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bioRxiv · 10.1101/2022.11.30.518413

The Role of the 3-Dimensional Genome in New Gene Evolution

Lee, U.·Arsala, D.·Xia, S.·Ali, M.·Sobreira, D.·Eres, I.·Zhou, Q.·Long, M.
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Abstract

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/Umbreas future insertion site using single-cell transcriptomics, illustrating how enhancer capture provides a highly evolvable, one-step solution to Ohnos 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.

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Lee, U., Arsala, D., Xia, S., Ali, M., Sobreira, D., Eres, I., Zhou, Q., Long, M.. 2022-12-01. The Role of the 3-Dimensional Genome in New Gene Evolution. https://doi.org/10.1101/2022.11.30.518413

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