The glass RNA factory

A couple of months ago, I wrote about a discovery that has startling (and encouraging) implications for the search for extraterrestrial life -- that amino acids, the building blocks of proteins, are so easy to form abiotically that they are common even in interstellar dust clouds.

Well, because of my twin-brudda-from-anudda-mudda, the wonderful writer and blogger Andrew Butters, I found out that a new bit of research has shown that another piece of biochemistry -- RNA -- is equally easy to make in large quantities.

If anything, this is even more exciting to us aliens-in-space aficionados than the amino acid research was, because the model for the origins of life on Earth that is now virtually universally accepted is called "RNA world."  The idea has been around since the early 1960s, and simply put, it's that the first nucleic acid type to form in the early oceans was not DNA, but RNA.  At first this model met with considerable skepticism.  One common criticism was that the only organisms that encode their genome as RNA are certain viruses (such as the common cold, flu, rabies, mumps, measles, hepatitis, and COVID-19); all other organisms encode their genomes as DNA.  The second is that RNA has a tendency to be unstable.  It's a single helix; the shape resembles a spiral with short spokes sticking out at angles along its length, and that open shape allows it to be attacked and broken down readily by solvents (including water).

[Image licensed under the Creative Commons DataBase Center for Life Science (DBCLS), 201904 RNA, CC BY 4.0]

Two subsequent discoveries tilted biochemists toward accepting the RNA world model.  First, it was found that there are stable forms of RNA, such as transfer RNA, that are able to protect themselves from breakdown by having "hairpin loops" -- places where the helix doubles back and bonds to itself through complementary base-pairing, just like DNA has.

[Image licensed under the Creative Commons Vossman, Pre-mRNA-1ysv-tubes, CC BY-SA 3.0]

The second discovery was that RNA is autocatalytic -- pieces of RNA can actually feed back and speed up the reactions that form more RNA.  DNA doesn't do this, which was a major stumbling block to figuring out how the first self-replicating DNA formed.

So most folks are convinced that RNA was the first genetic material, and that it was only superseded by DNA after first double-stranded RNA formed, and then there was a chemical alteration of the sugar in the backbone (deoxyribose for ribose) and one of the nitrogenous bases (thymine for uracil).  But this only shoved the basic problem back one step.  Okay, RNA came before DNA; but what made the RNA?

We've known for ages, because of the stupendous Miller-Urey experiment, that making nucleotides -- the building blocks of both RNA and DNA -- is easy in the abiotic conditions that existed on the early Earth.  But how did link together into the long chains that form the structure of all functional RNA?

The new research indicates that it's amazingly simple -- all you have to do is to take the solution of nucleotides, and allow it to percolate through the pores of one of the most common rocks on Earth -- basaltic volcanic glass.

This stuff is kind of everywhere.  Not only is ninety percent of all volcanic rock on Earth made of basalt, it's also common on the two other rocky worlds we've studied -- the Moon and Mars.  "Basaltic glass was everywhere on Earth at the time," said Stephen Mojzsis, of the Budapest Research Centre for Astronomy and Earth Sciences, who co-authored the study.  "For several hundred million years after the Moon formed, frequent impacts coupled with abundant volcanism on the young planet formed molten basaltic lava, the source of the basalt glass.  Impacts also evaporated water to give dry land, providing aquifers where RNA could have formed."

Basalt also contains two ions that the team showed were critical for forming the RNA nucleotides and then linking them together -- nickel and boron.  The experiments they ran showed that all you had to do was pour the nucleotide slurry over the basaltic glass, and wait -- and voilà, in a day or two you had 100- to 200-subunit-long chains of RNA that look exactly like the kind you find in living things.

Given basalt's ubiquity on rocky planets, this makes it even more likely that there is life elsewhere in the universe, and that its biochemistry might have some striking overlap with ours.  Exciting stuff.

So it looks like the quote from the wonderful movie Contact might well turn out to be prescient.  "The universe is a pretty big place. It's bigger than anything anyone has ever dreamed of before. So if it's just us... seems like an awful waste of space."

**************************************

A door into RNA world

[N.B.: This post is a little on the technical side, if you're not a biology type.  Trust me, the work is worth it, because what these people have discovered is stupendous.]

I had the experience yesterday of stumbling on an article published in Nature this week that, from the title, seemed like something that could only interest biochemistry geeks.

Then I started reading it, and I had to pick my jaw up off the floor.

Before I tell you about the paper, a little background.

Most laypeople know that genes are basically stretches of DNA, and that DNA is a double helix made of chains of smaller molecules called nitrogenous bases, of which there are four -- adenine, thymine, guanine, and cytosine.  (A, T, G, and C for short.)  Because the bases always pair the same way (A to T, C to G), it allows for DNA to replicate itself.

So far, so good.  But how do you get from a gene to a trait?  It took a long time to figure this out, and there's still work being done on how genes switch on and off during development.  But a simplified explanation goes like this:

The first step is that one gene (a piece of DNA) is copied into a similar, but not identical, chemical called RNA.  (This is called transcription.)  RNA is a single helix, so only one side of the DNA gene is copied; the other side only exists so the DNA can be replicated.  Then the RNA goes to a cellular structure called a ribosome, where the base sequence is read in threes (a group of three is a codon), and each trio instructs the ribosome to bring in a specific amino acid.  The amino acids dictated by the codon sequence are linked together into a protein, and those proteins directly generate the trait.  (This is called translation.)  Every trait is basically produced this way, whether it's something simple like skin color, or the interaction between the thousands of genes and proteins that it takes to generate a functioning human heart.

Okay, gene > RNA > protein > trait.  The sequence is so ubiquitous that it's been nicknamed The Central Dogma of Molecular Genetics.

[Image licensed under the Creative Commons  , Pre-mRNA-1ysv-tubes, CC BY-SA 3.0]

But here's the problem.  When life first began, how did the process get started?

The problem isn't the building blocks; given the conditions that we're virtually certain existed on the early Earth, all of the pieces -- the bases, the sugars that make up the backbone of both DNA and RNA, the amino acids -- form spontaneously and abundantly.  They will even link up to form chains on their own.  It's likely that any Earthlike, water-containing planet has plenty of all the biochemical bits and pieces.

But how do you get from a particular RNA to a particular protein?  Remember, it's the sequence of bases in RNA that determines the sequence of amino acids in the protein, but to read the RNA sequence and assemble those amino acids requires a lot of cellular machinery -- first and foremost the ribosome.

Which is itself made of RNA.

So it seems like the first life had to pull itself up by its own bootlaces.  Put succinctly, to do transcription and translation, you need to have the mechanisms of transcription and translation already in place.

Or at least, that's what I thought until I read this paper.

Enter the team led by Felix Müller of Ludwig-Maximilians-Universität in Munich, Germany, and their paper "A Prebiotically Plausible Scenario of an RNA-Peptide World."  Here's how the paper begins, with a couple of parenthetical notes added by me:

A central commonality of all cellular life is the translational process, in which ribosomal RNA catalyses peptide [i.e. protein] formation with the help of transfer RNAs, which function as amino acid carrying adapter molecules.  Comparative genomics suggests that ribosomal translation is one of the oldest evolutionary processes, which dates back to the hypothetical RNA world [the theory that the earliest self-replicating genetic molecules were RNA, not DNA, which is generally accepted in the scientific world].  The questions of how and when RNA learned to instruct peptide synthesis is one of the grand unsolved challenges in prebiotic evolutionary research.

The immense complexity of ribosomal translation demands a stepwise evolutionary process.  From the perspective of the RNA world, at some point RNA must have gained the ability to instruct and catalyse the synthesis of, initially, just small peptides.  This initiated the transition from a pure RNA world into an RNA–peptide world.  In this RNA–peptide world, both molecular species could have co-evolved to gain increasing ‘translation’ and ‘replication’ efficiency...

We found that non-canonical vestige nucleosides [i.e. unusual bases which are still part of some structures made of RNA, but aren't on the list of the four standard bases], which are key components of contemporary RNAs, are able to equip RNA with the ability to self-decorate with peptides.  This creates chimeric structures, in which both chemical entities can co-evolve in a covalently connected form, generating gradually more and more sophisticated and complex RNA–peptide structures...  We... found that peptides can simultaneously grow at multiple sites on RNA on the basis of rules determined by sequence complementarity, which is the indispensable requirement for efficient peptide growth.

Which is way more dignified than what I'd have written, which is, "Holy shit, we just figured out how gene expression evolved!"

In my AP Biology classes, I ended the unit on evolution with a list of some of the questions that evolutionary theory had not yet solved, and the origins of gene expression and protein synthesis topped the list.  It looks like that one might now be checked off -- which, if my assessment is correct, should put Müller and his team in contention for this year's Nobel Prize in chemistry.

I find it so fascinating that there are still some of the Big Questions out there, and that scientists are actually making inroads into answering them.  Good science doesn't just say "it's a mystery" and forthwith stop thinking.  We're gradually chipping away at problems that were thought to be intractable -- in this case, giving us insight into how life began on Earth four billion years ago.

**************************************

Life out of catastrophe

After yesterday's post about mysterious explosions in distant galaxies, today I want to look at a colossal explosion that happened much, much closer to home -- and may have jump-started life on Earth.

In a paper by Steven Benner of the Foundation for Applied Molecular Evolution in Alachua, Florida, presented at a conference last fall in Atlanta, we find out that there's geological evidence that early in Earth's history, there may have been a collision with an enormous object -- by some estimates, the size of the Moon -- that drastically altered the atmosphere.  4.47 billion years ago, only sixty million years after the Earth coalesced from the ring of planetary debris where it originated, it was struck so hard by planetoid that water molecules were ripped apart into oxygen and hydrogen, and superheated metallic debris was flung into the air and generated a torrential rain of molten iron.

Artist's conception of what the collision might have looked like from space

As the atmosphere (and everything else) cooled, the highly reactive oxygen bound to the iron, forming a thick layer of iron (and other metal) oxides that explains their prevalence in the Earth's crust today.  More interesting still is that the collision left behind the hydrogen in the atmosphere.  This created what is called a reducing atmosphere -- a collection of gases with an abundance of free electrons, essentially the opposite of what we have today (an oxidizing atmosphere, where oxygen and other electronegative elements mop up any available electrons, making organic matter and other reduced compounds fall apart).

The reducing atmosphere, Benner says, stuck around for two hundred million years, and it was during this time that the first organic compounds were formed.  This lines up neatly with the famous Miller-Urey experiment, where biochemists Stanley Miller and Harold Urey of the University of Chicago showed back in 1952 that in the presence of reducing gases and a source of energy, organic compounds formed readily, including DNA and RNA nitrogenous bases, amino acids, and simple sugars.

Benner believes that the critical one was RNA.  RNA is (as far as we know) unique in that it can not only replicate itself, it's autocatalytic -- it can catalyze its own reactions.  This pull-yourself-up-by-your-shoelaces ability is why a lot of scientists believe that the first genetic material was RNA, not the (currently) more ubiquitous DNA.  And Benner's theory about how the reducing atmosphere was generated explains not only how the building blocks of RNA could have formed, but why the Earth's atmosphere was reducing in the first place.

Benner believes the key is a set of biochemical reactions that involves repeated wetting and drying, along with interaction of the oxygen-free atmosphere with sulfur-containing gases released from volcanic eruptions.  He has demonstrated that in these conditions, formaldehyde -- CH₂O, one of the simplest organic compounds, would form "by the metric ton."  From there, reactions with the sulfur-bearing gases produced hydroxymethanesulfonate, which reacts readily to form glyceraldehyde (a simple sugar) and the four bases of RNA, adenine, cytosine, guanine, and uracil.

Once that happens, the autocatalytic ability of RNA means you're off to the races.  As Richard Dawkins pointed out in his tour-de-force The Blind Watchmaker, if you have two things -- an imperfect replicator, and a selecting mechanism -- you can generate order from disorder in the blink of an eye.  "[M]any experiments have confirmed that once RNA chains begin to grow, they can swap RNA letters and even whole sections with other strands, building complexity, variation, and new chemical functions," said science journalist Robert F. Service, writing for Science magazine.  "[T]he impact scenario implies organic molecules, and possibly RNA and life, could have originated several hundred million years earlier than thought.  That would allow plenty of time for complex cellular life to evolve by the time it shows up in the fossil record at 3.43 billion years ago."

This research not only confirms what Miller and Urey showed in their landmark experiment 67 years ago, but lines up beautifully with what is known from studies by geologists of the earliest rocks.  As for Benner, he's ready to put aside any doubt.  When Ramon Brasser, paleogeologist at the Tokyo Institute of Technology, laid out a timeline of the early Earth in his talk at the Atlanta conference, Benner asked him when the atmosphere would have likely dropped below a temperature of 100 C, the boiling point of water.  Brasser indicated a point about fifty million years after the impact with the planetoid.

"That's it, then!" Benner said excitedly, pointing to a spot at about 4.35 billion years ago on the timeline.  "Now we know exactly when RNA emerged. It's there—give or take a few million years."

********************************

This week's Skeptophilia book recommendation is a little on the dark side.

The Radium Girls, by Kate Moore, tells the story of how the element radium -- discovered in 1898 by Pierre and Marie Curie -- went from being the early 20th century's miracle cure, put in everything from jockstraps to toothpaste, to being recognized as a deadly poison and carcinogen.  At first, it was innocent enough, if scarily unscientific.  The stuff gives off a beautiful greenish glow in the dark; how could that be dangerous?  But then the girls who worked in the factories of Radium Luminous Materials Corporation, which processed most of the radium-laced paints and dyes that were used not only in the crazy commodities I mentioned but in glow-in-the-dark clock and watch dials, started falling ill.  Their hair fell out, their bones ached... and they died.

But capitalism being what it is, the owners of the company couldn't, or wouldn't, consider the possibility that their precious element was what was causing the problem.  It didn't help that the girls themselves were mostly poor, not to mention the fact that back then, women's voices were routinely ignored in just about every realm.  Eventually it was stopped, and radium only processed by people using significant protective equipment,  but only after the deaths of hundreds of young women.

The story is fascinating and horrifying.  Moore's prose is captivating -- and if you don't feel enraged while you're reading it, you have a heart of stone.

[If you purchase the book from Amazon using the image/link below, part of the proceeds goes to supporting Skeptophilia!]