# Cooperation, enzymes, and the origin of life

Enzymes play an essential role in life. Without them, the translation of genetic material into proteins — the building blocks of all phenotypic traits — would be impossible. That fact, however, poses a problem for anyone trying to understand how life appeared in the hot, chaotic, bustling molecular “soup” from which it sparked into existence some 4 billion years ago.

Throw a handful of self-replicating organic molecules into a glass of warm water, then shake it well. In this thoroughly mixed medium, molecules that help other molecules replicate faster –- i.e. enzymes or analogues thereof — do so at their own expense and, by virtue of natural selection, must sooner or later go extinct. But now suppose that little pockets or “vesicles” form inside the glass by some abiotic process, encapsulating the molecules into isolated groups. Suppose further that, once these vesicles reach a certain size, they can split and give birth to “children” vesicles — again, by some purely physical, abiotic process. What you now have is a recipe for group selection potentially favorable to the persistence of catalytic molecules. While less fit individually, catalysts favor the group to which they belong.

This gives rise to a conflict opposing (1) within-group selection against “altruistic” traits and (2) between-group selection for such traits. In other words, enzymes and abiotic vesicles make an evolutionary game theory favourite — a social dilemma.

As it turns out, abiotic vesicles may have existed at the dawn of life. Carbonaceous meteorites have been found to contain amphiphilic molecules, whose ability to bind to both water and fatty compounds allow them to create vesicle-like boundaries (incidentally, this is the same mechanism that allows soap to capture dirt inside amphiphilic rings). Furthermore, these vesicles can divide or “reproduce” under shear stress or photochemical stimulation. Because of these cell-like properties, many scientists believe amphiphilic structures may have a played a crucial role in abiogenesis:

As Artem highlighted before, these primitive cell-like vesicles can be produced in the laboratory. From Thomas M.S. Chang’s early work at McGill to the current efforts of Albert Libchaber’s group working on creating artificial cells — the results so far are promising. For example, Libchaber managed to create persistent self-organizing lipid bilayers (also made up of amphiphilic molecules) which could be induced into replication through fission. This breakthrough supports the idea that protocells can emerge abiotically, with one major caveat: for these lipid bilayers to properly grow, their environment has to be chemically controlled to balance the volumetric growth caused by water absorption and the expansion of the cell surface enabled by the attachment of fatty acids drawn from the environment.

This caveat aside, let us suppose that amphiphilic protocells containing self-replicating molecules did exist at the dawn of life. How, then, could enzymes have evolved? Under what conditions could between-group selection have outweighed molecular “selfishness”?

This is the question that Bianconi et al. (2013) have attempted to answer by building a simple model in which self-replicating, RNA-like molecules are encapsulated inside vesicles or “protocells”. They considered two types of molecules: A type molecules are catalysts, also called replicases, which facilitate the self-replication of other molecules, while B type molecules are non-catalysts. A molecules can turn into B molecules if a mutation affects the nucleotide strand(s) responsible for the catalytic function, with probability (1 – q). Where q is the probability that an A type molecule remains of the A type, and is defined as $q = (1-u)^L$ where u is the point mutation rate and L is the length of the nucleotide sequence (number of nucleotides) that code for the catalytic function.

Reverse mutations from B to A are considered negligible because a specific sequence is needed to encode catalysis, and are therefore excluded from the model.

Not all catalysts act in precisely the same way, and the basic set up is summarized above. Bianconi et al. (2013) defined four types of replicases: $R_1$, $R)2$, $R_{1,\alpha}$ and $R_{2,\alpha}$. $R_1$ and $R_{1,\alpha}$ replicases help other molecules replicate including themselves, whereas $R_2$ and $R_{2,\alpha}$ replicases never help. In protocells containing $R_{1,\alpha}$ or $R_{2,\alpha}$ replicases, the replication rate is incremented by a constant amount $\alpha$ with each additional replicase; whereas for $R_1$ and $R_2$ replicases, the replication speed is the same whether one or several replicases are present (replication rate is a > 1).

In the model, vesicles split once they reach a determined number of contained molecules. Two types of vesicle division were considered: division into two, where the contained molecules are split at random between two children vesicles, and division into many, where each molecule segregates into its own vesicle.

Bianconi et al. (2013) ran the model for different replicases, division size thresholds and types of division (into two vs. many). Each type of replicase can persist if q, the probability that an A molecule remains of the A type at each iteration, and the increase in replication rate (a for $R_1$ and $R_2$, $\alpha$ for $R_{1,\alpha}$ and $R_{2,\alpha}$), are high enough. A threshold value $q_c$ is found at different values of $a/\alpha$, above which replicases can persist, and below which replicases go extinct. The results are summarized in the following graphs:

The authors derive four main observations from the simulation:

1. As could be expected, the evolution of altruistic replicases ($R_1$ and $R_{1,\alpha}$) is harder than the evolution of commensal replicases ($R_2$ and $R_{2,\alpha}$).
2. For a given division threshold m, division into two makes enzymatic activity easier to evolve: selection for replicases can accommodate higher mutation rates.
3. Larger cells favor the evolution of replicase activity most of the time (greater m leads to lower $q_c$).
4. All else being equal, additive enhancement of replication rate ($R_{1,\alpha}$ and $R_{2,\alpha}$) is more favorable to replicase activity than fixed-rate enhancement ($R_1$ and $R_2$).

Because the model is not parameterized according to quantified observations, it cannot be used to assess the precise conditions under which enzymes could have evolved. But it confirms that group selection can in theory give rise to enzymatic activity and it provides a general description of the ideal environment for such activity.

Bianconi, G., Zhao, K., Chen, I.A., & Nowak, M.A. (2013). Selection for replicases in protocells. PLoS Computational Biology, 9 (5) PMID: 23671413

### 8 Responses to Cooperation, enzymes, and the origin of life

Dear Colleague,
I am sending you the information. Have a look at it please.
Sincerely,
Professor of Physical Chemistry

Origin of life and biological evolution .
Molecules – “blocks of life” (nucleobases, amino acids, sugars, phosphates and other compounds) are produced as a result of chemical evolution in appropriate conditions in the various parts of the universe. These molecules are initial components in the synthesis of nucleic acids (DNA and RNA), proteins, biopolymers and other metabolites. Thermodynamic “principle of substance stability” is the driving force behind the selection of the most stable supramolecular structures in the presence of water. Thermodynamics provides a common genetic code in the universe. Thermodynamics directs the chemical and the prebiotic evolution. And then begins the Darwin’s evolution. It (as well as the prebiotic evolution) is governed by the laws of hierarchical thermodynamics and the principle of substance stability. Generalized Gibbs equation at quasi-approximation can be applied to all hierarchical levels of living matter.

Int. J. Mol. Sci. 2006, 7, 98-110 http://www.mdpi.org/ijms/papers/i7030098.pdf

Thank you.