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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

💻 github.com/baymlab/deletion-born-fusion-manuscript 🔧 github.com/aryakaul/prefixsuffix-kmer Many thanks to co-authors @fernpizza.bsky.social , @brinda.eu & @baym.lol + GenScale/Baym lab! Funded by NIH, Packard, Pew, Sloan & a Chateaubriand Fellowship!

github.com

GitHub - baymlab/deletion-born-fusion-manuscript

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

Some ~caveats~ 🔹 We haven't proven any deletion was beneficial 🔹 No functional deletion-born fusion yet - selection analyses show mainly diversifying selection 🔹 Our method misses fusions with terminal mutations (requires exact 54bp matches)

Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

The "deletional bias" in bacterial genomes has long been framed as destructive - the pruning away of genetic material. Our findings suggest it might also be creative: deletions don't just remove genes, they can also build new ones!

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

The prefix-suffix approach isn't just for fusions. We also found: 🔹 Internal deletions 🔹 Repeat prophage insertions 🔹 Variable gene cargo in mobile elements It's a general tool for surveying structural variation at scale!

Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

But here's the CATCH: detection depends on sampling depth. When we queried well-sampled protein families we found significantly more fusions than from uniformly sampled families. We're only seeing the tip of the iceberg. As databases grow, we expect to find more.

Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

Applying the prefix-suffix approach to type strains from 5 commonly studied bacteria (E. coli, N. gonorr., M. tubercul., Strep. pneumo., C. jejuni) we find deletion-born fusions across the bacterial Tree of Life:

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

How common is this across the bacterial tree of life? We developed a new method to query 2.4M+ genomes (thanks to @zaminiqbal.bsky.social AllTheBacteria!): look for the “prefix” and “suffix” k-mer of an input gene at variable distances. If the distance changes → structural variation.

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

It's not just in the lab. During the M. tuberculosis–M. bovis split, we found 2 deletion-born fusions: 🔹 acrR-glcD 🔹 mlaE-htpX These arose during speciation and persist in natural populations today.

Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

We found one in the @relenski.bsky.social LTEE: a 57.5 kb deletion in E. coli in the Ara+1 lineage fused yjcO (unknown function) to lysU (lysyl-tRNA synthetase). Sequencing shows it's transcribed, translated, and swept to fixation in ~500 generations.

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

Most new genes die before they do anything useful, lost to genome streamlining and drift. But deletion-born fusions are different! They hitchhike on beneficial deletions, getting a "free ride" to high frequency. This buys them TIME to evolve function.

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

Here's the idea: when a deletion is beneficial (reducing genome size, removing costly genes), it can bring two distant gene fragments together. The result? A brand new fusion gene - created entirely by accident

Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

Duplication is constrained by existing templates. Overprinting produces disordered proteins & must preserve the original gene. HGT just imports genes born elsewhere. What if deletions - usually viewed as destructive - could also create?

Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

Pangenome studies find tens of thousands of protein families per species. Metagenomics reveals millions of genes of unknown function. So where does all this novelty come from?

Everyone's least favorite lab mate @kepatitis-c.bsky.social · 06/01/2026

🎉 New year, NEW PREPRINT! Bacteria exhibit astonishing genetic diversity, but where do new genes come from? My best friend Arya Kaul (/labmate in the @baym lab) investigates how advantageous deletions can spawn new genes - "deletion-born fusions." 🧵:

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Reposted by Everyone's least favorite lab mate

Shai Zilberzwige Tal @shaizil.bsky.social · 09/12/2025

Happy to share that I’m opening my lab at the Weizmann Institute of Science! We’ll study systems-level regulation of bacterial defense, driven by RNA-protein interactions shaping cell fate. Now recruiting PhD students & postdocs tinyurl.com/4yfa55vd Please reach out and share!

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 21/11/2025

“It is a damn poor mind that can think of only one way to spell a word” -Andrew Jackson

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 20/11/2025

Thanks to @baym.lol for giving me a home and the opportunity, @fernpizza.bsky.social who taught me the ropes of evolutionary biology, @wheezenfeld.bsky.social @theshreyaspai.bsky.social @nquinoneso.bsky.social, @celiasouque.bsky.social for the help along the way and the rest of the Baym lab crew!

Everyone's least favorite lab mate @kepatitis-c.bsky.social · 20/11/2025

This work highlights how interactions between MGEs can produce unique effects where both benefit from their nested existence. Furthermore, we have extended TnpB’s mechanism that sheds light on why TnpB is so successful.

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 20/11/2025

So we did a similar experiment with conjugative plasmids and found that IS605 provides offensive and defensive benefits to conjugative plasmids, acting like a primitive anti-self defense mechanism to spread plasmids between cells.

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 20/11/2025

Moreover we also noticed that IS605 tended to cluster in conserved plasmid regions of conjugative plasmids.

Everyone's least favorite lab mate @kepatitis-c.bsky.social · 20/11/2025

And specifically it is the RNA-guided nuclease activity that is responsible for this benefit - confirming our hypothesis!

Everyone's least favorite lab mate @kepatitis-c.bsky.social · 20/11/2025

Which we were able to show experimentally by competing plasmids in a displacement assay. We see plasmids that contain an IS605 have an enormous advantage over those that don’t, despite the IS itself being detrimental to plasmid replication

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 20/11/2025

But in the context of plasmids this results in a newly inserted IS605 to reprogram TnpB to target, and destroy, all IS- plasmids within the cell. With no competition only IS+ plasmids will replicate, biasing their inheritance.

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 20/11/2025

So what is going on? TnpB happens to be the ancestor to Cas12 and is also an RNA-guided nuclease. The @sternberglab.bsky.social lab figured out TnpB uses this activity to promote genomic retention by cutting excision scars - preventing IS loss.

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 20/11/2025

But not all IS families followed this trend. The IS605 family deviates while its close cousin IS200 does not. This suggests that IS605 has a unique interaction with plasmids, with the additional gene carried by IS605, TnpB, likely being responsible.

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 20/11/2025

Well they can just have more shots on goal. We found a consistent relationship between the chromosomal copy number of an IS co-occurrence on plasmids. The more you try the more you are likely to succeed (poetic I know).

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 20/11/2025

Insertion Sequences (IS) are enriched in plasmids. Which is quite curious as plasmids often have multiple copies preventing efficient inheritance of IS+ plasmids. So how do ISs come to be on plasmids in the first place?

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 20/11/2025

What is the best strategy to win any contest? Eliminate your opponents of course. Recently, my friend @fernpizza.bsky.social showed how plasmids compete intracellularly (check out his paper published in Science today!). With @baym.lol, we now know they can fight. www.biorxiv.org/content/10.1...

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 03/09/2025

There are no “O” amino acids you ding dongs

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Everyone's least favorite lab mate @kepatitis-c.bsky.social · 02/09/2025

The project has excellent lore. From contamination to a integrated tool to classify mobility, A-Dog (Arya to civilians) has found AMR gene have been increasing on MGEs likely due to the use of antibiotics. Some great graphs in here!