Modeling the spatiotemporal spread of beneficial alleles using ancient genomes.
Modeling the spatiotemporal spread of beneficial alleles using ancient genomes.
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DOI：
10.7554/elife.73767
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发表时间：
2022-12-20
期刊：
影响因子：
7.7
通讯作者：
Racimo F
中科院分区：
文献类型：
--
作者：
Muktupavela RA;Petr M;Ségurel L;Korneliussen T;Novembre J;Racimo F
古代基因组测序技术现在提供了前所未有的详细研究自然选择的机会。我们可以直接观察到，在过去1万年的人类历史中，在世界上的某个特定地区，某个特定的等位基因是否存在，而不是根据选择在当今基因组中留下的间接足迹进行推断。使用古代基因组研究选择的方法通常依赖于将个体划分为离散的时间段或世界区域。然而，对自然选择的完整理解需要更细致的统计方法，这些方法可以明确地模拟等位基因频率在空间和时间上的连续变化。在这里，我们介绍了一种方法来推断一个有益的等位基因的传播在景观使用二维偏微分方程。与以前的方法不同，我们的框架可以处理带有时间戳的古代样本，以及来自低覆盖率基因组的基因型可能性和伪单倍体序列。我们将该方法应用于一组已发表的古代西欧亚基因组，以产生动态地图，展示候选有益等位基因在时间和空间上的推断传播。我们还提供了这些等位基因的选择和扩散率的强度估计。最后，我们强调了在更复杂的情况下准确追踪有益等位基因传播的可能改进途径。分析我们古代祖先的基因组可以揭示某些特征在进化过程中如何在人类群体中传播。使个体更好地适应环境的突变更有可能传递给下一代，并变得更加普遍。例如，随着时间的推移，一种使成年人能够消化乳制品中的糖的遗传变异在人类中变得越来越普遍。然而，进化不仅跨越时间发生：它也跨越空间。使用现有的方法对这种基因突变的地理分布进行建模是具有挑战性的。为了克服这一点，Muktupavela等人开发了一种新的计算方法，该方法使用现代和古代人类基因组来研究特定遗传变异在空间和时间上的进化。该工具可以确定某些变种首先出现的位置、它们在地理区域中传播的速度以及它们在人群中流行的速度。Muktupavela等人应用他们的新方法，该方法基于先前发表的框架，跟踪两种常见遗传变异的传播，这些遗传变异先前被报道受到自然选择的影响：一种允许成年人消化乳制品，另一种与皮肤色素沉着有关。他们发现，使乳制品消费成为可能的突变起源于现在的俄罗斯西南部或乌克兰东部。这种变异随后向西扩散，在全新世变得越来越普遍。与皮肤色素沉着有关的突变比与乳制品有关的突变出现得更靠南，然后也向西传播。新石器时代和青铜时代的大规模人类迁徙可能有助于分散这两种变体。Muktupavela等人开发的模型可以帮助科学家追踪人类群体中其他遗传变异的地理分布，并为人类如何适应不断变化的环境条件提供新的见解。将大规模迁移或冰川退缩等重大事件纳入模型中，可能会带来更多的见解。
Ancient genome sequencing technologies now provide the opportunity to study natural selection in unprecedented detail. Rather than making inferences from indirect footprints left by selection in present-day genomes, we can directly observe whether a given allele was present or absent in a particular region of the world at almost any period of human history within the last 10,000 years. Methods for studying selection using ancient genomes often rely on partitioning individuals into discrete time periods or regions of the world. However, a complete understanding of natural selection requires more nuanced statistical methods which can explicitly model allele frequency changes in a continuum across space and time. Here we introduce a method for inferring the spread of a beneficial allele across a landscape using two-dimensional partial differential equations. Unlike previous approaches, our framework can handle time-stamped ancient samples, as well as genotype likelihoods and pseudohaploid sequences from low-coverage genomes. We apply the method to a panel of published ancient West Eurasian genomes to produce dynamic maps showcasing the inferred spread of candidate beneficial alleles over time and space. We also provide estimates for the strength of selection and diffusion rate for each of these alleles. Finally, we highlight possible avenues of improvement for accurately tracing the spread of beneficial alleles in more complex scenarios. Analyzing the genomes of our ancient ancestors can reveal how certain traits spread through the human population over the course of evolution. Mutations that make individuals better equipped to survive their environment are more likely to be passed on to the next generation and become more common. For example, a genetic variant that enables adult people to digest sugars in dairy products has become more common in humans over time. Yet evolution does not only happen across time: it transverses space as well. Modeling the geographic spread of such genetic mutations is challenging using existing methods. To overcome this, Muktupavela et al. developed a new computational method that uses modern and ancient human genomes to study the evolution of specific genetic variants across space and time. The tool can determine where certain variants first emerged, how quickly they spread across geographic areas, and how rapidly they became prevalent in human populations. Muktupavela et al. applied their new method, which was based on a previously published framework, to track the spread of two common genetic variations that have previously been reported to be subject to natural selection: one that allows adult humans to digest dairy products, and another associated with skin pigmentation. They found that the mutation that enabled dairy consumption originated around what is now southwestern Russia or eastern Ukraine. The variation then spread westward, becoming increasingly more common over the course of the Holocene. The mutation related to skin pigmentation emerged further south than the dairy-related variation, and then also spread westward. Massive human migrations during the Neolithic and Bronze Age eras may have helped disperse both variants. The model developed by Muktupavela et al. could help scientists track the geographic spread of other genetic variants in human populations, as well as provide new insights into how humans adapt to changing environmental conditions. Incorporating major events into the model, like mass migrations or glacial retreats, may lead to even more insights.
影响因子：
3.4
作者：
Alonso S;Izagirre N;Smith-Zubiaga I;Gardeazabal J;Díaz-Ramón JL;Díaz-Pérez JL;Zelenika D;Boyano MD;Smit N;de la Rúa C
通讯作者：
de la Rúa C