Biology, chemistry, and physics often overlap in topics they cover, necessitating collaborations across fields for this or that experiment. There are crossover fields that fall more on one side or the other, often depending on the particular technologies used in that field. But there is rarely a more intertwined field of study than that which seeks to decipher the origin of life itself by the combination of physical and chemical processes to make a biological phenomenon. That would be the research that goes into abiogenesis.

The scientific community knows quite a bit about life after the fact, how it functions, propagates, and survives even the most improbable mass extinction events, though there remain plenty of surprises to uncover. However, while we do understand many, if not most, of the pieces that make up that original formation of life, it is the interconnecting paths between each step that still has scientists pursuing answers.

A primary fragment under investigation is how the earliest single celled life forms (just bubbles of connected molecules, really) moved from the initial formation of RNA to the replication of that RNA and, thereafter, themselves. This is a critical point to figure out if the “RNA World” hypothesis is to be proven and, by all accounts, the evidence continues to strongly suggest its accuracy.

Past Experiments

Some of the first experiments in this regard from the 90’s tried to use naturally forming self-splicing introns or ribozymes (RNA able to act as an enzyme thanks to its structure) focused on ligation. The drawback to these early designs though is that they needed blocks of RNA at least 8 nucleotides long for replication to happen and that construction would have to occur naturally and repeatedly. The likelihood of that happening was minuscule, even over millions of years of attempted time.

Over the past few earthly cycles, new attempts have zeroed in on new ribozyme candidates that act as RNA polymerase for building and replicating RNA and can use simple building blocks in the form of ribonucleoside triphosphates (NTPs) that are far shorter in length. These were a much more doable length and design to occur spontaneously in the primordial soup. However, even the ribozymes that used these building blocks have had issues, as their inherent secondary structure is usually complicated and ordered. But even this structure would have to be made first before they could work on replicating more of themselves or RNA in general. The more complicated structures inherent in ribozymes makes it that much more difficult for replication to work.

Thus, the “structure vs replication” paradox has been a stymieing point for abiogenesis research. A replicase made out of RNA would have to form first in order to replicate more of itself, but for there to be any possibility of it forming, its structure would have to be simple. If its structure is simple, then it likely won’t be able to make more complicated replications or do replication at all. This has been a major chink in the armor of the “RNA World” hypothesis and has raised questions of if other components are needed to make it work.

Start A Little Simpler

Scientists at the MRC Laboratory of Molecular Biology in the UK decided to go back to the basics. The primordial soup itself has been shown through modeling to be capable of forming polymerized nucleotides (like NTPs) by itself without enzymatic properties being involved and that these combine into dinucleotides and trinucleotides and tetranucleotides, with each level becoming more and more rare and unlikely. Thus, the researchers wanted to see if these oligonucleotides (that is, polynucleotides made up of a very small number of nucleotides) could be used to conduct RNA replication as catalyzed by RNA itself.

Could a ribozyme be made directly by ligating together the polymerized NTP building blocks one by one, into a trio form they called triplets? If such a ribozyme was capable of ligation to make more triplets like itself, then they would be in business. Upon doing so, suddenly, this cobbled together ribozyme showed activity capable of replicating many forms of RNA, including those other kinds of impossible to copy ordered sequences mentioned previously. And this, of course, also includes being able to copy its own catalytically active domain and its own nucleotide template. In chunks, mind you, but it overall works.

These so-called emergent properties of triplet RNA synthesis seem to have a high capability to do all of the steps for replication that is needed for the eventual potential development of life. Though, with that said, we should pause for a moment and put up a clarification.

Science and Accuracy

Thus far, this is still just a proposed solution to the issue of initial RNA replication, but it does raise a new problem if it turns out to be true for how such RNA synthesis began. That original triplet ribozyme would still need to happen by itself, ligation of NTPs into triplets and all. And, while it seems far more likely than the more complicated structures used before, it’s still a possible sticking point. Then, the next steps leading to actual cells rather than simple vesicles are also no easy feat, nor the later creation of proteins. There are dozens of steps beyond ribozyme formation to find answers to.

One of the main issues with abiogenesis research is that we often look at things from a human timescale. When, in all likelihood, the chemical and enzymatic (or non-enzymatic) processes used by that original self-replicating life may have taken thousands or millions of years to build up to the eventual ribozyme and beyond. There may be methods that we aren’t aware of because each step takes hundreds of years to happen without enzymes existing to speed up the process.

Or it may be that the scientists working in this field are spot on and correct. It’s one of those things that we may never be able to know with perfect certainty, though that’s true for a lot of science and the scientific endeavor. If we can however clear up all the questions and steps in abiogenesis, we can at least say with confidence that we have found one way of creating life. And that would most definitely be an achievement.

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Photo CCs: MicroRNA and mRNA visualization in differentiating C1C12 cells from Wikimedia Commons

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