Lee, U., Arsala, D., Xia, S., Li, C., Ali, M., Svetec, N., Langer, C.B., Sobreira, D.R., Eres, I., Sosa, D., Chen, J., Zhang, L., Reilly, P., Guzzetta, A., Emerson, J.J., Andolfatto, P., Zhou, Q., Zhao, L., Long, M. (2024). The three-dimensional genome drives the evolution of asymmetric gene duplicates via enhancer capture-divergence.  Sci. Adv. 10(51): eadn6625.

FBrf0261249

Research paper

Previous evolutionary models of duplicate gene evolution have overlooked the pivotal role of genome architecture. Here, we show that proximity-based regulatory recruitment by distally duplicated genes is an efficient mechanism for modulating tissue-specific production of preexisting proteins. By leveraging genomic asymmetries, we performed a coexpression analysis on Drosophila melanogaster tissue data to show the generality of enhancer capture-divergence (ECD) as a significant evolutionary driver of asymmetric, distally duplicated genes. We use the recently evolved gene HP6/Umbrea as an example of the ECD process. By assaying genome-wide chromosomal conformations in multiple Drosophila species, we show that HP6/Umbrea was inserted near a preexisting, long-distance three-dimensional genomic interaction. We then use this data to identify a newly found enhancer (FLEE1), buried within the coding region of the highly conserved, essential gene MFS18, that likely neofunctionalized HP6/Umbrea. Last, we demonstrate ancestral transcriptional coregulation of HP6/Umbrea's future insertion site, illustrating how enhancer capture provides a highly evolvable, one-step solution to Ohno's dilemma.

PMC11654672 (PMC) (EuropePMC)