Megavirus: A Mimivirus relative

This blog post is based on the paper discussed by myself and Mario Lewis in Friday’s seminar.

The discovery of Mimivirus; a large DNA virus infecting Acanthamoeba and the determination of its genome sequence forever changed how microbiologists looked at viruses. The Mimivirus genome encodes for 979 proteins, including 8 components central to protein translation, including the first four aminoacyl tRNA synthetases (AARS) ever found in a virus. Once the excitement of the Mimivirus discovery was contained, the next step was to assess whether these idiosyncrasies were anecdotal or deeply linked to the emergence and mode of evolution of giant DNA viruses. Giant DNA viruses are referred to as Megaviridae – the definition for which is a genome size of greater than 1000bp.
Through random sampling of aquatic environments followed by culturing on a panel of Acanthamoeba species, Megavirus chilensis, was isolated from sea water samples off the coast of Chile, but with capabilities of replicating in freshwater Acanthamoeba.
This paper presents an electron microscopy study of the Megavirus replication cycle in A. castellanii and an analysis of its genome.
The virion particles of both Mimivirus and Megavirus have a similar morphology; however, they can be easily distinguished even in mixed cultures through slight differences. Many of the structures described in Megavirus correspond to structures already described in Mimivirus.
Megavirus and Mimivirus were found to share 594 orthologous proteins unveiling a comprehensive distribution of similarity centred on an average of 50% identical residues, which were most likely inherited from a common ancestor. The corresponding gene set provides a minimum estimate of the core genome of ancestral Megaviridae.
As mentioned previously Mimivirus contains the first four AARS ever found in a virus, yet Megavirus exhibits a further three AARS, which offers strong support that the Megavirus/Mimivirus lineage evolved from an ancestral cellular genome by reductive evolution as opposed to the view these virus’s gained these genes through random horizontal gene transfer.
A main cause of divergence between Mimivirus and Megavirus seems to be the progressive accumulation of point mutations. 258 Megavirus protein coding sequences exhibit no obvious homolog in Mimivirus, and reciprocally 186 Mimivirus protein coding sequences exhibit no obvious homologs in Megavirus. More than 85% of these lineage specific protein coding sequences correspond to proteins without functional predictions. It is likely these correspond to lineage specific loses along the different branches. Genomic reduction is a universal, fast, irreversible process among many cellular parasitic microorganisms that may also apply to the evolution of Megaviridae from their more complex ancestors.
Differential expansion or reduction of large paralogous families is also another reason for the difference in gene content of the two Megaviridae.

In conclusion there are two opposing view for the origin of Mimivirus-like genomes. The view of this paper is origination from an even more complex viral ancestor, itself derived from an ancestral cellular genome. The origin of the many cell-specific functions uniquely encoded by Mimivirus is central to this. This paper criticises the other view of horizontal gene transfer, that Megaviridae are simply efficient gene ‘pickpockets’. The analysis of more Megaviridae will provide an increasingly clearer picture of this evolutionary process.

A review of;
Arslan D, Legendre M, Seltzer V, Abergel C and Claverie JM (2011) ‘Distant Mimivirus relative with a larger genome highlights the fundamental features of Megaviridae’ PNAS. 108(42), 17486-17491.