🧬 Life Uses 4 DNA Letters. Scientists Just Made 8 Work.

Every known organism on Earth writes its genetic instructions using the same four DNA letters: A, T, C and G.

Scientists have now shown that one of biology’s most fundamental molecular machines can read an alphabet containing eight.

Researchers tested E. coli RNA polymerase — the enzyme that reads DNA and turns its information into RNA — with synthetic DNA containing four additional chemical letters known as P, Z, B and S. Remarkably, the enzyme successfully recognized and transcribed the artificial base pairs using much of the same molecular machinery it employs for natural DNA.

Using cryo-electron microscopy at resolutions down to about 2.4 ångströms, the team could watch how the synthetic letters fit inside the polymerase. The artificial pairs adopted almost the same geometry as ordinary Watson–Crick DNA pairs, allowing the enzyme’s catalytic machinery to close around them and continue transcription. Researchers also engineered a modified version of one synthetic letter to reduce copying errors.

The implications are potentially enormous. A larger genetic alphabet could eventually produce RNA molecules with chemical capabilities unavailable to natural biology and might help scientists design new diagnostics, drugs and engineered biological systems. Expanded genetic alphabets have already been used experimentally to create molecules that recognize cancer cells.

But there is an important boundary: scientists have not created an eight-letter living organism here. The experiment demonstrates transcription by bacterial RNA polymerase; reliably replicating a full eight-letter genome and translating that expanded information into proteins inside living cells remain much harder problems.

For four billion years, life on Earth has been writing with four letters.

Apparently, biology’s machinery can read a bigger alphabet than evolution ever gave it.

#Genetics #DNA #SyntheticBiology #Biotechnology #RNA #Science

Primary paper — Nature Communications⁠