Biological Sciences Division
Published December 18, 2024 | Version v1
Journal article Open

The three-dimensional genome drives the evolution of asymmetric gene duplicates via enhancer capture-divergence

Creators

  • 1. University of Chicago
  • 2. Rockefeller University
  • 3. University of Vienna
  • 4. Chinese Institute for Brain Research
  • 5. Yale University
  • 6. University of California, Irvine
  • 7. Columbia University

Description

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.

Data availability

D. melanogaster Hi-C libraries form S2 cells: PRJNA393992 are publicly available. D. teissieri Hi-C libraries from adult females: SRR12331760 are publicly available. D. pseudoobscura Hi-C library from L3 larvae: PRJNA948678 is newly generated. D. pseudoobscura reference genome: PRJNA596268 is publicly available. D. melanogaster 4C-Seq data from L3 larve: PRJNA948431 are newly generated. scRNA-seq data: PRJNA995212. All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Scripts for analyses may be found at https://github.com/ulee-sciscripts/enh_cap_div_scripts and https://doi.org/10.5061/dryad.x69p8czv0.

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Additional details

Identifiers

DOI
10.1126/sciadv.adn6625
Other
oai:uchicago.tind.io:14284

Funding

National Science Foundation
MCB2020667
National Science Foundation
2410289
National Institutes of Health
GM7197-42
National Institutes of Health
1R01GM116113-01A1
National Institutes of Health
F32GM146423
National Institutes of Health
R01-GM115523
National Institutes of Health
MIRA R35GM133780

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Ecology and Evolution, Human Genetics, Pathology