prebio

Prev: Prebiotic evolution (overview) Next: Quasispecies theory


 * Todo List**
 * REF vesicles
 * REF catalysis
 * REF replicators
 * Improve explanation of catalysis-first scenario

=Prebiotic evolution: Evolution of entities before complex cellular life=

One of the most fundamental issues in biology is the question of the [|origin of life]: How did life arise from molecules in the environment of a pre-biotic world? Not surprisingly there are many hypotheses and theories about this issue. Some of the main ones we will address here.

So far research has perhaps mainly focussed on three major aspects of life:
 * [|vesicles]: how do vesicles emerge from the properties of lipids and how do they grow and divide? (REF)
 * **[|catalysis]**: how do we get [|self-sustaining networks of catalytic peptides] (as we see in cells)? (REF)
 * **[|replicators]**: how do we get replication of [|information]-coding molecules (as we see in [|RNA] and [|DNA])? (REF)

In each case there is a focus on building blocks (i.e. a basic unit from which complexity can be assembled) and some form of replication process. Assuming the availability of these simple building blocks, we can summarize these theories as:


 * || **Replication*****-first** || **Catalysis-first** || **Compartments-first** ||
 * **Building blocks** || RNA || peptides and/or RNA || lipid vesicles ||
 * **Amplification** || evolutionary optimization || auto-catalytic networks || growth / division ||
 * **In vitro** || ribozyme selection || peptide libraries || protocell (+ replication) ||
 * Evolutionary optimization is Darwinian selection: replication followed by mutation and selection.

These scenarios basically give a different answer to the question: What is the most basic feature of life?

//1. Life is... energy/nutrient cycling (Catalysis-first)//
All living organisms have catalytic networks that convert certain nutrients into building blocks or energy. Furthermore, the core machinery in these networks seems to be conserved over many species. We could therefore speculate that (auto)catalytic networks stood at the basis of life. In this scenario, there has been a focus on [|hydrothermal vents], where we get energy (temperature) gradients and compartments (in the rock) for free, and in this rock there are potential catalytic substances (metal sulphides). This would create an optimal environment for the arisal of autocatalytic sets (of e.g. peptides). However, the main question in this scenario remains: are these autocatalytic sets evolvable?

//2. Life is... cells (Compartments-first) //
As suggested by e.g. Szostak ([|2011]), life requires compartmentalization ([|protocells]). These compartments ensure some kind of organisation, and furthermore allow for competition between different compartments (and hence selection). In wetlab experiments, Szostak et al. have shown that they can get large, heterogeneous, mutlilamellar vesicles (i.e. micells/protocells with fatty acid "membranes") that grow and divide into multiple daughter cells. Furthermore, these protocells can absorb fatty acids from other protocells, leading to competitive growth (Adamala and Szostak [|2013]). One interesting point from Szostak's experiments is the following: Initially, they worked in a very "clean" system, studying uniform, unilamellar vesicles. This led to problems with divisions: during each division the volume decreased until eventually the vesicles were to small and disappeared. When they switched to more heterogenenous, multilamellar vesicles, these problems disappeared and they found protocells that can keep dividing without volume loss. Actually, this heterogeneity is more likely to occur in a highly heterogeneous, "messy" environment, which is what we should expect from e.g. a "prebiotic soup". This example shows that, while in experiments we always try to be as "clean" as possible, the heterogeneity that we should expect from the real life might sometimes make things easier!

//3. Life is... evolution (Replication-first)//
We can also state that the main characteristic of life is replication of "heritable" information that can be selected. According to Gerald Joyce ([|2012]), living systems: From this starting point, RNA is a good candidate molecule because RNA can both store information (template, nucleotide sequence) and catalyze reactions such as its own replication (i.e. [|ribozymes]).
 * have a molecular memory (genotype)
 * which is shaped by experience (selection)[[image:RNA_invitro_evolution.png align="right"]]
 * and maintained by self-replication.

The current in vitro "state of the art" of an RNA system that is capable of ongoing Darwinian evolution is (Lincoln and Joyce [|2009]):
 * an evolving and self-replicating system,
 * that is ligation based: A + B + E -> E.AB -> E.E -> E + E.
 * This system grows exponentially and evolves.
 * However: only a few nucleotides are prone to evolution, most nucleotides in A and B are fixed. These fixed nucleotides are "borrowed" from a current ribozyme, that is known to have a ligation function.

//RNA world//
We will focus on the latter situation, with RNAs as replicators as well as information carrying molecules. Our focus is then whether RNA molecules, with some form of self-organization, could achieve something which goes some way towards living systems. Recent findings indeed show that many RNAs can act as enzymes. In this way we have molecules which have some special properties and behaviour and are capable of carrying the information coding for these properties, and replicating it.

In our approach to the origin of life we focus first on replicators in the form of RNA molecules. Unlike peptides, in which self-replication is always highly dependent on particular other peptides (non-generic), RNAs in principle can always self-replicate. In this way an RNA-world provides the minimal requirements for evolutionary optimization (Darwinian selection):
 * generic replicators
 * independent synthesis and decay[[image:http://universe-review.ca/I11-21-tRNA1.jpg width="222" height="258" align="right"]]
 * mutation
 * competition

Since a decade ago we can evolve 'ribozymes' (RNAs with enzymatic function) giving impetus to the idea of a prebiotic RNA world. The difficult problem is the synthesis and stability of RNA and one of the biggest questions in prebiotic evolution is how early RNA replicators managed to evolve into larger complexes.

Given that an RNA world would suffice in terms of the minimal requirements for evolutionary optimization, the most immediate question is therefore whether Darwinian selection would actually occur, and what would be its consequences. This issue was studied by Eigen et al. (1971, 1989) when they developed their quasispecies theory.

Next: Quasispecies theory