Viruses evolve to play by host rules, according to University of Pennsylvania researchers

[Sally Furniss]

Viruses evolve to play by host rules, according to University of Pennsylvania researchers

PHILADELPHIA -- Biologists at the University of Pennsylvania and Harvard University have examined the complete genomes of viruses that infect the bacteria E. coli, P. aeruginosa and L. lactis and have found that many of these viral genomes exhibit codon bias, the tendency to preferentially encode a protein with a particular spelling.
Researchers analyzed patterns of codon usage across 74 bacteriophages using the concept of a "genome landscape," a method of visualizing long-range patterns in a genome sequence.
Their findings extend the translational theory of codon bias to the viral kingdom, demonstrating that the viral genome is selected to obey the preferences of its host.
“The host bacterium is exerting a strong evolutionary pressure on the virus,” Joshua Plotkin, lead author and assistant professor in the Department of Biology at Penn, said. “This happens because a virus must hijack the machinery of its host in order to reproduce. We are seeing that viruses are forced to adopt the particular codon choices preferred by the bacterium they infect.”
The study found that each bacterium has a preferred way of spelling its genes. And it appears that viruses that infect a bacterium spell their own genes in the same way the bacterium does, obeying the rules of its host and demonstrating co-evolutionary behavior.
“Like a bee and a flower, an example of co-evolution between two large organisms, the same fundamental biological processes operate between two small organisms, as reflected in their genome sequences,” Plotkin said.
Moreover, the team found that the degree of codon bias varies across the viral genome. By comparing the observed genomes to randomly drawn genomes, the team demonstrated that the regions of high codon bias in these viral genomes often coincide with regions encoding structural proteins. Thus, the proteins that a virus needs to produce at high levels utilize the same encoding as its host organism does for highly expressed proteins.
Any protein can be encoded by multiple, synonymous spellings, but organisms typically prefer one spelling over others, a phenomenon known as codon bias. Codon bias is generally understood to result from selection for the synonymous spelling that maximizes the rate and accuracy of protein production.

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The study, appearing in the current issue of the journal Public Library of Science Computational Biology, was performed by Plotkin and Grzegorz Kudla of the Department of Biology in the School of Afrts and Sciences at Penn and Julius Lucks and David Nelson of Harvard University.
The study was supported by grants from the Burroughs Wellcome Fund and the National Science Foundation.

http://www.eurekalert.org/pub_releases/2008-03/uop-vet030308.php

 

[gsgs]

Re: Viruses evolve to play by host rules, according to University of Pennsylvania researchers

the question is : how do the viruses achieve this ?
Is there some force during replication to distinguish
synonymous changes ? How does the virus even know,
what the preferred host-encodings are ?

OK, it's here:

http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000001

but slow loading for me actually. Should we copy it to here ?


Author Summary
Any protein can be encoded by multiple, synonymous spellings. But organisms typically prefer one spelling over another—a phenomenon known as codon bias. Codon bias is generally understood to result from selection for synonymous spellings that increase the rate and accuracy of protein translation. In this work, we have examined the complete genomes of all sequenced viruses that infect the bacteria E. coli, P. aeruginosa, and L. lactis, and have found that many of these viral genomes also exhibit codon bias. Moreover, the degree of codon bias varies across the viral genome, as visualized using a technique called a “genome landscape.” By comparing the observed genomes to randomly drawn genomes, we demonstrate that the regions of high codon bias in these viral genomes often coincide with regions encoding structural proteins. Thus, the proteins that a virus needs to produce in high copy number utilize the same encoding as its host organism does for highly expressed proteins. Our results extend the translational theory of codon bias to the viral kingdom: parts of the viral genome are selected to obey the preferences of its host.


one reference about influenza:
20. Plotkin JB, Dushoff J (2003) Codon bias and frequency-dependent selection on the hemagglutinin epitopes of Influenza A virus. Proc Natl Acad Sci U S A 100: 7152–7157.
http://www.pnas.org/cgi/content/full/100/12/7152


I think, we talked about this at fluwiki in 2006. I don't remember much from that discussion.

Abstract of that 2003-paper:

Although the surface proteins of human influenza A virus evolve rapidly and continually produce antigenic variants, the internal viral genes acquire mutations very gradually. In this paper, we analyze the sequence evolution of three influenza A genes over the past two decades. We study codon usage as a discriminating signature of gene- and even residue-specific diversifying and purifying selection. Nonrandom codon choice can increase or decrease the effective local substitution rate. We demonstrate that the codons of hemagglutinin, particularly those in the antibody-combining regions, are significantly biased toward substitutional point mutations relative to the codons of other influenza virus genes. We discuss the evolutionary interpretation and implications of these biases for hemagglutinin's antigenic evolution. We also introduce information-theoretic methods that use sequence data to detect regions of recent positive selection and potential protein conformational changes.



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Influenza A virus is a negative-stranded RNA virus that infects roughly one-fifth of the human population each year, causing significant mortality and morbidity worldwide (1). The surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) are the most important targets for the human immune system. Gradual mutations to HA continually produce immunologically distinct strains of the virus that cause annual outbreaks. An influenza infection brings lasting immunity to the infecting strain, but most people are susceptible to reinfection by a new strain within a few years.
The HA protein consists of two chains, HA1 and HA2, respectively 329 and 175 residues long. Phylogenetic reconstructions (2, 3) reveal that modifications to HA1, the immunogenic part of HA, accrue at a dramatic rate. Those sites of HA1 involved in antigen determination exhibit significantly more nonsynonymous than synonymous nucleotide substitutions (4, 5), whereas the remaining sites show the more common pattern of primarily synonymous variation. These observations suggest that HA1 is undergoing diversifying, or "positive," Darwinian selection (6). Because immunity to an infecting strain is longlasting, and because influenza infects a large proportion of its host population each year, the antigenic regions of HA1 experience strong frequency-dependent selection for novel functional variants.

Although the influenza A NA gene also acquires substitutions rapidly, NA is not considered as important an antigenic determinant as HA (7) and is less prevalent than HA on the surface of the viral particle (8). Moreover, antibodies to NA do not neutralize the virus as do HA antibodies (9–11).

The mechanism of influenza A's antigenic plasticity, that is, how the virus continually evades immunity by producing variant strains, remains an outstanding evolutionary problem with obvious practical implications. The structure of the HA heterotrimer solved for a 1968 virus strain (12, 13), along with matrices of immunological crossreaction assays (14), has led to the identification of five antibody-combining regions, or epitopes, of the HA protein. Epitopic residues exhibit greater variability, higher ratios of replacement to silent mutations, and greater correlation with future phylogenetic trajectory (15).

Nonepitopic sites of HA do not evolve as rapidly as epitopic sites. Similarly, internal viral proteins such as matrix (M1, M2), polymerase (PB1, PB2), nucleoprotein (NP), and nonstructural protein accrue mutations very gradually, presumably because, compared to epitopic residues of HA, (i) they are hidden from antibodies and thus under less selective pressure to change, and (ii) they are structurally and functionally more fragile and cannot sustain significant mutation. As a result, influenza faces an intragenomic conflict over the mutation rate: certain genes, and specific residues within those genes, experience frequency-dependent selection to change, whereas other genes experience purifying selection to remain fixed.

In this paper, we address influenza's gene- and site-specific requirements for antigenic plasticity. We discuss the notion of codon usage biased toward substitutional or stereochemical diversification. We report that codons of HA, and particularly epitopic regions of HA, are significantly biased toward diversification relative to other influenza virus genes. We discuss the importance of these biases for HA evolution. We also introduce information-theoretic methods to detect regions of recent positive selection and potential protein conformational changes, on the basis of sequence data alone.