Kavli Affiliate: Li Zhao
| Authors: UnJin Lee, Deanna Arsala, Shengqian Xia, Cong Li, Mujahid Ali, Nicolas Svetec, Christopher Langer, Debora Sobreira, Ittai Eres, Dylan Sosa, Jianhai Chen, Li Zhang, Patrick Reilly, Alexander Guzzetta, J.J. Emerson, Peter Andolfatto, Li Zhao and Manyuan Long
| Summary:
Previous evolutionary models of duplicate gene evolution have overlooked the pivotal role of genome architecture. Here, we show that proximity-based regulatory recruitment of distally duplicated genes (enhancer capture) is an efficient mechanism for modulating tissue-specific production of pre-existing proteins. By leveraging genomic asymmetries in synteny and function that distinguish new genes evolving under enhancer capture-divergence (ECD) from those evolving under previous models, we performed a co-expression analysis on Drosophila melanogaster tissue data to show the generality of ECD as a significant evolutionary driver of asymmetric, distally duplicated genes. We use the recently evolved gene HP6/Umbrea, which duplicated <15 million years ago (mya), as an example of the ECD process. By assaying genome-wide chromosomal conformations in multiple Drosophila species, we show that HP6/Umbrea was inserted into a pre-existing, evolutionarily stable 3D genomic structure spanning over 125kb. We then utilize this data to identify a newly discovered enhancer (FLEE1), buried within the coding region of the highly conserved, essential gene MFS18, that likely neo-functionalized HP6/Umbrea, thereby driving the new duplicate gene copy to fixation. Finally, we demonstrate ancestral transcriptional co-regulation of HP6/Umbrea's future insertion site using single-cell transcriptomics, illustrating how enhancer capture provides a highly evolvable, one-step solution to Ohno's Dilemma. The intuitive molecular mechanism underpinning the ECD model unveils a novel and robust framework to understand the fixation and neofunctionalization of distally duplicated genes.