http://people.csail.mit.edu/jaffer/GTOL/nucleotide
	Evolution in the Nucleotide Game

Being easy to naturally replicate has its limits. What other strategies can enhance the survivability of a viroid?

• mechanically assisting replication
• scavenging nucleotides
• synthesis of nucleotides
• predation, stealing nucleotides from other viroids
• virocide, damaging other viroids' ability to replicate
• defending against predation and virocide
• protecting against transient environmental change (eg. drying)

The first five of these strategies are active, and will involve catalysis, reactions mediated by genetically constructed molecules. In the posited environment where genetic molecules naturally replicate, a catalyst mechanically assisting replication is not necessarily the first to evolve.

Because the organization of genetic material must predate programmed construction of non-genetic molecules, genetic material must be capable of forming a ribozyme, a genetic molecule that itself catalyzes a chemical reaction. PLoS Biology: The Ol' Switcheroo Shows How an RNA Enzyme Splices Itself describes such a molecule [13].

In order to be replicated, a genetic molecule must not be so reactive that non-nucleotides are immediately bound and block nucleotides from forming a replica or complement. A ribozyme conformation of a genetic molecule is unlikely to replicate well; and almost certainly can't participate in its own replication.

Thus there is a strong pressure for viroids to evolve into dual-strand forms. When the strands separate, the "original" strand stays in replicable form while the complement strand folds into a ribozyme to perform one or more of the functions listed above. In a dual strand viroid, some of the complement strands can be sacrificed; but some must be replicated to complete the dual-strand forms.

If the original and complement strands can both fold into non-replicable shapes, then many viroids will fail to replicate. And of those which do replicate, some of the original-sense replicates will be wasted. The efficiency of the replication process improves when original strands behave differently from complements.

In earthly life the original strands being DNA while the working complements are RNA can be seen as an example of this principle.

Some of the active functions may be impossible to accomplish with genetic material alone. By rule 10 of the nucleotide game there are non-genetic molecules which geneitc material interacts with. Because the active complement strands can be sacrificed, reactions between genetic and non-genetic molecules need not be reversible.

These helper molecules would not generally replicate with the viroid's genetic material; so a useful bond resulting from a random event would not propagate. The viroids would evolve to have configurations which would favor capture of the non-nucleotides.

Non-genetic molecules can be incorporated to the extent that genetic material can create a favorable binding site. These molecules may impart certain chemical properties to the ribozyme; or they may change the conformation of the ribozyme, altering its behavior depending on the presence or absence of molecular species.

In earth biology there are short transfer RNAs which bind to individual amino acids. Those nucleotide sequences could integrate amino acids into a ribozyme. There are also RNA sequences which bind to metal ions.

In many environments, "protecting against transient environmental change" is a crucial strategy for enhancing survivability. In all environments the initial viroids will be just nucleotides; and predation will develop. The strategies for protecting genetic material are:

• Make genetic material more tolerant of harsh conditions.
• Enclose the chromosome in non-genetic material.

Some of the nucleotides may be less stressed by an environmental condition or less susceptible to predation than others. This can select for genetic material having more of the rugged nucleotides. This can also select for a set of nucleotides different from the archaic genetic material, but which can be replicated as archaic genetic material.

But a single molecule is limited in its direct protective ability. If it devotes its entire extent to binding non-genetic molecules, then it is prevented from incorporating other genetic material and engaging in other survival strategies.

Being the same material as the chromosome, a protective capsule composed of nucleotides offers little protection. And with so many copies of the chromosome used for shielding, the yield of complete viruses would be very low. A self-assembling capsid of chromosomes binding large non-genetic molecules is more practical.

All that is lacking for this chromosome and its capsid to be a virus is for its capsid molecules to be synthesized from genetic directions, rather than being an augmented copy of the chromosome.

Protein synthesis constructs non-genetic molecules much more efficiently than embedding the molecules in genetic material. And ribosomal-RNA can create many copies of proteins from a single strand of RNA. Clearly, synthesis brings significant advantages.

Of the structures and functions which can benefit a viroid, the capsid (protection) is the one for which genetic material is least suited. Other than being self-assembling and not being made of nucleotides, capsid molecules are not strongly constrained. They should require only a few distinct molecular components. Thus the first viral ribosomal-RNAs will be much simpler than current ribosomal-RNAs; synthesizing molecules composed of only a few different types of non-genetic monomers.

Over these two chapters we have seen how the nucleotide game leads to viroids, dual-strand viruses, and even inklings of (protein) translation. The rudiments of genetic control of behavior are present even at this early stage of evolution.

We are accustomed to thinking of viruses as parasites. But at this stage of evolution, viroids and viruses are not parasites; they are the primary evolutionary actors. The culmination of the nucleotide game is Big Game Theory -- Evolutionary Breakthroughs.