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Emx2 underlies the development and evolution of marsupial gliding membranes

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posted on 2024-06-07, 06:11 authored by Jorge A Moreno, Olga Dudchenko, Charles FeiginCharles Feigin, Sarah A Mereby, Zhuoxin Chen, Raul Ramos, Axel A Almet, Harsha Sen, Benjamin J Brack, Matthew R Johnson, Sha Li, Wei Wang, Jenna M Gaska, Alexander Ploss, David Weisz, Arina D Omer, Weijie Yao, Zane Colaric, Parwinder Kaur, Judy St Leger, Qing Nie, Alexandria Mena, Joseph P Flanagan, Greta Keller, Thomas Sanger, Bruce Ostrow, Maksim V Plikus, Evgeny Z Kvon, Erez Lieberman Aiden, Ricardo Mallarino
Phenotypic variation among species is a product of evolutionary changes to developmental programs1,2. However, how these changes generate novel morphological traits remains largely unclear. Here we studied the genomic and developmental basis of the mammalian gliding membrane, or patagium—an adaptative trait that has repeatedly evolved in different lineages, including in closely related marsupial species. Through comparative genomic analysis of 15 marsupial genomes, both from gliding and non-gliding species, we find that the Emx2 locus experienced lineage-specific patterns of accelerated cis-regulatory evolution in gliding species. By combining epigenomics, transcriptomics and in-pouch marsupial transgenics, we show that Emx2 is a critical upstream regulator of patagium development. Moreover, we identify different cis-regulatory elements that may be responsible for driving increased Emx2 expression levels in gliding species. Lastly, using mouse functional experiments, we find evidence that Emx2 expression patterns in gliders may have been modified from a pre-existing program found in all mammals. Together, our results suggest that patagia repeatedly originated through a process of convergent genomic evolution, whereby regulation of Emx2 was altered by distinct cis-regulatory elements in independently evolved species. Thus, different regulatory elements targeting the same key developmental gene may constitute an effective strategy by which natural selection has harnessed regulatory evolution in marsupial genomes to generate phenotypic novelty.

Funding

This project was supported by an NIH grant to R.M. (R35GM133758). R.M. is partially supported by the Searle Scholars Program, the Sloan Foundation and the Vallee Scholars Program. E.L.A. was supported by grants from the Welch Foundation (Q-1866), an NIH Encyclopedia of DNA Elements Mapping Center Award (UM1HG009375), a US–Israel Binational Science Foundation Award (2019276), the Behavioral Plasticity Research Institute (NSF DBI-2021795), NSF Physics Frontiers Center Award (NSF PHY-2210291) and an NIH CEGS (RM1HG011016-01A1). J.A.M. was supported by an NSF fellowship (DGE-2039656). C.Y.F. was supported by an NIH fellowship (F32 GM139240-01). H.S. and B.J.B. were partially supported by an NIH training grant (T32GM007388). M.V.P. and Q.N. are supported by NIH grant R01-AR079150. M.V.P. is also supported by LEO Foundation grants LF-AW-RAM-19-400008 and LF-OC-20-000611, and W.M. Keck Foundation grant WMKF-5634988.

History

Publication Date

2024-05-02

Journal

Nature

Volume

629

Pagination

127 - 135

Publisher

Springer Nature

ISSN

0028-0836

Rights Statement

© The Author(s) 2024 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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