Cosmic rays may explain life’s bias for right-handed DNA

Ultimately, the fact that researchers struggle to find a theory that balances the rise of chirality against the destruction of biological materials suggests that our ancestors may have been lucky to find that fine line. There is something special about planets like the Earth that protect this kind of chemistry.

2021-08-02: More details on this astounding achievement. They were able to sequence a 1.5 kilobase chiral DNA plus the Pasteur encoding stunt.

The chirally inverted L-DNA, possessing the same informational capacity but resistant to biodegradation, may serve as a robust, bioorthogonal information repository. Here we chemically synthesize a 90-kDa high-fidelity mirror-image Pfu DNA polymerase that enables accurate assembly of a kilobase-sized mirror-image gene. We use the polymerase to encode in L-DNA an 1860 paragraph by Louis Pasteur that first proposed a mirror-image world of biology. We realize chiral steganography by embedding a chimeric D-DNA/L-DNA key molecule in a D-DNA storage library, which conveys a false or secret message depending on the chirality of reading. Furthermore, we show that a trace amount of an L-DNA barcode preserved in water from a local pond remains amplifiable and sequenceable for 1 year, whereas a D-DNA barcode under the same conditions could not be amplified after 1 day.

2022-10-28: The same group doing the next step, a chiral RNA polymerase. This one is about 10% larger than previous work on the DNA polymerase as measured in kDA.

Zhu chemically synthesized a 100-kDA mirror-image T7 RNA polymerase, which enabled efficient and faithful transcription of high-quality l-RNAs as long as 2.9 kilobases. A massive, 883 amino acid protein, it lay well beyond the limits of traditional chemical synthesis. But an analysis of T7s x-ray crystal structure showed the enzyme could likely be split into 3 sections, each stitched from short segments. In solution, the fragments naturally folded into their proper 3D shapes and assembled themselves into a working T7.

The mirror-image RNAs fashioned by the polymerase were far more stable than the normal versions produced by a regular T7, because they were untouched by the naturally occurring RNA chewing enzymes that almost unavoidably contaminate such experiments and quickly destroy normal RNAs.

Now, Zhu needs to make the remaining components of a mirror-image ribosome. The 3 RNA fragments they synthesized make up 66% of the total mass of a ribosome. What remains are the 54 ribosomal proteins and several proteins that work in concert with the ribosome, all of which are smaller and thus likely easier to synthesize. Then the question is whether the full parts kit will assemble into a ribosome.

Even if they do, the resulting molecular machines might still not be functional. In order to churn out proteins, ribosomes must work in conjunction with a suite of additional helper proteins. To make this work inside a living cell, Church thinks it will be necessary to rewrite an organism’s genetic code so the engineered ribosome can recognize all those proteins, particularly the 20 that ferry amino acids for building new proteins.

2023-08-28: nonlinear optics to detect chirality

They have realized a technique that can completely distinguish enantiomers in solution in an all-optical manner: no chemical tags, no particular UV/VIS absorbance needed from the compound structures, etc. And it is extremely fast and extremely sensitive, as opposed to traditional methods like optical rotation, circular dichroism, etc.

2023-09-08: What about magnetism?

Magnetic surfaces on minerals in bodies of water on the primordial Earth, charged by the planet’s magnetic field, could have served as “chiral agents” that attracted some forms of molecules more than others, kicking off a process that amplified the chirality of biological molecules, from RNA precursors all the way to proteins and beyond. Their proposed mechanism would explain how a bias in the makeup of certain molecules could have cascaded outward to create a vast network of chiral chemistry supporting life.

It’s not the only plausible hypothesis, but “it’s one of the coolest because it ties geophysics to geochemistry, to prebiotic chemistry, and ultimately to biochemistry”