05/04/2015 03:14 pm ET | Updated May 02, 2016

The "First Replicon" on Earth? A Chat With Virologist Ricardo Flores


I spoke recently with virologist Ricardo Flores, Research Professor of the Spanish Research Council at the Institute for Cellular and Molecular Plant Biology in Valencia, Spain. Flores thinks viruses may be "the most important faction of the [planet's] biomass" and that a viroid-like entity is a prime candidate for the first replicon on Earth. Viroids are subviral world parasites, non-protein coding RNAs. Excerpts of our interview follow.

Ricardo Flores: Studies of the ocean are now revealing a further diversity of life totally unexpected, as we have discovered that the number of viral particles there is extremely high. One cell can harbor many, many viral particles.

Viruses may be the most important faction of the biomass.

We know now that there is a subviral world, which was not realized for the first 70 years of the 20th century. . . . Viroids represent the smallest organisms in terms of size on the biological scale. Compared to the genome of the tobacco mosaic virus, the viroid genome is 20 times smaller. . . . The simplest is the oldest in evolutionary terms and viroids fit very well with this notion.

I consider a viroid-like entity actually a very good candidate for the first replicon that may have populated Earth at the beginning of life. This enthralling hypothesis was first proposed by Theodor Diener, the discoverer of viroids.

But when initial experiments on viroids were done in the 1970s, it was difficult to convince the scientific community something of that size with such peculiar properties would be able to replicate.

A viroid RNA, for instance, doesn't code for any protein. It doesn't need to go to ribosomes and instruct them to generate proteins. What a viroid needs is to go to a cell nucleus or chloroplast -- if it's a plant -- and parasitize an RNA polymerase. . . . A viroid needs to find a way to be replicated and that's it. Nothing else.

Suzan Mazur: What is life to you? How do you think about it?

Ricardo Flores: For me the key point of life is the ability to get copies in an appropriate medium, copies essentially identical to the original one.

If you consider bacteria growing in a Petri dish, you only need to add a very simple medium -- some sugars and mineral salts -- that's it. Bacteria will grow and reproduce. If you go one step down to a very simple mycoplasma. . . you need a much more complex medium. And if you go one step further down from that to a virus or viroid, you need an even more complex medium. A virus or viroid cannot replicate except within a living cell.

With bacteria, mycoplasma and virus or viroid, when the complexity of one of the components of the system increases -- the other decreases. When the bacteria is very complex, the medium can be simple. When the mycoplasma is less complex, the medium must be more complex. And when the virus or viroid is even less complex, then you need a very complex medium -- a cell.

The complexity of the whole system must be in some way preserved. If you simplify one of the components, you need to increase the complexity of the other components of the system. For life you need complexity of the whole system.

Suzan Mazur: How does a virus insert itself into a cell?

Ricardo Flores: In the case of animal viruses there are specific receptors in the membrane of the cell, which are proteins the virus manipulates to facilitate entry. In the case of plant cells, there are no receptors. Plant viruses or viroids enter the plant cell through a mechanical injury to the plant.

Viruses need to manipulate different cellular pathways. . . . Viruses reprogram the cell's ribosomes to produce the proteins they encode. Viroids need to manipulate the cell's transcriptional machinery, to sequester an RNA polymerase for their own replication.

Suzan Mazur: So viruses are alive in the sense that they can manipulate the receptors to enter the cell, etc.

Ricardo Flores: Yes, viruses can take advantage of the cell's receptors. But for me the key point is not whether they can enter the cell, it is to use the machinery of the cell to get copies of the genome of the virus (or viroid). . . .

Viruses and viroids are able to direct their own replication in the medium -- the cell -- and during the process of replicating they evolve because replication introduces mutations. Those are the two characteristics of life. To be able to replicate and get copies that occasionally are not identical to the original one. In this way viruses and viroids are able to evolve, and in this respect are similar to cells. . . .

We now know there are viruses affecting animals, bacteria, mycoplasma, any type of cells. . . .

Suzan Mazur: Viroids as we know them today are only associated with plants, aren't they?

Ricardo Flores: Yes, they are infecting only plants. . . . Despite the names viroid and virus that seem to establish a connection, there is apparently no evolutionary connection. Viroids are much simpler than viruses and are non-protein coding RNAs. . . .

The crucial thing is that at least some viroids are catalytic RNAs, and in the RNA world everything was catalyzed by RNA. . . . That is why there is quite a strong argument for a viroid-like entity having appeared in the early steps of the emergence of life.

Suzan Mazur: Do you think scientists are going to make life in the lab anytime soon? Jack Szostak announced at the 2014 World Science Festival that he thinks he'll have "life in the lab" in three years. That means in two years.

Richardo Flores: It could be. This is now more a technical problem than a basic problem.