Original Source

If you have been reading my blog regularly, I am sure you are aware that I spend much of my time writing lessons on scientific topics. Today I would like to take a break (just for today!) from background material and basic lessons and discuss with you all a relatively new publication (If you consider released on September 21, 2016 to be new at least!). I would like to talk about this with all of you because it deals with something I brought up in another of my posts, the RNA world hypothesis. This new research article is titled RNA–DNA Chimeras in the Context of an RNA World Transition to an RNA/DNA World

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Remind Me Again @justtryme90… What’s the RNA World Hypothesis?

Well I am glad you asked! The RNA world hypothesis was the idea that all life on earth began as self-replicating RNA (RNA stands for RiboNucleic Acid). This hypothesis was another proposed by Dr. Carl Woese, a brilliant scientist who did a lot of work studying RNA’s that could catalyze chemical reactions. Woese thought that since it is possible for RNA to do all of the functions necessary for its own replication by itself (it can store information, and can catalyze reactions) that “life” began with “organisms” that were purely RNA molecules. This original world where RNA was king was called the RNA world in Woese’s hypothesis. Soon these simple ribonucleic acid “organisms” began to get too large (and too complex) and additional solutions were needed to facilitate their existence. (Citation)

Well, What Would Come Next (a slight digression to think about evolution of early “life”)

The RNA’s are getting a bit too complex and need to do something about it right? To help with their catalytic functions (their ability to make chemistry happen) proteins were evolved to lighten that chemistry load. RNA isn’t the most stable (due to it being single stranded and all of its wild self-pairing and folds), a more stable information storage molecule was needed, so slightly different nucleic acid (Deoxyribo Nucleic Acid) was evolved to do the information storing function ( only this time it was double stranded, for added stability). Another huge problem was that there were a lot of molecules that could damage the RNAs DNAs and Proteins. The easiest solution to this was for these macromolecules to isolate themselves from surrounding liquids. We all know how fats and oils repel water right? Well this is the same way that cell walls work, they use phospholipids:

These have a charged phosphate head group which attracts water, and long hydrocarbon chain tails which repel water. A good way for the early life (RNA, DNA, Proteins) to separate themselves from the compounds that could damage them was to keep those compounds away. This was achieved using two layers of these phospholipids aka a phospholipid bilayer (also shown above). The water repelling portions (the hydrocarbon tails) face each other (because they hate water) which allows the charged water loving phosphate heads to contact it on either side. With these you can create pockets of liquid that are sequestered and protected from the surrounding liquid, and it's exactly these sorts of bilayers which contained RNA, DNA and Proteins inside becoming the precursors to cellular life we know and love (and are still used by) today.

This Seems Fine and Good, but Can Anyone Prove Any of it?

For a long time the answer to that question was no. This is why this was called the RNA world hypothesis, and not the RNA world theory. Nobody came up with a way to test the hypothesis, and as we have discussed previously, something can’t be a scientific theory unless there is data to support it! So into the annals of science the RNA world hypothesis went, sure it was a cool idea and fun to think about but that’s about as far as things could go…

Until Now

In the article “RNA–DNA Chimeras in the Context of an RNA World Transition to an RNA/DNA” Jesse V. Gavette et al. describe work they set out to do in an attempt to look at how one homogeneous set of nucleic acids (RNA) could evolve another homogeneous set (DNA). They discuss how if evolution from RNA to RNA + DNA did happen, then there should be a presence of RNA/DNA hybrids, or some combination therein of RNA and DNA together, as their bases are complementary (and the majority of which are even shared eg. Adenine, Cytidine and Guanidine):

(Source 1) (Source 2)

Only Thymine is unique to DNA and Uracil is unique to RNA. Lots of sharing going on there at least with the bases. We all know that the sugar component is different between RNA and DNA.

Previous works looking at these sorts of hybrids didn’t identify any clear reason why a mixed RNA/DNA population would be selected against based on the strengths of the interactions between the bases among other things. (Citation) Basically, if the RNA world hypothesis were plausible we should see a lot more RNA/DNA hybrids around rather than RNA usually being separate and the DNA double helix also being separate.

The researchers of the current article decided to look into this a little bit more carefully, and created a variety of artificial constructs containing differing ratios of RNA:DNA ranging from 100:0 to 100:0 and varying mixed ratios in between. What the authors found was interesting and unexpected. They observed decreased stability for the mixed nucleic acids, where the least stable nucleic acids were those that contained a 50:50 mixture of RNA and DNA. The researchers observed what others hadn't been able to see in the past, that RNA and DNA really don’t want to mix. It looks like the differences between the sugars in the backbone of RNA just don't like to mix with the sugars of the DNA backbone (interesting considering they differ only by one -OH).

This is really important for the RNA world hypothesis, because what it means is that were DNA to be evolved later after RNA. These RNA/DNA hybrids would indeed form, and they can exist. However, there is selective pressure against the mixed populations! This means that over time (say hundreds of millions of years…you know… the time scale of evolution) that those mixed populations would favor being two discrete populations one of RNA by itself, and another of DNA by itself. Rather than disproving the RNA world hypothesis, they ended up showing evidence in its favor.

TL;DR

The RNA world hypothesis has always been a fun topic to discuss, but it was largely considered an oddity (that's just a nice way of saying trash). Previous research indicated that RNA/DNA hybrids were stable, were they to have formed through evolution we would expect to find them playing a more prominent role in biological processes. They don’t so people still felt that the two molecules evolved independently. For the RNA world hypothesis to not be garbage (scientifically speaking of course) these sorts of RNA/DNA hybrids would have had to exist at least in the interim. The research in the article I have discussed illustrates that while RNA/DNA mixtures are possible, they are less stable then either RNA or DNA alone. This selective pressure (the reduced stability) would be enough to result in the tendency to form two discrete populations even if were to have come first. This research has pulled the RNA world hypothesis of the dusty shelf of fun but not able to be proven, and moved it one leap forward toward entirely possible.

Way way back, many eons ago. It looks like your most distant of relatives just might have been a self-replicating piece of RNA. How does that make you feel? I know how it makes me feel. Excited. Because it’s pretty darn cool. It's just too bad Carl Woese didn't get to live long enough to see just how right he might have been.

Source

That's the smile of a man who knew he was right. RIP Dr. Woese, you were quite the visionary.

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