Sunday, October 16, 2011

The world's largest virus

Back in January I blogged about how the physical constraint of capsid size may be forcing some viruses to squeeze their genomes into such a compact state that their genes overlap. Now we visit the other end of the scale to the largest virus yet discovered, appropriately called Megavirus chilensis, found in ocean waters off the coast of Chile.

As one of the paper's coauthors told BBC News, "You don't need an electron microscope to see it; you can see it with an ordinary light microscope." Each virus particle is about 680 nm across, or just under a micrometer, making it just barely visible as specks by light microscopy. They're structurally interesting, bearing a covering of fibers ("hair") all over the surface, and a five-pronged star-shaped structure on one vertex that the authors have called a "stargate", which the virus uses to release its nuclear material into the host cytoplasm.

They live in the cytoplasm of amoeboid protists called Acanthamoeba, which is a relatively widespread genus of amoeba. Previous studies on protozoan symbionts have revealed numerous types of intracellular bacteria in various Acanthamoeba species. The relatives of Megavirus are also hosted by Acanthamoeba, and are called Mimiviruses. The authors propose a family called Megaviridae that includes Megavirus, Mimivirus, and their relatives.

What more, it isn't just the largest known virus in terms of physical size. The information that it carries around in its genome is also large, weighing in at 1 259 197 base pairs. This is actually bigger than 8.4% of known bacterial genomes (according to the figures available on the NCBI website).

As an exercise I looked up information on bacterial and viral genome sizes from the NCBI Genome website. Go to "browse by organism groups" and you can download tables of genome information there. Fellow microbiologist blogger Guus Roeselers in the Netherlands points out that it is "remarkably easy to make some highly illustrative graphs."

I plotted a histogram of bacterial genome sizes (below) and as you can see, Megavirus has a genome size that would put some bacteria to shame (red triangle)!
Histogram of bacterial genome sizes, with red triangle marking the genome size of Megavirus chilensis.
What about other viruses? The distribution of viral genome sizes is more complicated than the bacterial case. There's a sharp peak at less than 50 kilobases (1 kilobase = 1000 nucleotides); the mean genome size is just over 31 kb. (NB: I calculated this based on total genome size, adding together all the segments for viruses with multiple nucleic acid segments). The previous record holder for largest viral genome is a mimivirus, also hosted by an acanthamoeba, that is 77 kb smaller.
Histogram of viral genome sizes, with red triangle marking genome size of Megavirus chilensis.
The very smallest genomes belong to the viral satellites. These are nucleic acid particles that can only replicate when the host cell is co-infected with a "helper virus". Entering the world of viruses is like walking into the verse by Jonathan Swift:
"So nat'ralists observe, a flea
Hath smaller fleas that on him prey,
And these have smaller fleas that bite 'em,
And so proceed ad infinitum."
At some point the boundary between "virus" and "selfish genetic element" blurs, and indeed some have even speculated that viruses are themselves selfish genes that have literally gone wild. (Digression: We know that some cancerous tumors can "break free" in such a manner too.)

Returning to Megavirus, this discussion has some relevance to the question of its origins: where do Megavirus and the other Megaviridae come from? When the scientists looked at the genome of Megavirus and mimiviruses, they found many genes that haven't been found in viruses before, but only in cellular organisms.

Several of these genes are involved protein translation. When we learn about viruses, we're usually told that they rely solely on the host translational machinery to produce their proteins, but Megavirus here may not be as dependent as other viruses. Megavirus has genes coding for aminoacyl-tRNA synthetases, which make the complexes of tRNA and amino acid that are brought together to string a new polypeptide chain during translation. Genes in this family have previously been found in mimiviruses. Megavirus not only has relatives to some of these genes, but also other genes in this family that have not been found in mimiviruses.

Could they have been acquired by horizontal gene transfer? Perhaps. But because the genes have relatives in mimiviruses, they were likely to have been present in the common ancestor of mimiviruses and Megavirus.

Megavirus also has DNA repair genes related to those in mimiviruses. These genes are unusually abundant in both these viruses, and Megavirus seems to be even more resistant to DNA damage by UV radiation than mimivirus!

The presence of yet more protein-translation genes in Megavirus, and the nature of the genes that it shares with other related large viruses leads the authors of this study to favor one hypothesis of giant virus origins: reduction from a cellular ancestor. They believe that it's more likely in this case that a cell somehow lost enough of its genome while turning viral, than it is that a virus accreted lots of cellular genes from its hosts or other sources to result in an enlarged genome.

The origins of viruses in general will still be debated for some time to come. But it is likely that any discussion will now have to factor in the example of this "dwarf among cells, but giant among viruses!"

Arslan D, Legendre M, Seltzer V, Abergel C, Claverie JM (2011) Distant Mimivirus relative with a larger genome highlights the fundamental features of Megaviridae. Proceedings of the National Academy of Sciences USA, published online before print, 10 Oct 2011, doi: 10.1073/pnas.1110889108.

1 comment:

Red Helix said...

this is a verry exciting blog post , informative and well writen.

exciting stuff