Adaptive evolution of conserved noncoding elements in mammals.
Adaptive evolution of conserved noncoding elements in mammals.
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DOI：
10.1371/journal.pgen.0030147
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发表时间：
2007-09
期刊：
影响因子：
4.5
通讯作者：
Pritchard, Jonathan K.
中科院分区：
文献类型：
--
作者：
Kim, Su Yeon;Pritchard, Jonathan K.
保守非编码元件（CNCs）是脊椎动物基因组中一个丰富的特征。一些cnc已被证明作为顺式调控模块，但大多数cnc的功能尚不清楚。为了研究cnc的进化，我们开发了一种称为“共享率测试”的统计方法，以识别在系统发育树的分支中显示出显著替代率差异的cnc。我们报告了将该方法应用于人类、黑猩猩、狗、小鼠和大鼠基因组的98,910个CNCs比对。我们发现~ 68%的CNC根据零模型进化，其中对于每个CNC，单个参数模型在连接这五个物种的整个系统发育过程中起作用的约束水平。其余约32%的CNCs显示偏离基本模型，包括在特定分支上的加速和减速，以及偶尔在不同分支上的多次速率变化。我们发现，在一个特定的分支上，一个重要的cnc子集的进化速度明显快于局部中性速率，这为这些cnc的适应性进化提供了有力的证据。这些信号在系统发育中的分布表明，cnc的适应性进化发生在偶尔的短爆发进化中。我们的分析为未来的适应性功能研究提供了大量有希望的目标。DNA序列在进化史上的保守性是识别具有重要生物学功能区域的高度信息信号。特别是，保守的非编码区已被证明是包含在基因调控中起作用的调控元件的良好候选者。最近的研究发现，脊椎动物基因组中有数千个保守的非编码元件（CNCs），并提出了其中一些元件的可能功能，但大多数CNCs的功能仍不清楚。为了研究cnc的进化，我们开发了一种统计方法来识别在哺乳动物系统发育树的特定分支上显示进化速率变化的cnc。这些速率变化可能表明CNC功能的变化。我们将我们的方法应用于五种哺乳动物基因组的cnc，发现许多cnc在其进化过程中确实经历了速率变化。我们还发现，CNCs的一个子集显示出进化速度的加速，实际上超过了中性速率，这表明适应性进化塑造了这些元素的进化。
Conserved noncoding elements (CNCs) are an abundant feature of vertebrate genomes. Some CNCs have been shown to act as cis-regulatory modules, but the function of most CNCs remains unclear. To study the evolution of CNCs, we have developed a statistical method called the “shared rates test” to identify CNCs that show significant variation in substitution rates across branches of a phylogenetic tree. We report an application of this method to alignments of 98,910 CNCs from the human, chimpanzee, dog, mouse, and rat genomes. We find that ∼68% of CNCs evolve according to a null model where, for each CNC, a single parameter models the level of constraint acting throughout the phylogeny linking these five species. The remaining ∼32% of CNCs show departures from the basic model including speed-ups and slow-downs on particular branches and occasionally multiple rate changes on different branches. We find that a subset of the significant CNCs have evolved significantly faster than the local neutral rate on a particular branch, providing strong evidence for adaptive evolution in these CNCs. The distribution of these signals on the phylogeny suggests that adaptive evolution of CNCs occurs in occasional short bursts of evolution. Our analyses suggest a large set of promising targets for future functional studies of adaptation. Conservation of DNA sequences across evolutionary history is a highly informative signal for identifying regions with important biological functions. In particular, conserved noncoding regions have been shown to be good candidates for containing regulatory elements that have roles in gene regulation. Recent studies have found that there are many thousands of conserved noncoding elements (CNCs) in vertebrate genomes and have suggested possible functions for some of these elements, but the function of most CNCs remains unknown. To study the evolution of CNCs, we developed a statistical method to identify CNCs that show changes in evolutionary rates on particular branches of the mammalian phylogenetic tree. Those rate changes may indicate changes in the function of a CNC. We applied our method to CNCs of five mammalian genomes, and found that, indeed, many CNCs have experienced rate changes during their evolution. We also found a subset of CNCs showing accelerations in evolutionary rate that actually exceed the neutral rates, suggesting that adaptive evolution has shaped the evolution of those elements.
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