研究问题

• RQ1 狗与狼的分化时间是什么？这一时间是否早于农业的出现？
• RQ2 哪些现代狼种群与祖先狗谱系关系最近？它们是否反映了驯化的真正地理起源？
• RQ3 狗与狼的种群历史如何，特别是种群瓶颈与基因流方面？
• RQ4 哪些基因或调控区域在狗驯化过程中显示出阳性选择的信号？
• RQ5 与编码突变相比，调控变化在驯化狗表型变化中起到了多大程度的贡献？

主要发现

• 狗经历了严重的种群瓶颈，有效种群大小减少了17至49倍，表明其瓶颈强度远超以往估计。
• 狼在与狗分化后不久也经历了剧烈的瓶颈，提示祖先狗种群可能源自比现代狼更具遗传多样性的狼谱系。
• 狗驯化的初始时间被精确限定在11,000至16,000年前，早于农业的兴起，暗示狩猎采集社会可能在早期驯化中发挥了作用。
• 来自疑似驯化中心的任何现代狼谱系，均未比其他狼种群更接近狗，挑战了以往关于地理起源的假说。
• 在与形态、代谢及神经发育相关的基因中检测到阳性选择信号，且在调控区域存在强有力的清除选择证据。
• 检测到狗与狼谱系之间的分化后基因流，干扰了以往的推断，表明驯化过程复杂且动态。