“Was It the Origin of Life”? Biologists Create Self-replicating RNA Molecule

CaliforniaNebula It's paradoxical that as our leading microbiologists look to create the building blocks of life in Earth-bound labs, our Universe is alive with the building blocks for DNA and RNA. The giant gas nebula in outer space are rife with sugars that form ribose –the backbone of RNA. There's no rational reason why the system of DNA and RNA that shaped life on Earth should be lmlited to our remote biosphere.

One theory of the origin of life suggests that RNA coding is what gave the primitive cellular structure of early Earth the catalyst they needed to become life. With a Universe chock full of sugar there's no reason that early RNA worlds have not been evolving in their own unique ways in many of the 100 billion galaxies estimated to exist in the observable Universe.

Meanwhile, back on Earth at the MRC Laboratory of Molecular Biology in Cambridge, UK,  have created synthetic molecules that copy genetic material. The enzyme, tC19Z, that has been synthesised could be an artificial version of one of the first enzymes that ever existed on our planet three billion years ago — and a clue to how life itself got started. Their goal is to create fully self-replicating RNA molecules in the lab.

The dominant theory of how life started involves the emergence in Earth's early history of a self-replicator — the original molecule of life was an RNA that could make copies of other RNAs, including itself.

As evolution advanced, this self-replicating molecule ceased to exist, with the majority of Earth's organisms using DNA to store their genetic information while using other enzymes to copy itself.

Led by Philipp Holliger, the Cambridge-based reseach team have tested a theory called the "RNA World Hypothesis", which suggests that life was originally based not on DNA but on a related chemical called RNA, which can carry genetic information and  fold-up into three-dimensional shapes and function as an enzyme, the biological catalyst that speeds up certain chemical reactions.

RTEmagicC_Full_length_hammerhead_ribozyme.png Holliger’s group started with an RNA enzyme called R18, which could make copies of other short pieces of RNA, although in an error-prone manner. "It’s like a keyboard with which you can only write one or two words," says Holliger.

To evolve this initial R18 RNA, the group created 50 million clones, each containing random genetic changes in the RNA sequence, and selected those with the best RNA-copying abilities. And by repeating this process a number of times, they generated progressively more powerful enzymes.

"We took all the beneficial mutations that had accumulated from various selection experiments, sorted out what’s helpful and what’s not, and combined them into a single molecule," explains Holliger.

The RNA enzyme tC19Z, created by Philipp Holliger and colleagues, functions like a self-replicator. Until now, the only known RNA-copying RNA was a molecule called R18, which can only copy RNA segments up to 14 "letters" long, and only works on certain sequences.

Holliger made a vast library of thousands of different versions of the R18 molecule and screened them to see which ones made more copies. After several cycles of copying variants and looking for new improvements, he found several, which he baked into his final synthetic enzyme, tC19Z.

tC19Z can reliably copy RNA sequences up to 95 letters long, a sevenfold increase on R18. Its performance varies depending on the sequence it's copying, but it is much less picky than R18. Holliger compares R18 to a sports car that works only on a smooth, flat road. "We have fitted a four-wheel drive, so it can go off-road a bit," he told newscientist.com.

Crucially, tC19Z can copy pieces of RNA that are almost half as long (48 per cent) as itself. If an RNA enzyme is to copy itself, it has to be able to copy sequences as long as itself, and tC19Z is closing in on that goal.

In a neat twist, Holliger's team also showed that tC19Z can make copies of another RNA enzyme, which then worked correctly. That suggests that, once the first self-replicating RNA had appeared, it would have been able to surround itself with additional molecular equipment, kick-starting the evolution of more complex life.

The Daily Galaxy via newscientist.com and  thenakedscientists.com

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Image top of page: The beautiful California Nebula in Perseus 65 light-years long, is just a small part of a giant molecular cloud that's as big as the largest such cloud in Orion. The recently found cloud is 1,470 light-years from Earth — only slightly farther than the Orion A Molecular Cloud, home of the Orion Nebula, around 1,350 light-years from us. NASA/Hubble.

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