I've been told to make a selective pressure analysis of a hypervariable region of a viral genome. I have aligned my sequences, removed stop codons and I did some tests I've met in publications like Codon-based Z-Test of Selection in Mega 7, MEME, FEL, SLAC methods on Datamonkey server, and tried to mesure synonymous versus non-synonymous mutation ration with the SNAP program. But I have absolutely no idea what to do with all the obtained numbers and how to interpret the results. Can somebody simply explain the selective pressure analisys to me?
Dear Irina...
This link looks helpful, you may follow the same way of data interpreting .
Article Phylogenomic analysis of natural selection pressure in Strep...
Best Luck.
There are many different types of "hypervariable" regions in viral genomes. So even the best tools don't always work well with each type. For example, in the HIV-1 M group viral genomes, the variable loops of the envelope protein gain and loose length (insertions and deletions) and especially gain and loose N-linked glycosylation sites, or alter the position of glycosylation sites. The Gag gene and some non-coding regions of the HIV genome also evolve much faster than the average, sometimes via insertion/deletion and sometimes through single-base changes. DataMonkey, SNAP and other tools are far better at analyzing base substitution evolution than they are at analyzing insertion/deletion evolution.
For most analyses, it is very helpful to compare your data and analysis results to data and analysis results from related organisms (other viruses in your case) where more is known about the selection pressures (antibody selection on envelope, CTL selection on Gag, drug selection on Pol, etc in HIV-1) to get a feel for what types of results are very clear and what types of results are more subtle or missed by a given analysis method.
HIV is a rather rare exception among viruses, because it remains in each host individual for years, interacting with the individual's unique immune system. Many or most viruses are rapidly eliminated by immune response and have already moved on to infect other individuals before the current host response has shaped their evolution significantly. Some viruses face "herd immunity" challenges where most individuals were infected with "last year's" strain and are only susceptible to new variants, but more often these types of viruses instead rely on newborn infant hosts who are not yet immune, or migration to new populations.
The Streptococcus genomics paper suggested by Ayoob Obaid Alfalahi above is a different type of analysis that you are probably looking at. There is quite a bit of difference between studying the average behavior of entire genes/proteins or operons, and studying the selection pressure on single codons or amino acids within a gene/protein. The common dogma is that whole genes or operons are negatively or positively selected, and this is true to some degree. But it is more accurate to say that essentially all protein-coding genes (and structural RNA genes too) are under massive negative selection pressure to remain functional, and in most cases some regions of those genes are under less negative selection pressure and allowed to change a bit without reducing fitness. True positive selection, where the new variant is more fit than the ancestor, is quite rare.
Bacteria exchange genes rather regularly, via plasmids, phages and other mechanisms and we often see entire genes or operons making a selective sweep through a genus or species. Most viruses have very small genomes and experience less recombination between lineages. But some viruses do engage in recombination and this can confound studies of selection pressures. If one entire gene is twice or ten-fold more diverse in your virus than another gene is, it could be do to recombination rather than very rapid evolution of that gene.
for selection presure analysis you can read this book that might be helpful:
Molecular Evolution and Phylogenetics
Masatoshi Nei, Sudhir Kumar
Oxford University Press, 2000 - Medical - 333 pages
Thank you, Masoud, I will definitely read that book.
Mr. Foley, thank you very, very much. May I ask for more detailed help in private message? I'm working with respiratory-syncytial virus, in particular second hypervariable region of the attachment glycoprotein, which is heavily N- and O-glycosylated.
Yes, it is fine if you write to my regular email address. btf at
lanl.gov is my address.
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