Pandora's box is viral

Anyone who reads my blog regularly will know my fondness of viruses (they feature in most posts). I am particularly curious about giant viruses and have previously posted about these (link one and two). The giant virus field has recently grown larger (pun completely intended) with the addition of a new family of even larger viruses, so I thought it was about time to update the story.

Pandoravirus

The recently discovered viruses are known as Pandoraviruses and are not just causing excitement because of their size. But let's start with their size. A conventional microscope cannot see the majority of viruses, unlike bacteria and eukaryotic cells (such as our own). Their size is usually in a range of 50-150 nanometers (influenza virus for example is about 100 nanometers in diameter). A nanometer is millionth of a millimeter - the average pinhead has a diameter of 2 millimeters, meaning the average virus is around 20,000 times small than a pinhead. Another comparison would be to bacteria, which are usually around 1000 nanometers in length. Pandoraviruses are not like most viruses; they stands at a whopping 1000 nanometers long and about 500 nanometers across – dwarfing nearly all other viruses and even some bacteria. They don't even look like viruses! It's quite possible these viruses were discovered 13 years ago, but were not appreciated for what they truly are.

Know your sizes

 As if the sheer physical size wasn't enough, let's consider the genome size. We humans have a genome of around 3 billion bases (a base being the individual unit of DNA), which encode between 20,000 and 30,000 genes. Bringing things down to the virus scale, HIV-1 has a genome made of around 10,000 bases, which code for 9 genes. Influenza is slightly larger, having a genome of around 14,000 bases, coding for 11 genes. Viruses are traditionally known for being small and not carrying much luggage in their genetic material. In stark contrast, Pandoraviruses have up to a staggering 2.5 million bases, coding a total of 2556 genes. This is more genetic material than a lot of bacteria and even some parasitic eukaryotic organisms.

Comparison of genome sizes for different domains of life (and viruses)

Size matters, but that is by no means the most interesting thing about Pandoraviruses. All life on Earth is classified into three domains on the so-called tree of life: eukaryotes, bacteria and archaea. When the genes and proteins of all these different domains are compared there are strong similarities. Eukaryotes tend to have the most complexity, but at the core, certain things are the same. For instance, imagine a protein that has a structure of AABCDD in a bacterium. This may be the simplest form of that protein. We humans may have a very similar core structure but have, through evolution, made it more complex – for example, AAA*BCD*D*EEFG (where the * is denoting small changes to that unit). While this is different it still carries strong similarities to the simpler, bacterial protein. These similarities point towards the fact that all life on Earth may have originated from a single point – the seed for the tree of life – which has then branched out through evolution to give all the life we see around us.

Basic diagram of the three domains of life

Viruses are not considered living; so do not fit onto the tree of life. However, they do adhere to the rule of thumb of having strong similarities to other organisms. While not living, they are still similar to the living. Again, that is the story for most viruses, but not the Pandoraviruses. Only 7% of the Pandoravirus genome has similarity to our existing database of proteins and genes. This means 93% of the proteins Pandoviruses produce have no similarity to anything we have knowledge about…

This complete lack of similarity to any other form of life raises something potentially very fundamental about our view of the world. There is a view that these giant viruses evolved in a reductionist manner. Evolution is often thought of in a unidirectional manner, gaining increased complexity. However, this is not a rule of evolution, the rule of evolution is the selection of advantageous traits. If becoming less complex provides an advantage then this will be selected for. The hypothesis surrounding the giant viruses is that they were once free-living cells (similar to a bacterium for example) that through evolution lost their self-sufficiency, instead becoming dependent on a host to reproduce - a trait of a virus. If this were the case then giant viruses would need to be related to other forms of life, since would have originally been a life form unto themselves. However, as I've said, there is only 7% similarity between Pandoraviruses and all other life forms. This means that the ancestors of Pandoraviruses were probably very different to the ancestors of bacteria, archaea and eukaryotes. Therefore, where do they fit in our view of evolution? One resolution of this issue is that maybe there aren't (or at least weren't) only three domains of life. Pandoraviruses and the other giant viruses could represent the modern day descendants of a forth domain of life. This is merely an idea with no real concrete evidence, but it seems exciting to me that as we learn more about these giant viruses, and as we discover more (which I'm sure we will), our view of life on Earth may need to change. As has often been the case in biological science, viruses could be paving the way to a huge shift in our understanding of the world around us.