Pervasive adaptive protein evolution apparent in diversity patterns around amino acid substitutions in Drosophila simulans.
Pervasive adaptive protein evolution apparent in diversity patterns around amino acid substitutions in Drosophila simulans.
复制标题
模拟果蝇中氨基酸取代的多样性模式中普遍存在适应性蛋白质进化。
DOI：
10.1371/journal.pgen.1001302
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发表时间：
2011-02-10
期刊：
影响因子：
4.5
通讯作者：
Sella G
中科院分区：
文献类型：
--
作者：
Sattath S;Elyashiv E;Kolodny O;Rinott Y;Sella G
在果蝇中，多条证据表明基因组的有益替换可能是常见的。然而，所有这些都受到混杂因素的影响，因此对证据的解释-特别是关于有益替代品的比率和强度的结论-仍然是试探性的。在这里，我们使用D. simulans和其近亲的测序基因组，以构建一个容易解释的表征积极选择的影响：围绕氨基酸取代的平均中性多样性的形状。正如在经常性的选择性扫描下所预期的那样，我们发现氨基酸周围的多样性水平有一个低谷，但同义取代周围没有，这是一种在替代模型下预期不到的独特模式。这种表征比以前的方法更丰富，以前的方法依赖于有限的数据摘要（例如，散点图的斜率），并以直接的方式与潜在的选择参数相关，使我们能够对适应的普遍性和强度做出更可靠的推断。具体来说，我们开发了一个基于聚结的模型的形状的整个曲线，并使用它来推断自适应参数的最大似然。我们的推断表明，约13%的氨基酸取代引起选择性扫描。有趣的是，它揭示了两类有益的固定：少数（约3%）似乎有很大的选择性影响，并占多样性减少的大部分，其余10%，似乎有非常弱的选择性影响。因此，这些估计有助于调和先前发表的选择强度估计之间的明显冲突。更一般地说，我们的研究结果为果蝇中强有益的替代提供了明确的证据，并说明了如何利用快速积累的全基因组数据来解决有关适应遗传基础的持久问题。描述基因组有益变化的性质对我们理解适应至关重要。为了做到这一点，研究人员确定并分析了有益的变化在物种内和物种之间的遗传变异模式中留下的足迹。为了教我们适应性进化，这些足迹需要是特定的积极选择，以及足够丰富，以允许可靠的推论。在这里，我们确定了这样一个足迹：一个明显的低谷，在平均水平的遗传多样性周围的氨基酸取代整个D。simulans genome.基于这种模式，我们推断大约13%的氨基酸取代是有益的，其中少数（3%）赋予近0.5%的大选择性优势，而其中大多数（10%）赋予约0.01%的小得多的优势。这些发现提供了深入了解选择效应的分布，这些选择效应推动了D。simulans的基因组，并建议如何广泛不同的估计，在以前的研究中获得的果蝇可能会协调。此外，我们介绍的方法很容易适用于其他类群，因此应该有助于获得重要的见解，适应性进化的速度和强度如何根据生活史，种群规模和生态而变化。
In Drosophila, multiple lines of evidence converge in suggesting that beneficial substitutions to the genome may be common. All suffer from confounding factors, however, such that the interpretation of the evidence—in particular, conclusions about the rate and strength of beneficial substitutions—remains tentative. Here, we use genome-wide polymorphism data in D. simulans and sequenced genomes of its close relatives to construct a readily interpretable characterization of the effects of positive selection: the shape of average neutral diversity around amino acid substitutions. As expected under recurrent selective sweeps, we find a trough in diversity levels around amino acid but not around synonymous substitutions, a distinctive pattern that is not expected under alternative models. This characterization is richer than previous approaches, which relied on limited summaries of the data (e.g., the slope of a scatter plot), and relates to underlying selection parameters in a straightforward way, allowing us to make more reliable inferences about the prevalence and strength of adaptation. Specifically, we develop a coalescent-based model for the shape of the entire curve and use it to infer adaptive parameters by maximum likelihood. Our inference suggests that ∼13% of amino acid substitutions cause selective sweeps. Interestingly, it reveals two classes of beneficial fixations: a minority (approximately 3%) that appears to have had large selective effects and accounts for most of the reduction in diversity, and the remaining 10%, which seem to have had very weak selective effects. These estimates therefore help to reconcile the apparent conflict among previously published estimates of the strength of selection. More generally, our findings provide unequivocal evidence for strongly beneficial substitutions in Drosophila and illustrate how the rapidly accumulating genome-wide data can be leveraged to address enduring questions about the genetic basis of adaptation. Characterizing the nature of beneficial changes to the genome is essential to our understanding of adaptation. To do so, researchers identify and analyze footprints that beneficial changes leave in patterns of genetic variation within and between species. In order to teach us about adaptive evolution, these footprints need to be specific to positive selection as well as rich enough to allow for reliable inferences. Here, we identify such a footprint: a pronounced trough in the average levels of genetic diversity surrounding amino acid substitutions throughout the D. simulans genome. Based on this pattern, we infer that approximately 13% of amino acid substitutions were beneficial, a minority of which (3%) conferred a large selective advantage of nearly 0.5% and the majority of which (10%) conferred a much smaller advantage of about 0.01%. These findings offer insights into the distribution of selection effects driving beneficial changes to the D. simulans genome and suggest how the widely varying estimates obtained in previous studies of Drosophila may be reconciled. Moreover, the approach that we introduce is readily applicable to other taxa and thus should help to gain important insights into how the rate and strength of adaptive evolution vary depending on life-history, population size, and ecology.
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