Directed evolution suggests way viruses could have evolved

Donald Hilvert of the Swiss Federal Institute of Technology (ETH) Zurich and his colleagues show that the this hypothesis is plausible by making it happen in the lab ( Science 2021, DOI: 10.1126/science.abg2822). “You can take a bacterial protein that has no starting affinity for nucleic acids and teach it how to bind its own encoding mRNA, package it, and protect it against nucleases,” Hilvert says.

The researchers started with a bacterial enzyme called lumazine synthase, which naturally forms 60-subunit nanoscale cages. The researchers redesigned the protein by adding a peptide that tightly binds an RNA sequence called BoxB; this peptide was designed to trap the RNA the team hoped to evolve the protein to package. Meanwhile, they added BoxB to both ends of the RNA sequence encoding the protein. They then subjected the protein to multiple rounds of directed evolution in which they randomly mutated the gene encoding the protein and selected for variants that could package the target RNA and protect it from nucleic acid–cleaving enzymes.

The resulting container combined 240 protein subunits and efficiently packaged the full-length RNA. Intermediate versions had fewer subunits with large pores that let nucleic acid–cleaving enzymes in. During evolution, the protein underwent structural changes in which monomers interlaced with one another by swapping domains and forming trimeric building blocks. Those building blocks further assembled into pentamers of trimers. The final capsid consisted of 12 pentamers of trimers plus an additional 20 trimers in a spherical shape with small pores. The interlacing reduces the size of the pores compared to the original, which helps block nucleases.

The work is a “multidimensional tour de force that experimentally recapitulates processes by which viruses might have emerged from free-living organisms,” says Charles W. Carter Jr., a structural biologist at the University of North Carolina at Chapel Hill.

https://science.sciencemag.org/content/372/6547/1220

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Fascinating. I’d like to read the paper but don’t have access. I’d be grateful for a copy if anyone has.

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Preprint version can be found at https://www.biorxiv.org/content/biorxiv/early/2020/12/23/2020.12.23.423990.full.pdf

(Hat-tip Google Scholar)

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I am amazed by the fact that the selection protocol was capable of optimizing multiple aspects of the viral packaging.

The complexity of the packaging capsid structure grew much larger, from 60 to 240 subunits, the pores in the structure got smaller, and the selectivity and specificity of the capsid protein increased towards it’s own mRNA instead of just any and all RNA. And then there is the fact that the packaging protein also saw a considerable structural alteration, depicted well in figure 4b+c.

And that this was accomplished by simply selecting for capsids that capture their own mRNA transcripts, then by subjecting the particles to digestion by increasingly smaller RNase enzymes.

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Which, notably, does not require intelligent guidance and is an obvious natural mechanism of selection.

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Well, yes and obvious to us, but extremely unlikely to be obvious to any of those who argue against evolutionary biology here.

Perhaps it would be more helpful if you explained it to them instead of asserting that it is obvious.

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