Villar Diego, Berthelot Camille, Aldridge Sarah, Rayner Tim F, Lukk Margus, Pignatelli Miguel, Park Thomas J, Deaville Robert, Erichsen Jonathan T, Jasinska Anna J, Turner James M A, Bertelsen Mads F, Murchison Elizabeth P, Flicek Paul, Odom Duncan T
University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
Cell. 2015 Jan 29;160(3):554-66. doi: 10.1016/j.cell.2015.01.006.
The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammalian regulatory evolution.
哺乳动物的辐射与基因组非编码区的快速变化相对应,但我们对哺乳动物的调控进化缺乏全面的了解。在这里,我们通过分析H3K27乙酰化和H3K4三甲基化的基因组富集情况,追踪了来自六个不同目20种哺乳动物肝脏中活跃的启动子和增强子的进化。我们报告说,增强子的快速进化是哺乳动物基因组的一个普遍特征。大多数最近进化的增强子来自祖先DNA的适应性利用,而不是重复元件的谱系特异性扩增。相比之下,几乎所有肝脏启动子在这些物种中都是部分或完全保守的。我们的数据进一步表明,最近进化的增强子可能与正选择下的基因相关,证明了这种方法在注释基因组序列中调控适应性方面的作用。这些结果为支撑哺乳动物调控进化的功能遗传学提供了重要见解。