Researchers at UC Berkeley have found a microbe that breaks a fundamental rule of the genetic code. This archaea, a methane-producing single-celled organism, doesn't always treat a three-letter DNA sequence called TAG as a stop signal. Instead, it reads TAG as a code to add pyrrolysine, a rare 21st amino acid, and keeps building the protein. The discovery came from lab work and data analysis over recent years. It happened at UC Berkeley, with help from teams at Oak Ridge National Lab and others. Why does it matter? These microbes play a role in methane cycles, a big factor in climate change.
Key Takeaways
- UC Berkeley team identified archaea that repurpose the TAG stop codon to encode pyrrolysine in all proteins.
- This creates a new genetic code with 62 sense codons for 21 amino acids, found in multiple archaeal groups.
- The microbe uses pyrrolysine for enzymes that break down methylamines into methane.
- Findings open paths for bioengineering new proteins in bacteria like E. coli.
Background
DNA holds the instructions for life. It uses groups of three letters, called codons, to tell cells which amino acid to add when making proteins. Proteins do most of the work in cells. They build structures. They speed reactions. They fight invaders. Normally, 64 possible codons match 20 standard amino acids. Three codons—TAG, TAA, TGA—say stop. No more amino acids. Protein complete.
But life bends rules sometimes. Some bacteria and eukaryotes tweak the code. They add extra amino acids like selenocysteine or pyrrolysine. Pyrrolysine shows up in a few microbes. It helps them handle compounds with methyl groups, like methylamines. These microbes turn methylamines into methane. Methane traps heat. It's 27 times worse than CO2 over 100 years.
Archaea sit between bacteria and eukaryotes on life's tree. They thrive in hot springs. Deep seas. Your gut. Most follow the standard code. But UC Berkeley's Jill Banfield and her team dug deeper. They scanned genomes from hard-to-grow microbes. Metagenomics helped. That's studying DNA straight from environments, no lab cultures needed.
Years of work led here. Veronika Kivenson led the charge. She worked with Banfield, chemist Alanna Schepartz, and others from Institut Pasteur and CGEM. They published in Science. Their find? Multiple archaea groups read TAG as pyrrolysine every time. Not just in one protein. Genome-wide. Everywhere TAG appears.
And this ties to ancient water discoveries deep in mines, where old microbes hint at life's tough roots. Or lost moon theories for Saturn's rings, showing nature's wild paths.
Key Details
The team started with computer predictions. They spotted TAG codons in genes for methyltransferases. Those enzymes grab methylamines. Add them to coenzymes. Spit out methane. Pyrrolysine sits at the heart of these enzymes. Without it, no dice.
But predictions need proof. They turned to proteomics. Mass spectrometry at Oak Ridge National Lab checked proteins. Robert Hettich's group ran tests. They confirmed pyrrolysine in over 1,800 proteins. From various jobs. Not just methane makers.
How the Code Works
Standard code: TAG stops translation. Ribosomes quit. Protein folds up.
New code: TAG means pyrrolysine. A special tRNA grabs it. Synthetase charges the tRNA with pyrrolysine. Machinery skips the stop. Adds the amino acid. Keeps going. Result? 62 sense codons. 21 amino acids. No ambiguity in these archaea.
Banfield's team found this code popped up many times. In different archaeal branches. Not one family. Several. That challenges old ideas. Code changes seemed rare. Frozen early in evolution. But here, it evolved again and again. Driven by need for methylamine metabolism.
They tested it. Took pyrrolysine systems from eight archaea groups. Put them in E. coli bacteria. Added a TAG in a gene for green fluorescent protein. Normal E. coli? Half protein. No glow.
With the system? Full protein. Bacteria lit up green. Worked across strains. Schepartz called it a natural fix to bioengineering headaches.
"The organisms identified in this work appear to have figured out a natural solution to this problem. It's amazing, and yet another fantastic example of how biology hides secrets that drive biotechnology innovation." – Alanna Schepartz, UC Berkeley chemist
These archaea live in cow guts. Landfills. Oily reservoirs. Anywhere methylamines build up. Dead plants. Animal waste. They eat those. Burp methane. Understanding their code fixes past errors. Scientists missed pyrrolysine proteins before. Thought genes coded junk.
What This Means
Methane from microbes adds to warming. These archaea contribute. Knowing their full proteins helps track methane flows. Model emissions better. Spot weak points. Maybe block methylamine eaters. Cut gas output.
Bioengineers get tools. Pyrrolysine systems from these archaea work in E. coli. Yeast. Human cells. Add unnatural amino acids. Build proteins drugs can't match. Antibodies with new tricks. Therapies that last. Materials like tough polymers.
Peter Schultz pioneered this at UC Berkeley decades ago. Repurposed stops for odd amino acids. Now, nature hands better kits. Less trial and error. Higher yields. Schepartz's tests prove it.
Evolution lesson too. Codes aren't fixed. They shift when pressure hits. Metabolic needs win. Gain the code easy. Lose it? Harder. Pyrrolysine hides in must-have proteins.
Researchers eye more. Hunt TAG readers elsewhere. Test in complex setups. Like Neanderthal DNA mating stories, this rewrites history books.
Biotech firms watch. Custom bugs for fuels. Chemicals. Drugs. US edges ahead in the race.
Frequently Asked Questions
What is pyrrolysine?
Pyrrolysine is the 21st amino acid. Rare. Helps certain microbes process methylamines into methane. These archaea need it for key enzymes.
Why did this genetic code change happen?
The archaea faced methylamines in their world. Needed pyrrolysine enzymes to eat them. Evolved to read TAG as that amino acid code, not stop.
Can this help fight climate change?
Yes. Better grasp of these methane makers lets us track and maybe curb emissions from guts, waste sites, and soils.
Frequently Asked Questions
What makes this genetic code different?
In these archaea, the TAG codon always codes for pyrrolysine instead of stopping protein synthesis. This expands the code to 21 amino acids across the genome.
How was the discovery confirmed?
Bioinformatics predicted it, proteomics with mass spectrometry proved pyrrolysine in proteins, and tests in E. coli showed the system works.
What role do these microbes play?
They produce methane by metabolizing methylamines, contributing to greenhouse gas emissions in environments like animal guts and landfills.
