The researchers, led by Howard Hughes Medical Institute investigator Jack W. Szostak, published their findings in the September 3, 2004, issue of the journal Science. Szostak and first author Irene Chen, both from Massachusetts General Hospital and Harvard Medical School, collaborated on the studies with Richard Roberts of the California Institute of Technology.
Cells are basically sacs encapsulated by bilayered membranes of fatty acids and other lipids, plus proteins. A central question in evolution is how simple versions of these cells, or vesicles, first arose and began the competitive process that drove the evolution of life.
“Most of the previous thinking about how cells grew and evolved was based on the idea of the initial evolution of structural RNAs or ribozymes — enzymes that could synthesize membrane molecules,” said Szostak. The ribozymes might have made more membrane material while the structural RNAs might have formed a cytoskeleton that influenced stability, shape, growth or division, he said.
However, Szostak and his colleagues theorized that a far simpler physical process might explain why cells would compete with one another for the materials necessary to expand their size.
“We proposed that the genetic material could drive the growth of cells just by virtue of being there,” he said. “As the RNA exerts an osmotic pressure on the inside of these little membrane vesicles, this internal pressure puts a tension on the membrane, which tries to expand. We proposed that it could do so through the spontaneous transfer of material from other vesicles nearby that have less internal pressure because they have less genetic material inside.”
In order to test their theory, the researchers first constructed simple model “protocells,” in which they filled fatty-acid vesicles with either a sucrose solution or the same solvent without sucrose. The sucrose solution created a greater osmotic pressure inside the vesicles than the solvent alone. The membranes of the simple vesicles were not as sophisticated as the membranes of today’s living cells, said Szostak. However, they closely resembled the kinds of primordial vesicles that might have existed at the beginning of evolution.
When the scientists mixed the two vesicles, they observed that the ones with sucrose – in which there was greater membrane tension – did, indeed, grow by drawing membrane material from those without sucrose.
“Once we had some understanding that this process worked, we moved on to more interesting versions, in which we loaded the vesicles with genetic molecules,” said Szostak. The researchers conducted the same competition tests using vesicles loaded with the basic molecular building blocks of genetic material, called nucleotides. Next, they used RNA segments, and finally a large, natural RNA molecule. In all cases, they saw that the vesicles swollen with genetic material grew, while those with no genetic material shrank.
It is important to note, said Szostak, the concentrations of genetic material that his group used were comparable to those found in living cells.
“In contrast to the earlier idea that Darwinian competition at the cellular level had to wait until the evolution of lipid-synthesizing ribozymes or structural RNAs, our results show that all you would need is to have the RNA replicating,” said Szostak. “The cells that had RNA that replicated better — and ended up with more RNA inside — would grow faster. So, there is a direct coupling between how well the RNA replicates and how quickly the cell can grow. It’s just based on a physical principle and would emerge spontaneously,” he said.
According to Szostak, the next step in the research will depend on another major effort under way in his laboratory to create artificial, replicating RNA molecules.
“If we can get self-replicating RNAs, then we can put them into these simple membrane compartments and hope to actually see this competitive process of growth that we are hypothesizing,” he said.
This work may help to get scientists to consider the origins of genetic coding in the first place. In actual organisms codes (such as language, the shape/charge basis of the immunoglobin system, animal calls, animal color coding (such as those used by dangerous animals to call attention to themselves), possibly olfactory codes, etc.) there is usually a prior physical sign (or many) that motivate the rise of the code. Biochemical side- and waste products are useful marks of successful processing, and can be the basis of coding strategies.
The genetic code is too sophisticated to have arisen de novo in a chemical contextual vacuum. Therefore it must have evolved. Years ago it was shown that the amino acid side chain’s solubility properties are not randomly assorted through the genetic code, but patterned. The pattern may not be so obvious in the usually depicted textbook representation of the code, but can be seen much more readily in a permutation of it, with four distinct axes which denote shape, size, charge, and solubility. Not only evolved, then, but optimized (for current chemical conditions).
The nucleotide sequence itself has physical consequences with regard to the local "melting" temperature, degree of tension, and so on- such effects would bear on how a primordial membrane-enveloped RNA would interact with its "host". Other interactions with putative proteinoid and saccharide chains would also be largely physical/mechanical at this stage of the game, with finer classical genetic coding evolving only after these subsystems had a very long time to "learn" how to manipulate each other for their own benefit, where "learning" is defined as a memory consisting of relatively long lasting alteration of a prior mix of different sequences of polymers.
Each type of code is specialized to deal with different aspects of contextually salient reality- for instance there is in eukaryotes a controversial "sugar code" theory (by a respected chemist), where branched sugar polymers encode spatial "address" information within and between cells- the polymers are almost ubiquitously attached to membrane elements, soluble proteins, and so on. The sugars themselves are attached incrementally in hierarchical fashion to the growing polymer, and appear to encode finer and finer detail features the further out from the base they are. This code, by the way, is also involved in immunity.
Evolved biomacromolecules complexify to incorporate all sorts of switches and toggles for regulatory purposes which lead to much greater processual integration. If one extrapolates backwards one ends up in a state where there is very little of this going on, and then we are left with either randomly organized or uniform polymers kinda just staring at each other, interacting in the grossest possible (physicomechanical) fashion.
Codemaniac
VERY interesting. Excellent job of organizing and expressing complicated thoughts in a straightforward manner. I enjoyed reading this and keep our site going here just for comments like this one to get posted. You REALLY, REALLY want to start writing for SciScoop regularly, right?
“This work may help to get scientists to consider the origins of genetic coding in the first place.”
Considering that the fat-slurping effect occurs with just sucrose and no RNA, it seems doubtful that the tertiary structure of RNA (determined by its sequence) has any relevance.
It’s my guess that if the pre-protein/DNA regime has had any lasting influence on RNA sequence, it is found in the non-coding regions of RNA: introns, rRNA, tRNA, the RNA component of RNase P, etc.