Monday, April 09, 2012

Evolution of virus- Is it fitting right?

          I have had a good audience response for my posts on basic stuff than when i came up with research based materials. (Oh ya, ultimately everything is research based, but what i mean to say is recent research). The stats make me say that.

         So today i decided to write on a topic that many has questioned me. The question reads so "If one strategy of viral replication is very efficient, why do we have 7 basic protocols for viral replication". To make things easy, let me divide this entire discussion to 2 parts- Replication strategy and what's the advantage.

Replication strategy:

There are all combinations of genetic material in a virus. Single or double stranded DNA, Single (Plus and minus strand) or double stranded RNA . A total of 7 genetic material types are known in virus family. Refer fig below

Fig 1: Genetic materials in virus (For source click here)

         David Baltimore based on his observations concluded that all the virus has to make mRNA to effectively replicate no matter what genome is the virus made up of. The 2nd rule is Only dsDNA can transcribe (Not single) and dsRNA cannot encode protein. The 3rd rule is that the host cell don't encode RNA dependent RNA polymerase (Means the host cannot make RNA from RNA). Since the virus doesn't possess its own machinery it has to use everything from the cell, and if cell don't possess the required material then the virus has to make it. If you know the following diagram speaks for itself.

Fig 2: The Baltimore classification (Source)

Fig 3: Viral replication strategy (Click here for source). 

For people who still need more help understanding, You must listen to Microbiology Podcast TWiV 49

Now let us consider each of the genome.

            Suppose the genome is DNA based, the best advantage is the virus has a stable genome (DNA is more stable than HIV in cellular conditions). In addition it can make use of the host cell machinery in every way cause the cell itself has DNA. Which means, the virus actually needs to code less (In reality Some DNA virus are really large such as Herpes virus). Alas, but it has to take over the problem of entering the nucleus. And this represents the problem. That is, the nucleus is not permissive to incoming genomes and hence the virus will have to evolve special strategies to enter the nucleus and take charge. So i can conclude safely that here the evolutionary fitness is towards a very stable genetic material- "DNA".

           Consider the second case, a + sense RNA. RNA is not stable material in cytoplasm because of various factors such as half life and various attacking enzymes. But, this low time availability is compromised by the fact that the + sense mRNA is able to make proteins directly and get out quickly. Though we (We means Science here) don't know what's the function of - sense mRNA that will be produced as intermediate to make more + sense RNA i often felt it serves as a decoy. That means the virus is fast, avoids the problem of entering the nucleus and hence codes only for whatever is essential for itself- a cover and a RNA making machinery. This means it can afford really small genome. In this case the fitness is towards feasibility and not stability.

          Now let's consider the 3rd case, a - sense RNA. This is bit of a trick, as the -sense RNA doesn't make anything. So it has to carry a RNA synthesizing machinery with it and the rest is as for the + sense RNA. Probably, here the -sense RNA is the decoy. The next is a combination of + and - RNA to make a double stranded RNA. This avoids the problem of stability as double stranded RNA is more stable. Oh yeah!! We eukaryotes know how to cleave dsRNA in cytoplasm (refer RNA interference). So in case of  RNA machinery no matter which type, the evolutionary preference to maintain is because of easiness of replication than the stability.

          Retrovirus has the elegance of both worlds. Have an RNA and make a DNA. This means the that the RNA is the material but converted to more stable DNA once inside the cell. HIV for e.g is a +sense RNA virus but instead of taking the routine route, it decides to go to nucleus and integrate. At the cost of what? Yes, at the cost of having to have a strategy to enter the nucleus. But, i would say still this system is best compared to others. Because once inside the nucleus the cell does everything for the virus and the virus just has to control. Which means least genetic material can be carried.

         One would argue with me easily that this is just blunder. If retrovirus is so good, then this group of virus should have predominated the viral population, which is not the case. Well, that were HERV comes to picture (refer my previous post on HERV). Infact almost every eukaryote has a ERV genome sitting inside its own genome replicating at the cost of host. You may say that its not active, but that doesn't matter. Ultimately the viral genome can parasitize successfully.

          So, my impression to the question is all the viral replication strategy has evolved either because, its genome is more stable or replication is more feasible. The one which combines the best of both is retrovirus and it is infact evolutionarily the fittest.

This doesn't break any rules, does it?

Further reading

1. Classification of virus, link

2. Introduction to molecular virology, link

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