Friday, April 4, 2014

On the Origin of the Genes of Viruses - 4

Machines assembling parts into a complete machine
Today, we take a first glance into the evolution of the ribosome, which is a sophisticated molecular machine that makes and/or assembles other molecular machines, such as RNA and/or DNA, and the like (Wikipedia).

The ribosome has also been called a molecular factory that perhaps can be envisioned metaphorically by the photo to the left.

In this hypothetical look at the evolution of the ribosome (perhaps we should call its earliest manifestations a "robosome"), let's first remember one principle we talked about yesterday, which is that evolution in general is said to proceed from simple to complex.

So, let's boil this down and apply it to molecular machine evolution with this basic principle: all parts of a machine must actually exist before the complete machine itself can actually be made to exist (i.e. assembled).

Whether you are building a model car or a model airplane, or even real ones, you must first have all the parts before you can assemble those parts into a complete vehicle.

The factory in the photo at the top of this post could not assemble a complete entity, in this case an automobile, if any part was missing or did not yet exist.

That is the hypothetical model I am following to articulate how the "robosome" / ribosome must have incrementally evolved part by part, piece by piece, and simple to complex (some viruses still have molecular motors that help with genetic work -- see this).

Before proceeding to the parts, notice that we have a modern example of a primitive or prototypical ribosome:
... 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.

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
(Biologists Create Self-replicating RNA Molecule, cf. Wikipedia "Ribozyme"). The development of the replication dynamics in that lab went from simple to complex.

Eventually, they ended up with a working model of what is a conceptual form of a partial or primitive ribosome or ribozyme.

Another metaphor, in addition to the photo at the top of this post, might be a garage factory that evolved into the modern Apple Computer factory.

Metaphor aside, there are peer-reviewed papers which articulate the hypothesis of the dynamics of RNA abiotic evolution:
"Discoveries demonstrating that RNA can serve genetic, catalytic, structural, and regulatory roles have provided strong support for the existence of an RNA World that preceded the origin of life as we know it. Despite the appeal of this idea, it has been difficult to explain how macromolecular RNAs emerged from small molecules available on the early Earth." (The origin of the RNA world)
"It is now generally accepted that our familiar biological world was preceded by an RNA world in which ribosome-catalyzed, nucleic-acid coded protein synthesis played no part. If the RNA world was the first biological world there is little that one can learn from biochemistry about prebiotic chemistry, except that the formation and polymerization of nucleotides were once prebiotic processes. If the RNA world was not the first biological world, the above conclusion may not be justified, and one can speculate that the monomers of earlier genetic polymers might be recognizable as important biochemicals. This suggests that the construction of replicating polymers from simple, not necessarily standard, aminoacids should be explored." (Some consequences of the RNA world hypothesis).
"The general notion of an “RNA World” is that, in the early development of life on the Earth, genetic continuity was assured by the replication of RNA and genetically encoded proteins were not involved as catalysts. There is now strong evidence indicating that an RNA World did indeed exist before DNA- and protein-based life. However, arguments regarding whether life on Earth began with RNA are more tenuous. It might be imagined that all of the components of RNA were available in some prebiotic pool, and that these components assembled into replicating, evolving polynucleotides without the prior existence of any evolved macromolecules." (The Origins of the RNA World)
"This year marks the 50th anniversary of a proposal by Alex Rich that RNA, as a single biopolymer acting in two capacities, might have supported both genetics and catalysis at the origin of life. We review here both published and previously unreported experimental data that provide new perspectives on this old proposal." (The “Strong” RNA World Hypothesis: Fifty Years Old)
(see also Wikipedia, "RNA World Hypothesis"). Carbon-based living parts are the essential parts for biotic evolution to assemble into complete entities, so, until carbon-based life existed only abiotic evolution could take place.

Yes, abiotic evolution via abiotic mutation and abiotic-selection (before Darwinian "natural selection" yet existed) is to be explored further in future posts (the next post considers the cosmic abiotic robosome).

The next post in this series is here, the previous post in this series is here.

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