Sunday, January 09, 2011

House Too Small? – Overlapping Genes in Viruses

Protein coding genes are complicated things: the four bases of DNA are arranged into triplet codons, each of which codes for one of 21 (more or less) amino acids, which are strung up in a polypeptide chain, folded into a complex 3-dimensional structure where precise shape and chemistry determines function... It would seem that any perturbation would throw this finely-tuned system off-kilter.

Even more outrageous is the notion that genes can overlap and still code for perfectly functional proteins, because this implies that, for part of the gene at least, a different reading frame still has functional meaning. This flies against our intuition that frame-shift mutations are the deadliest of all, and has been likened to taking a paragraph of text, moving all the spaces between words down by a character, and still being able to read it, but this time with a completely different meaning!

Viruses, though, are capable of this sort of contortion, and a number of hypotheses have been proposed to explain why they find it necessary to do so. Is it a way to reduce the overall genome length in the face of a high mutation rate? Or is it a means to couple together the expression of more than one gene? Looking at a number of viral genomes, a team from Italy and the UK claim to have found the reason: overlapping genes are a response to the constraints placed by viral capsid size.

For viruses that use RNA for their genetic material, there is a known inverse relationship between genome size and gene overlap: the longer the genome, the less gene overlap is present. They confirmed that this also held for DNA viruses. But when they grouped viruses by the kind of capsids they have–icosahedral vs. flexible–they found that this relationship is strong in the icosahedral capsid viruses, but weak in those with flexible capsids. Capsids are protein 'coats' that encase the viral genome; icosahedral capsids are particularly rigid and constrained in size, because their geometric configuration (icosahedra are one of the five Platonic solids of classical geometry) is the result of the interlocking of the protein units that make up the coat. There are precise mathematical rules that govern the assembly of these units.

Icosahedral Adenoviruses
Icosahedral adenoviruses (electron micrographs) with cartoon of icosahedron. (Wikimedia Commons)

On the surface, it seems like an extreme solution, even reminiscent of the infamous Bed of Procrustes. These viruses appear to have found a way of surviving the ordeal. It's so striking because we wouldn't expect to see what is patently a physical constraint leaving such a distinctive genomic signature, the latter being strictly informational. At the molecular level, though, there may be a fuzzier line between the two.

This is one of those things which writers used to attribute to the 'ingenuity of Nature', but speaking in materialist terms:
"In effect, the capsid poses an engineering problem for the creation of genomic novelty, and gene overlap is the way around it."

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