New Review out in Nature Reviews Genetics - Emergence and evolution of protein-coding de novo genes

A new review by Erich Bornberg-Bauer and Lars A. Eicholt summarizes current understanding of protein-coding de novo genes—genes that originate from previously non-coding DNA. Once considered rare or unlikely, de novo gene birth has become a rapidly growing research area, driven by expanding genome resources, improved comparative genomics, and new functional and structural assays. At the same time, key aspects remain debated: estimates of how often de novogenes arise and persist differ between studies, and their properties can challenge classical expectations about how new genes and proteins emerge.

The review discusses how de novo genes are identified (including phylogenetic and synteny-based strategies), which genomic and regulatory features facilitate their emergence, and how population-level gain–loss dynamics shape their fate. It also surveys what is known about the length, intrinsic disorder, structural properties, and cellular functions of proteins encoded by de novo genes, highlighting both experimental evidence and computational advances (including modern structure prediction and large-scale screening approaches). Finally, the article outlines open questions and future directions—aiming to help reconcile differing perspectives and to clarify when, how, and why novel coding sequences become integrated into biological systems over evolutionary time.

 

Funding

E.B.-B. acknowledges funding in pursuit of this Review from HFSP (Human Frontiers of ScienceProgramme, RGP0006/2013 and RGP004/2023); DFG (Deutsche ForschungsgemeinschaftBO-2544/20-1;503272152, BO-2544-22/1;503348080, BO-2544-12/1;298390451); VolkswagenFoundation (98181); University of Münster Topical Programme; Alexander von HumboldtFoundation (3.3-1213745-Fra-HFST-P). Some parts of this research were conducted whilevisiting the Okinawa Institute of Science and Technology (OIST) through the Theoretical Sciences Visiting Program 314 (TSVP). L.A.E. has been supported by EMBO Scientific Exchange Grant 10944.

 

Original publication

Bornberg-Bauer, E., Eicholt, L.A. Emergence and evolution of protein-coding de novo genes. Nat Rev Genet (2026). DOI: 10.1038/s41576-025-00929-9

Further Information:

Read-Only Link: https://rdcu.be/e09SM

Full Publication: https://www.nature.com/articles/s41576-025-00929-9

Bornberglab at the Institute for Evolution and Biodiversity: bornberglab.org