To explain the origin of life, scientists seek to explain the origin of its components. The three most important of these are RNA, DNA, and proteins.
Just about all life today uses DNA to encode its genetic information. The only exception are viruses that use a single-stranded version of DNA, known as RNA. The rest of us have RNA in our cells as well, but it carries out other functions. Some RNA molecules are copies of genes that our cells use as templates to build proteins; others can silence genes or act as sensors or help to build proteins. As I wrote in an essay published in Science in January, this sort of evidence has led a number of researchers to argue that life as we know it, with DNA, RNA, and proteins, started out with just RNA. In the so-called RNA world, this versatile molecule acted both like DNA (storing genetic information) and proteins (carrying out chemical reactions, such as building new RNA molecules). It’s a big hypothesis, and certainly not simple to test. No one has discovered any truly free-living RNA-based organisms, and so if the RNA World did exist once, its inhabitants may have been driven extinct when some of them gave rise to DNA-based life. And there’s another big question: if there was RNA-based life, where did the RNA come from?
One possibility is that the raw ingredients on the early, lifeless Earth reacted with each other and produced RNA. For 40 years, scientists have been investigating the chemistry of those ingredients–stuff like formaldehyde and cyanide–to see if they could indeed combine into the first biological molecules. It’s been quite a struggle–but it turns out that it was a struggle the scientists brought upon themselves. They tried to make RNA the obvious way, but nature doesn’t care what we consider obvious.
RNA is a word-like molecule, with four different letters that can be combined into a vast variety of strings. Each letter is called a ribonucleotide. It has two parts. One part lets the ribonucleotide bind to the ribonucleotides on either side, to form a backbone. It’s made of phosphate and a sugar called ribose. The other part is the nucleobase, which comes in four different forms and encodes genetic information.
So it seemed obvious that if indeed RNA emerged on the early Earth, its two parts must have emerged first. Scientists discovered reactions that suggested that nucleobases can indeed form from prebiotic molecules, as can the riboose-phosphate backbone. But when it came time to join together the two parts, the scientists hit a wall. The two molecules just don’t like each other much. Their dislike of each other led some scientists to look into the possibility that life did not start out with RNA, but with another molecule that doesn’t exist anywhere on Earth today. Later, RNA replaced that mystery molecule, and then later still DNA and protein evolved.
But as I explained in my Science essay, University of Manchester John Sutherland thought it was too soon to rule out the possibility that life had started out with RNA. He began to look for other routes from prebiotic chemistry to RNA besides the obvious one. Today, in Nature, he and his colleagues report that they found it.
In their paper, they published a kind of chemical road map that sums up what they did. Don’t be put off–I’ll explain the lay of the land below.
The blue arrows represent the obvious route to RNA, going from prebiotic compounds (marked here by 7,8, and 10) to nucleobases (3) and ribose (4). And the big red X shows the point at which this route fails.
Sutherland and his colleagues started with the same ingredients, but cooked them in a different recipe, marked in green. Instead of trying to build the two parts independently, the scientists instead built a single molecule that had more and more components of the two parts already in place. They used just four reactions, all of which worked efficiently, to get one of the four ribonucleotides, known as cytidine. At the end of the process, the scientists zapped the mix with ultraviolet light (something that would be easy to come by on the early Earth, unprotected by an ozone layer). They eliminated some of the unwanted side products and turned some of the cytidine into another unit of RNA, known as uracil.
In an accompany commentary, Jack Szostak of Harvard calls this experiment a “tour de fource.” Of course, it doesn’t answer all the questions about the RNA World–for starters, scientists still have to synthesize the other two letters in RNA’s alphabet. But it does show how careful scientists must be not to declare things impossible. Sometimes they just need to redraw the map.
Sources:
Powner et al, “Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions,” Nature 2009, 459:239 doi:10.1038/nature08013
Jack Szostak, “Systems chemistry on early Earth,” Nature 2009, 459:171
[Image: MuppetWiki]
May 13th, 2009 at 2:33 pm
Carl,
This is a wonderful summation. When I was in High School in the 70s the work of Sidney Fox suggested that prebiotic amino acids could have formed proteinoids. Proteinoids in water form globular structures called microspheres that show many of the properties of living cells.
I wonder if such microspheres could have enclosed the primitive RNA molecules, allowing them the space and stability for their necessary catalytic reactions?
Richard
May 13th, 2009 at 2:58 pm
[...] worked in that kitchen May 13, 2009 — Richard In The Prebiotic Kitchen: [Via The Loom] To explain the origin of life, scientists seek to explain the origin of its [...]
May 13th, 2009 at 4:46 pm
Hi, Carl, This is very exciting. It might be an evolutionary companion to an article by Robert Shapiro in the June, 2007 Scientific American. Shapiro outlines an “energy-driven” initiation of life, which he terms “metabolism first.” Droplets bounded by primitive membranes (perhaps the microspheres described above by Richard Gayle) acquire useful compounds that react to supply energy to a slowly evolving series of growth stages. These droplets acquire compounds at random from the environment, some useful some not. Perhaps some of the randomly acquired compounds could be the ones you describe here.
May 13th, 2009 at 6:17 pm
Hi Carl,
Thanks for an interesting piece. I’m confused in your initial description of RNA as a sugar combining with a phosphate compound– I see the Ribose sugar in your diagram, but the amino compound “nucleobase” hasn’t a phosphate group or phosphorus atom to be seen. My organic chemistry is very rusty, but is there something I’m missing?
May 13th, 2009 at 7:00 pm
Excellent summation of the research.
With all due respect to Dr. Robert Shapiro, who has been commentating on this recently published work, and who advocates the ‘Metabolism’ first hypothesis, this is a piece of work that is purely experimental with little or no hypothetical conjecture.
Is it not true that we have to base science on facts? It is very easy to be cynical and criticise work, but if one does need to oppose one theory and propose an alternative, as Dr Shapiro has done in this case, should it not be backed up with some sort of evidence?
Indeed it is true that Professor Eschenmoser once stated, and forgive me if it is slightly misworded, that:
‘The origins of life cannot be rediscovered, it must be reinvented’.
Let us say that this work is an example of what MAY have happened. What has been shown in this research may have not been the case. We will never know, but it is a strong contribution of what may have taken place on primordial earth. I call on those who would like to contest the ‘RNA world’ or an ‘RNA world + X’ hypothesis to disclose some sort of evidence otherwise.
May 13th, 2009 at 7:05 pm
Understanding how life emerged on Earth is one of the greatest challenges facing modern chemistry. A new way of looking at the synthesis of RNA sidesteps a thorny problem in the field.
They are on a fool’s errand.
Cosmic Ancestry (panspermia) answers most of the questions WRT the origin of life on earth.
May 13th, 2009 at 7:19 pm
What do you mean by ’side step’? Do you mean that we should take ribose, a nucleobase, and phosphate and then stick them together?
It’s been tried and it doesn’t work. Which means it happened in another way. This work isn’t a ’side step’, it’s an alternative way of the first few steps to getting to RNA.
Panspermia? Please provide some sort of evidence. An iota of it would be a start.
May 13th, 2009 at 7:21 pm
I haven’t read the article yet. I can’t concentrate enough. The duck on the right side of the first diagram keeps distracting me.
May 13th, 2009 at 9:05 pm
“Panspermia? Please provide some sort of evidence. An iota of it would be a start.”
Start here:
http://www.panspermia.org/archindex.htm
That should keep you busy for a while!!
May 13th, 2009 at 9:31 pm
Panspermia = “it’s turtles all the way down”
May 13th, 2009 at 9:41 pm
Panspermia? That doesn’t answer the question. It just moves it.
May 13th, 2009 at 9:48 pm
[...] Carl Zimmer does a great job of explaining it on his blog, “The Loom” The comments and bibliography there are worth checking out as well. [...]
May 13th, 2009 at 11:42 pm
Captain Kidd, that website appears to just link to whatever the person who maintains it thinks supports his position regardless of what is linked to actually says. I see a lot of titles of recent journal articles that have nothing to do with panspermia, and can only be linked to it by very contorted thinking. Frankly, it reeks of a person who has decided what the absolute truth is, and thus tries to fit the world to that notion. That isn’t science – it is bad post hoc reasoning of the sort found in creationism and conspiracy theories. Try linking to some peer-reviewed papers that explicitly test predictions from panspermia and give actual evidence for it.
And in any case, SteveC is correct: you are just moving the question. Life had to start somewhere, and wherever it started, the question remains as to how. Panspermia does not even start to get at that question (even when it is a seriously address hypothesis, which it certainly is not at that website to which you referred everyone).
May 14th, 2009 at 3:30 am
Still not convinced by Panspermia. I’ve just visited the wired.com website, and it’s full of comments about this work being orchestrated by Obama…….please.
This work has been ongoing for years. The conspiracy theories merely make me laugh, and smells of pathetiscm (even though it’s not a real word I shall use it here). This is a bit like a bomb dropping on the heads of a creationist, metabolist or whatever other theory you believe in.
Give me some hard facts, I’m open minded and ready to be convinced.
May 14th, 2009 at 12:12 pm
[...] till now. John Sutherland has come up with a chemical route by which RNA synthesis can take place. Carl Zimmer of Discover magazine does a great job of summarizing, as usual. Also, check out the article in NY times by Nicholas [...]
May 14th, 2009 at 12:31 pm
[...] I love this stuff: [...]
May 14th, 2009 at 6:39 pm
Thanks for this one, Carl! I love the “origins” stuff. Your proto-ribosome and viroid pieces were fantastic, and this one’s a real gem. Keep ‘em coming!
May 15th, 2009 at 10:01 am
[...] In The Prebiotic Kitchen | The Loom | Discover Magazine (tags: genetics research) [...]
May 15th, 2009 at 7:04 pm
Nice writeup!
One hypothesized task I’ve seen is that RNA acts to concentrate and activate mono- or diamino acids, which likely preceded it. It is probable that in prebiotic chemistry a little bit of ‘everything’ happened simultaneously.
That is by the way a prediction that this result tests positive for as phospate isn’t just an afterthought but contribute to the result. In the same sense, what is then less promising is that I hear they still had to purify in between steps.
Now I wonder if they could simplify (well, sort of since 4 reactions is really simple) by using glycine instead of ribose as backbone. GNA is a putative pre-RNA compound, doing the same task with an even simpler molecule. Again, perhaps initially both GNA and RNA was in play.
May 16th, 2009 at 10:21 am
This reminds me of how the initial attempt at synthesising vitamin B12 failed due to the wrong choice of retrosynthesis.
Years of work making two halves that then could not be joined.
May 16th, 2009 at 10:34 am
Agreed about retrosynthetic analysis. The problem with the earlier attempts to make ribonucleotides has been retrosynthetic analysis. Yes, RNA is structurally and constitutionally more difficult at first look, merely because the number of atoms in it, as well as the stereochemical complexity (i.e it’s three dimensional shape), but in terms of chemistry so far it has been demonstrated to be generated quite efficiently. GNA has yet to be demonstrated to be created prebiotically. Just because something looks simple, doesn’t mean it’s easier to make. Likewise, the same problem exists with other ‘minimal’ nucleic acids such as PNA and TNA.
With respect to RNA and amino acids, a nice paper was published by Sutherland and Mullen I think in 2007 in a german chemistry journal, Angewandte Chemie, where they activate ribonucleotides, as well as make amino acid amides.
May 16th, 2009 at 8:13 pm
[...] And so one more complex structure falls prey to nature’s cunning. For commentary, see here and here. [...]
January 10th, 2010 at 2:51 pm
Unbelievable! Origin Of Life Pre-Metabolism?
The Wheel has Just Been Reinvented!
Read All About It!
What Came First in the Origin of Life? New Study Contradicts the ‘Metabolism First’ Hypothesis
http://www.sciencedaily.com/releases/2010/01/100108101433.htm
Dov Henis
(Comments From The 22nd Century)
Updated Life’s Manifest May 2009
http://www.the-scientist.com/community/posts/list/140/122.page#2321
28Dec09 Implications Of E=Total[m(1 + D)]
http://www.the-scientist.com/community/posts/list/184.page#4587
Cosmic Evolution Simplified
http://www.the-scientist.com/community/posts/list/240/122.page#4427
PS: Just reflect about sleep and chirality… DH
February 9th, 2010 at 10:46 am
Life IS INDEED An RNA World
Genomes Are RNAs’-Made Patterns-Manuals
“Repeats protect DNA”
http://www.the-scientist.com/blog/display/57135/
“More On Evolution In The Still RNA World”
http://www.the-scientist.com/community/posts/list/260/122.page#4818
Fitting together the pieces of the “still an RNA world” puzzle ?
- Rational probability and possibility that the initial, independent pre-biometabolism direct sunlight-fueled genes (life) were RNAs, who evolved their DNA-images as operational patterns-manuals libraries, and celled and genomed them. They most probably synthesized (and nucleusized) their DNAs manual libraries as their functional organs, to serve as their environmentally stabler than RNA, than themselves, works memory cores.
- Rational possibility that ALL RNAs represent the original archae-genes that since their (life) genesis have been and still are the primary actors, assessors, messengers, operators of all life processes.
- Rational possibility that the RNAs are the environmental feedback communicators to, and modifiers of, the genomes, that the RNAs are the effectors of the desirable biased genes expressions modifications, of enhanced energy constraining for survival.
Dov Henis
(Comments From The 22nd Century)
28Dec09 Implications Of E=Total[m(1 + D)]
http://www.the-scientist.com/community/posts/list/184.page#4587
Cosmic Evolution Simplified
http://www.the-scientist.com/community/posts/list/240/122.page#4427