Centre for Organismal Studies, University of Heidelberg, Heidelberg, Germany.
PLoS Biol. 2011 Nov;9(11):e1001188. doi: 10.1371/journal.pbio.1001188. Epub 2011 Nov 1.
Evolutionary innovation relies partially on changes in gene regulation. While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated. Here we show evidence for the de novo genesis of enhancers in vertebrates. For this, we took advantage of the massive gene loss following the last whole genome duplication in teleosts to systematically identify regions that have lost their coding capacity but retain sequence conservation with mammals. We found that these regions show enhancer activity while the orthologous coding regions have no regulatory activity. These results demonstrate that these enhancers have been de novo generated in fish. By revealing that minor changes in non-regulatory sequences are sufficient to generate new enhancers, our study highlights an important playground for creating new regulatory variability and evolutionary innovation.
进化创新部分依赖于基因调控的变化。虽然越来越多的证据表明，这种创新是通过移动遗传元件的功能变化或调节元件的易位产生的，但据我们所知，以前从未证明过非调节/非移动序列从头产生增强子。在这里，我们展示了脊椎动物中增强子从头生成的证据。为此，我们利用硬骨鱼类最后一次全基因组复制后的大量基因丢失，系统地鉴定了那些失去编码能力但与哺乳动物保持序列保守的区域。我们发现，这些区域具有增强子活性，而同源编码区域没有调节活性。这些结果表明，这些增强子是在鱼类中从头生成的。通过揭示非调节序列的微小变化足以产生新的增强子，我们的研究强调了一个重要的场所，可以产生新的调节变异性和进化创新。
