De novo origin of numerous microproteins in enterobacteria

Igor Fesenko, Svetlana A Shabalina, Gisela Storz, Eugene V Koonin.
Nucleic Acids Research, Volume 53, Issue 22, 11 December 2025
doi.org/10.1093/nar/...

A significant proportion of de novo smORFs overlap with regulatory elements in intergenic regions, suggesting that translation-coupled regulatory mechanisms affecting downstream gene expression may contribute to de novo gene emergence.

Our analysis indicates that bacterial pangenomes are largely closed, suggesting that the capacity of intergenic regions to generate de novo genes is limited.

Because identifying de novo gene emergence in bacterial genomes is challenging, we constructed orthologous groups of microproteins (microOGs) based on sequence similarity and conservation of gene synteny in flanking regions

De novo origin of numerous microproteins in enterobacteria Abstract. Bacterial genomes encompass numerous small open reading frames (smORFs), some of which encode functional microproteins or perform noncoding regul

I am happy to present our new paper on the de novo birth of microproteins in bacterial intergenic regions, conducted in collaboration with the Storz lab.

academic.oup.com/nar/article/...

hey bluesky 👋 visa hurdles mean I’m looking for opportunities outside the US. I’m a computational biologist (bacterial + phage genomics, postdoc in Koonin’s group @ NIH). I am interested in teaming up on funding apps. reach out if this resonates!

Excitingly, treating moss plants with sulfated PSY and PSY-like peptides stimulated cell elongation #peptides

Comparative analysis of small secreted peptide signaling during defense response: insights from vascular and non‐vascular plants Small secreted peptides (SSPs) play an important role in modulating immune responses in all land plants. However, the evolution of stress peptide signaling in different plant phyla remains poorly und...

Happy to share our manuscript is now published🎉 in @PPLplantarum

A key finding: novel stress inducible peptides in bryophytes

dx.doi.org/10.1111/ppl....

Read out latest issue here: www.cell.com/molecular-ce...

Congratulations!🎉

The role of chloroplast protein remodeling in stress responses and shaping of the plant peptidome In addition to photosynthesis, chloroplasts perform a variety of important cellular functions in the plant cell, which can, for example, regulate plant responses to abiotic and biotic stress conditio...

Probably chloroplast proteins play a role in this process

nph.onlinelibrary.wiley.com/doi/full/10....

Specific pools of endogenous peptides are present in gametophore, protonema, and protoplast cells of the moss Physcomitrella patens - BMC Plant Biology Background Protein degradation is a basic cell process that operates in general protein turnover or to produce bioactive peptides. However, very little is known about the qualitative and quantitative ...

We also showed that enhanced protein degradation leads to the generation of peptides with antimicrobial activity, functioning as a first line of defense against pathogens

bmcplantbiol.biomedcentral.com/articles/10....

Phytohormone treatment induces generation of cryptic peptides with antimicrobial activity in the Moss Physcomitrella patens - BMC Plant Biology Background Cryptic peptides (cryptides) are small bioactive molecules generated via degradation of functionally active proteins. Only a few examples of plant cryptides playing an important role in pla...

This aligns with our previous study on plants, where we proposed the concept of “active management” of peptide pools under stress conditions #peptides #antimicrobial

bmcplantbiol.biomedcentral.com/articles/10....

Cell-autonomous innate immunity by proteasome-derived defence peptides - Nature Proteasomal degradation of cellular proteins generate defence peptides constitutively and in response to bacterial infection. Such peptides might provide a source of natural antibiotics that...

A fascinating paper demonstrating that proteasome-derived peptides can serve as a natural source of antimicrobial peptides

www.nature.com/articles/s41...

What is the difference between small and weeny?

Thank you so much, Nikos! Yes, we significantly improved the manuscript with our collaborators in the wet lab

The hidden bacterial microproteome This study uncovers thousands of microprotein families encoded by intergenic small open reading frames (smORFs) in bacterial genomes and provides a publicly available resource featuring structural predictions, predicted interactions between microproteins…

Online Now: The hidden bacterial microproteome

The overexpression of species-specific microprotein which we predicted to interact with calcium transporter (Bax protein family) resulted in downregulation of protein level in cell

Google Colab

Complete information on the predicted microproteins is available here colab.research.google.com/github/IgorF...

Compared to the preprint, our esteemed collaborators validated selected microproteins by western blotting

The hidden bacterial microproteome This study uncovers thousands of microprotein families encoded by intergenic small open reading frames (smORFs) in bacterial genomes and provides a publicly available resource featuring structural pre...

Excited to share our publication on bacterial microproteome www.cell.com/molecular-ce...
#microproteins

Hi everyone! We are still welcoming applicants for a computational postdoc position. If your profile fits our lab interests, please do reach out to me for more information or apply directly via the link below. I'm looking forward to reading your application! www.academictransfer.com/en/jobs/3488...

We’re looking for a postdoc in plant bioengineering to join an exciting interdisciplinary ERC project @UPSC! Work in a vibrant, international environment alongside top researchers, pushing the boundaries of plant science. Apply here: shorturl.at/smdwD

Simulating 500 million years of evolution with a language model More than three billion years of evolution have produced an image of biology encoded into the space of natural proteins. Here we show that language models trained at scale on evolutionary data can gen...

Very cool paper in Science:
Simulating 500 million years of evolution with a language model
www.science.org/doi/10.1126/...

The astonishing scientists who starved to protect plants during the Second World War The trials and tribulations of the world’s first seed bank reveal botanists’ enormous generosity and sacrifice during the siege of Leningrad.

Book review: The astonishing scientists who starved to protect plants during the Second World War

https://go.nature.com/4gSJOfk

### Job alert, please repost! ###

We're recruiting a computational postdoc in evolutionary genetics to help us understand whether recently emerged ncORFs and microproteins play roles in childhood brain cancers. Will you become part of our team? werkenbijprinsesmaximacentrum.nl/en/vacancy/p...

Happy New Year!☃️

‘Dark proteome’ survey reveals thousands of new human genes Database confirms that overlooked segments of the genome code for a multitude of tiny proteins

Do you want to go further with your proteomics? Looking for something new in cancer?

Check out microproteins!

Thanks to @science.org for featuring this work, in collaboration with @sebastiaanvheesch.bsky.social, #HUPO, @gencodegenes.bsky.social

www.science.org/content/arti...

🔎 microprotein
🧬 💻

Small proteins, mighty potential! Whether you're an afficionado or just interested in diving into the world of #microproteins, join us for a Keystone meeting February 2025 in Beverly MA: www.keystonesymposia.org/conferences/...