I read the article by DeRoos with interest. However, it is not clear to me how dsRNA could preceed ssRNA. If dsRNA is the precursor to ssRNAs with some activities or phenotypes, how would the dsRNA arise in the first place? The hybridization model presented in Figure 2 presupposes the existence of ssRNA oligomers. This seems counterintuitive ... or am I missing some key point?
Competing interests
none
Re: Running before walking
Albert de Roos, Syncyte BioIntelligence
20 June 2007
In reply to the comment of Niles Lehman, it is true that I do assume single-stranded oligonucleotides to be available and where I write that single stranded RNA (ssRNA) preceded double-stranded RNA, I mean ssRNA as the carrier of catalytic function.
I also notice that my perception of OOL research is different from that of the mainstream scientists in the field, as also indicated by the reviewers of the manuscript and would like to expand a little on it. I do assume the presence of ribonucleotides as the building blocks of life, but recognize that this is indeed not trivial and I do not deny that there seem important chemical hurdles to take for an abiotic generation of oligo-ribonucleotides (or its precursors). However, ribonucleotides are the actual building blocks of Life as we know it, and we also know that there was a point in the evolution of life where the genome found a way of creating enzymes that would specifically make those building blocks of Life. But even though ribonucleotides are a prerequisite for Life, they do not constitute Life and even if we had plenty of ribonucleotides available, it will not advance our knowledge of the origin of life. Instead, we have to study the assembly of the molecular machine that constitutes Life, not its building blocks in order to understand it.
In my opinion, Life and its evolution should be seen as a molecular machine that can be described by a model, in this case an engineering design. In such a model, ribonucleotides are a precondition but the abiotic generation of these building blocks are not part of the system. Like the tools that are used to assemble a car, or the gasoline that provides the energy, they are needed but not part of the system nor describe the system. Of course it will be a problem for the OOL hypotheses if we can’t make those building blocks abiotically, but will it affect the origin of our Life? Other sources for the building blocks may then be necessary, which could be extraterrestrial, or the product of an unknown life form or abiotic autocatalytic cycles (I prefer the latter). For the moment, without a scenario for the origin of Life, it seems preliminary to conclude that the generation of ribonucleotides is the main aspect for OOL research. For me, it is like focusing on the production of gasoline as a fuel for a car, when in fact we are dealing with a diesel engine. Similarly, I also do not need to explain how the crude oil was formed or how the refinery process for the fuel works in order to understand the engine.
Where does the origin of Life as a system exactly starts? First of all, it depends on the scenario that was followed. A scenario in which a self-replicating ribozyme evolves first, will point to a different mechanistic origin than a scenario in which an abiotic replication system based on double-stranded RNA arose first (as in my article). In any case, the origin of life should be defined at the system level (not at the molecular building block level) and it originates when a self-contained and evolving system arises that contains the information to build Life. It is when the dependencies on other systems are reduced, when the information to copy the genome is in the genome itself, i.e. when a self-contained system has evolved. This would include a genome-encoded replicator, but also the enzymes that catalyze the formation of the building blocks. In my model, double-stranded RNA could provide the starting point, because it can work as an abiotic template for the generation of catalytic molecules.
It should also be realized that there is no theoretical basis for a self-replicating ribozyme that evolved into the biomolecular machine that has double-stranded DNA as the informational carrier and single-stranded RNA as the carrier of the catalytic function (i.e. Life as we know it, not some putative life form). Although RNA with replicase activity has been created in the laboratory, we have no evidence that such a ribozyme ever existed and the steps to a genome based on such a replicase are completely unknown. In my opinion, these studies belong to the field of Artificial Life because it has no relationship with the system of Life as we know it. But for ALife research, this ‘forward engineering’ is a very strange approach because no one has ever produced a machine that even remotely resembles Life or evolution. So mainstream OOL research is focused on efforts in recreating putative building blocks while having no idea what the next step would be, and having no framework nor a concrete scenario to work with. It is like starting to weld some metal together without a plan of how these ever can be assembled into a car while maintaining that the art of welding is the clue.
What we have to do is reverse engineering Life, meaning that we have to carefully look what it does, how it works and how it could have been assembled in evolution. That’s the work of engineers and they will recognize that such a complex system needs a design (without religious or atheist connotations). Apart from the mechanistic implementation, one could determine the requirements like flexibility and robustness of such a system, and deduce possible basic architectures. Designs allowing for evolvable systems have been developed in the recent years, driven by the ever-increasing complexity of software. In my opinion, the solution to the origin of life will come from the merger of system design with molecular evolution. This means that we have to recruit more people from the ALife and complex system design into the OOL field and educate them in the technical (biomolecular) implementation so that we can reverse engineer Life.
Competing interests
None
Mechanism for thermal cycling in the RNA world
Rowena Ball, ANU
24 April 2015
Pleased to see that de Roos recognised in 2007 the necessity for thermal cycling to drive replication in the non- or proto-cellular RNA world. It is now accepted that primordial non-cellular RNA communities must have been subject to a periodic drive in order to replicate and prosper. We proposed and tested a natural mechanism for such a drive in three papers:
R. Ball and J. Brindley. Hydrogen peroxide thermochemical oscillator as driver for primordial RNA replication. J. Roy. Soc. Interface 11, 20131052, 8 pages, 2014. (doi: 10.1098/rsif.2013.1052).
R. Ball and J. Brindley. The life story of hydrogen peroxide I. A periodic pH and thermochemical drive for the RNA world. J. Roy. Soc. Interface, 2015 - to appear.
R. Ball and J. Brindley. Thiosulfate-hydrogen peroxide redox oscillator as pH driver for ribozyme activity in the RNA world. Origins of Life and Evolution of Biospheres, 2015 - to appear.
Running before walking?
18 June 2007
I read the article by DeRoos with interest. However, it is not clear to me how dsRNA could preceed ssRNA. If dsRNA is the precursor to ssRNAs with some activities or phenotypes, how would the dsRNA arise in the first place? The hybridization model presented in Figure 2 presupposes the existence of ssRNA oligomers. This seems counterintuitive ... or am I missing some key point?
Competing interests
none
Re: Running before walking
20 June 2007
In reply to the comment of Niles Lehman, it is true that I do assume single-stranded oligonucleotides to be available and where I write that single stranded RNA (ssRNA) preceded double-stranded RNA, I mean ssRNA as the carrier of catalytic function.
I also notice that my perception of OOL research is different from that of the mainstream scientists in the field, as also indicated by the reviewers of the manuscript and would like to expand a little on it. I do assume the presence of ribonucleotides as the building blocks of life, but recognize that this is indeed not trivial and I do not deny that there seem important chemical hurdles to take for an abiotic generation of oligo-ribonucleotides (or its precursors). However, ribonucleotides are the actual building blocks of Life as we know it, and we also know that there was a point in the evolution of life where the genome found a way of creating enzymes that would specifically make those building blocks of Life. But even though ribonucleotides are a prerequisite for Life, they do not constitute Life and even if we had plenty of ribonucleotides available, it will not advance our knowledge of the origin of life. Instead, we have to study the assembly of the molecular machine that constitutes Life, not its building blocks in order to understand it.
In my opinion, Life and its evolution should be seen as a molecular machine that can be described by a model, in this case an engineering design. In such a model, ribonucleotides are a precondition but the abiotic generation of these building blocks are not part of the system. Like the tools that are used to assemble a car, or the gasoline that provides the energy, they are needed but not part of the system nor describe the system. Of course it will be a problem for the OOL hypotheses if we can’t make those building blocks abiotically, but will it affect the origin of our Life? Other sources for the building blocks may then be necessary, which could be extraterrestrial, or the product of an unknown life form or abiotic autocatalytic cycles (I prefer the latter). For the moment, without a scenario for the origin of Life, it seems preliminary to conclude that the generation of ribonucleotides is the main aspect for OOL research. For me, it is like focusing on the production of gasoline as a fuel for a car, when in fact we are dealing with a diesel engine. Similarly, I also do not need to explain how the crude oil was formed or how the refinery process for the fuel works in order to understand the engine.
Where does the origin of Life as a system exactly starts? First of all, it depends on the scenario that was followed. A scenario in which a self-replicating ribozyme evolves first, will point to a different mechanistic origin than a scenario in which an abiotic replication system based on double-stranded RNA arose first (as in my article). In any case, the origin of life should be defined at the system level (not at the molecular building block level) and it originates when a self-contained and evolving system arises that contains the information to build Life. It is when the dependencies on other systems are reduced, when the information to copy the genome is in the genome itself, i.e. when a self-contained system has evolved. This would include a genome-encoded replicator, but also the enzymes that catalyze the formation of the building blocks. In my model, double-stranded RNA could provide the starting point, because it can work as an abiotic template for the generation of catalytic molecules.
It should also be realized that there is no theoretical basis for a self-replicating ribozyme that evolved into the biomolecular machine that has double-stranded DNA as the informational carrier and single-stranded RNA as the carrier of the catalytic function (i.e. Life as we know it, not some putative life form). Although RNA with replicase activity has been created in the laboratory, we have no evidence that such a ribozyme ever existed and the steps to a genome based on such a replicase are completely unknown. In my opinion, these studies belong to the field of Artificial Life because it has no relationship with the system of Life as we know it. But for ALife research, this ‘forward engineering’ is a very strange approach because no one has ever produced a machine that even remotely resembles Life or evolution. So mainstream OOL research is focused on efforts in recreating putative building blocks while having no idea what the next step would be, and having no framework nor a concrete scenario to work with. It is like starting to weld some metal together without a plan of how these ever can be assembled into a car while maintaining that the art of welding is the clue.
What we have to do is reverse engineering Life, meaning that we have to carefully look what it does, how it works and how it could have been assembled in evolution. That’s the work of engineers and they will recognize that such a complex system needs a design (without religious or atheist connotations). Apart from the mechanistic implementation, one could determine the requirements like flexibility and robustness of such a system, and deduce possible basic architectures. Designs allowing for evolvable systems have been developed in the recent years, driven by the ever-increasing complexity of software. In my opinion, the solution to the origin of life will come from the merger of system design with molecular evolution. This means that we have to recruit more people from the ALife and complex system design into the OOL field and educate them in the technical (biomolecular) implementation so that we can reverse engineer Life.
Competing interests
None
Mechanism for thermal cycling in the RNA world
24 April 2015
Pleased to see that de Roos recognised in 2007 the necessity for thermal cycling to drive replication in the non- or proto-cellular RNA world. It is now accepted that primordial non-cellular RNA communities must have been subject to a periodic drive in order to replicate and prosper. We proposed and tested a natural mechanism for such a drive in three papers:
R. Ball and J. Brindley. Hydrogen peroxide thermochemical oscillator as driver for primordial RNA replication. J. Roy. Soc. Interface 11, 20131052, 8 pages, 2014. (doi: 10.1098/rsif.2013.1052).
R. Ball and J. Brindley. The life story of hydrogen peroxide I. A periodic pH and thermochemical drive for the RNA world. J. Roy. Soc. Interface, 2015 - to appear.
R. Ball and J. Brindley. Thiosulfate-hydrogen peroxide redox oscillator as pH driver for ribozyme activity in the RNA world. Origins of Life and Evolution of Biospheres, 2015 - to appear.
Competing interests
No competing interests.