Stephen Tang

Many thanks to all co-authors for their collective efforts in bringing this story to fruition! And a special thanks to Sam for continually fostering a spirit of curiosity, creativity, and rigor in all aspects of our work.

Collectively, our findings suggest that telomerase-like activity emerged in an ancient bacterial ancestor, and was co-opted in early organisms with linear genomes to set the stage for the evolution of modern eukaryotes.

Furthermore, when equipped with the template sequence from the telomerase RNA, DRT10 readily synthesized telomeric DNA repeats.

We teamed up with RT aficionado @pentamorfico.bsky.social from the Pinilla-Redondo Lab to build a new phylogenetic tree of RTs across all domains of life.

Remarkably, this revealed that the DRT enzymes are bacterial homologs of TERT.

We found that DRT10 synthesizes tandem-repeat cDNAs through a mechanism strikingly reminiscent of DNA repeat addition by telomerase. But does this similarity represent convergent evolution or shared ancestry?

Following our recent work on the DRT2 and DRT9 antiviral immune systems in bacteria (linked below), which revealed intricate mechanisms of RNA-templated repetitive DNA synthesis, we began studying a new system, DRT10.

DRT2: www.science.org/doi/10.1126/...

DRT9: www.nature.com/articles/s41...

Telomerase is found in nearly all eukaryotes and acts as a critical safeguard against genome instability from progressive DNA loss. Its aberrant activation is also key to the proliferation of cancer cells.

And yet, the evolutionary origin of telomerase has long remained unresolved.

Forty years ago, Carol Greider and Elizabeth Blackburn discovered an enzyme that solves this problem. Telomerase, which comprises a reverse transcriptase (TERT) and RNA (TR), directly extends chromosome ends by adding DNA repeats templated by the TR.

Linear chromosomes shorten with each round of cell division. Famously known as the “end-replication problem,” this phenomenon eventually leads to cellular senescence and is one of the hallmarks of aging.

Genome maintenance by telomerase is a fundamental process in nearly all eukaryotes. But where does it come from?

Today, we report the discovery of telomerase homologs in a family of antiviral reverse transcriptases, revealing an unexpected evolutionary origin in bacteria.

doi.org/10.1101/2025...

Our new paper on DRT9 is now online @nature.com! This remarkable reverse transcriptase synthesizes homopolymeric DNA to protect bacteria against viral infection. Congrats to all authors!

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

Thought polyA tails were only for mRNA? Here's a protein with a poly-dA tail, that it synthesized itself!