The evolutionary and functional features of RNA editing are well studied in mammals, cephalopods, and insects, but not in birds. Here, we integrated transcriptomic and whole-genomic analyses to exhaustively characterize the expansive repertoire of adenosine-to-inosine (A-to-I) RNA editing sites (RESs) in the chicken. In addition, we investigated the evolutionary status of the chicken editome as a potential mechanism of domestication. We detected the lowest editing level in the liver of chickens, compared to muscles in humans, and found higher editing activity and specificity in the brain than in non-neural tissues, consistent with the brain's functional complexity. To a certain extent, specific editing activity may account for the specific functions of tissues. Our results also revealed that sequences critical to RES secondary structures remained conserved within avian evolution. Furthermore, the RNA editome was shaped by purifying selection during chicken domestication and most RESs may have served as a selection pool for a few functional RESs involved in chicken domestication, including evolution of nervous and immune systems. Regulation of RNA editing in chickens by adenosine deaminase acting on RNA (ADAR) enzymes may be affected by non-ADAR factors whose expression levels changed widely after ADAR knockdown. Collectively, we provide comprehensive lists of candidate RESs and non-ADAR-editing regulators in the chicken, thus contributing to our current understanding of the functions and evolution of RNA editing in animals.
目前有关RNA编辑在哺乳动物、头足类动物和昆虫等中的进化和功能研究已有了很好的进展，但在鸟类中仍存在很大空白。该研究中，通过整合转录组学和全基因组学分析，我们详细地描绘了鸡中腺嘌呤核苷转为次黄嘌呤核苷（Adenosine-to-inosine, A-to-I）的RNA编辑模式的位点（RNA editing sites, RESs）图谱。此外，我们还研究了RNA编辑在家鸡驯化过程中可能的作用机制。我们发现，鸡肝脏的编辑水平最低，这与已报道的人的肌肉编辑水平最低的结论不同。而鸡大脑的编辑活性和特异性均显著高于非神经组织，这与大脑的功能复杂性一致，因为在一定程度上，组织特异的编辑活性或许可以为其特定的功能作出解释。同时，我们的研究结果还显示，影响RESs二级结构形成的关键序列在鸟类进化过程中是保守的，并在家鸡的驯化过程中受到负选择。大多数RESs可能构成一个选择池，用以筛选出在驯化过程起功能性作用的少数RESs，譬如参与神经系统和免疫系统的进化等。最后，我们的结果也揭示，在鸡里，RNA编辑酶ADARs对RNA编辑的调控可能受到非ADAR（non-ADAR）因子的影响，这些因子的表达水平在ADAR基因被敲除后发生了显著的变化。总而言之，我们提供了鸡RESs和non-ADAR编辑调控因子的综合列表，它们或将促进我们对RNA编辑在动物功能和进化中的可能作用的理解。.
Keywords: Chicken; Domestication; Evolution; Population genomics; RNA editing; Transcriptomics.