The Origins of Life, Part I: Introductions and The RNA World

This is the first of a series of posts discussing the biophysical aspects of the origins of life on Earth. In this first post I’ll broadly introduce the origins of life field of research, setting the stage for the next two posts, in which I’ll talk about my previous research project involving thermal gradients. It’s a really exciting set of ideas and I hope that this series will encapsulate the main ideas in an accessible fashion.

As the name suggests, origins of life research deals with studying the possible mechanisms by which life began on the Earth. As a field, it has immediate appeal – if we consider all life as an unimaginably vast, unbroken chain of evolutionary history, it’s only natural to then ask the obvious question of how it all got started.

geological_time_spiral
Visualizing the evolutionary history of life on Earth.

Now that’s quite the grand question, but rather intractable. It’s helpful to begin with some less ambitious questions: 1) when did life start? 2) where did it start? and 3) how did it evolve into its current form? Much of this introductory material can be found in this excellent review by Leslie Orgel1.

There is actually quite a general consensus on the first point. Most scientists agree that the Earth is slightly more than 4.5 billion years old, and that life probably began around 3.8 billion years ago. The earliest fossils date back to around 3.5 billion years, giving a margin of opportunity of a few hundred million years for life to have started on Earth. So, the question of when life began is more or less settled, but that’s only a fraction of the picture. What we care more about is the method by which it all got started, which would give us more insight into the sorts of processes that would lead to the spontaneous creation of life.

Which brings us to question number two. Where did life start? Studies suggest that the early Earth was capable of synthesizing the primordial building blocks of life – amino acids, nucleotides, and so on. The classic Miller-Urey experiment2, although somewhat dated, provided persuasive arguments that the early Earth’s atmosphere could produce such building blocks. Others argue that life began in deep-sea hydrothermal vents3. Still others subscribe to the theory that these building blocks were transported to the Earth from outer space, on meteorites carrying cargo rich in biochemical compounds. Unfortunately, the nature of origins of life research is rather like a detective story – we possess an abundance of evidence in the form of current-day biology, but can only guess as to what actually happened 3.5 billion years ago. Solid proof, in that regard, would be incredibly difficult to discover.

Luckily, question three can be largely decoupled from question two. Regardless of its source, it’s important to study how life progressed from its original state. As far as we know, all life on Earth shares a common biochemical framework of information storage, replication, and processing known as the Central Dogma. That is, the stuff of life is written in DNA, transcribed for use in RNA, and translated into function in proteins. The seemingly universal nature of this system strongly suggests that all life shares a last-common ancestor (LCA), some primordial creature that outcompeted all the other possible candidates in the early Earth.

central_dogma_of_molecular_biochemistry_with_enzymes
Figure by Dhorspool, distributed under a CC BY-SA 3.0 license.

How did we get from the LCA to the present? The Central Dogma – the framework of contemporary life – is a highly intricate system that is the byproduct of billions of years of evolution. It’s almost certain that the LCA did not have such a refined mechanism; instead, its structure was likely rather ill-suited for survival, a crude version of life in a harsh and unforgiving early Earth. If we strip away the more ancillary features of life, what core components remain as necessary requirements of life?

In general, there are three classes of function that are required for a minimal realization of life: information, metabolism, and protection. Information is the most obvious category – without information storage and replication (achieved today by DNA and RNA), we wouldn’t have the stuff of life that gets passed down generation after generation. Metabolism, the conversion of external material into usable energy, is needed to keep the engine of life running. And finally, some sort of compartmentalization is needed to shelter life from a dangerous environment – without membranes, for example, a bacterium’s precious genome would be subject to harsh degradation.

Each function is different enough that many scientists think they arose independently. Once one of these functions arrived as a primordial lifeform, the stage was set for the other two functions to be eventually incorporated. In this post, I’ll be mostly focusing on the possibility where “information-first” hypothesis, since it’s most relevant to the concept of thermal gradients in the origins of life. Nevertheless, the question of which biological function appeared first – information, metabolism, or compartmentalization – is still unsettled.

What does an information-first world look like? The main idea is that the Central Dogma – life consisting of DNA, RNA, and proteins – is highly efficient but also redundant when considering life from a minimalist perspective. It turns out that RNA is the only absolutely required piece of the system. It stores information, albeit in a far less stable form than DNA, and also is capable for catalyzing simple chemical reactions. It can also emulate protein function – in 1982, scientists discovered the ribozyme, a complex RNA structure that was capable of catalyzing simple chemical reactions4. Subsequent discoveries found that ribozymes could be capable of self-replication, which lent great support for the information-first hypothesissince it solved the chicken-and-egg problem of how to replicate nucleic acids without the help of proteins.

With these facts in hand, the idea of the RNA world was born. The theory posits that the first quasi-lifeforms consisted of precious strands of RNA that, by chance, unlocked the ability to self-replicate in a crude fashion. Without contemporary luxuries such as cell membranes or specialized proteins, these primordial lifeforms would have find life to be very difficult, but eventually the forces of chance and natural selection would have produced a viable realization that would become the LCA. This story possesses strong evidence, as studies have shown that the synthesis of RNA monomers in the early Earth was highly possible – it appears that chance alone could have produced short, crude strands of RNA molecules6.

So, where do we stand? Our proposed explanation for the origin of life on Earth begins with simple nucleotides naturally being produced in the early Earth, forming small strands of RNA that achieved the ability to self-replicate, protect themselves with simple membranes, harness energy through metabolism, and eventually evolve to incorporate DNA and proteins to form the highly sophisticated version of life as we know it.

If this sounds a bit optimistic to you…that’s because it is. There are a host of problems with this narrative, mainly involved in the intermediary transition from small strands of RNA to complicated ribozyme structures. Luckily, some of these problems possess elegant solutions in the form of nonequilibrium systems with thermal gradients, a concept that I’ll highlight in the next blog post.

 

References:

  1. Orgel L., The origin of life – a review of facts and speculations. Trends in Biochemical Sciences 23 (12): 491-495 (1998).
  2. Miller S. L., A production of amino acids under possible primitive Earth conditions. Science 117, 528–529 (1953).
  3. Wächtershäuser G., Before enzymes and templates: theory of surface metabolism. Microbiol. Rev. 52, 452–484 (1988).
  4. Kruger K., Grabowski P.J., Zaug A.J., Sands J., Gottschling D.E., Cech T.R., Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 31 (1): 147–57 (1982).
  5. Paul N., Joyce G., A self-replicating ligase ribozyme. PNAS 99 (20) 12733–12740 (2002).
  6. Powner, M. W., Gerland, B. & Sutherland, J. D. Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature 459, 239–242 (2009)

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