Viruses viruses viruses viruses viruses viruses viruses.

Actually, the title is clearly insufficient. [Viruses]^100 or something like that would be better.

And here is a story by Michaeleen Doucleff from NPR about viruses in the human microbiome with some quotes from me.

Crosspost from microBEnet: Some interesting new papers on functional analysius of metagenomics

Crossposting from microBEnet:

Some new papers that may be of interest to people:

Nathan Wolfe talk at #UCDavis Wrap Up #Storify #Viruses

Nathan Wolfe talked at UC Davis yesterday.  I met with him for 30 minutes just before his talk.  Many times I feel that 30 minutes is more than enough when meeting with outside seminar speakers.  I definitely would have enjoyed more time with Wolfe – he does some pretty fascinating stuff.

Anyway – I escorted him to his talk and then I took notes for it on Twitter as did Pam Ronald (who was sitting next to me).  I then made a “Storification” of the talk (using the Storify.Com system).

This is below:[<a href=”” target=”_blank”>View the story “Nathan Wolfe talk at #UCDavis” on Storify</a>]

Guest Post on Viruses from Claudiu Bandea

From here.

Guest Post Today from Claudiu Bandea .

Claudiu wrote to me after my paper on “Stalking the Fourth Domain” came out.

He wrote


I posted a comment on your ‘PLoSOne paper’ blog, but I thought of sending you this mail. 

You might be interested in taking a look at the attached paper presenting a fusion model for the origin of ‘ancestral viruses’ from parasitic or symbiotic cellular species, and its implication for the evolution of viruses and cellular domains, which I’m attaching here (you can see the entire series, including comments, at: Possibly, the novel sequences you discovered belong to such ‘transitional forms’ between the cellular domains and the viral domains.

I know it’s a lot of material, but you might want to focus on Fig. 4 and the related discussion about TOLs from the perspective of the current hypotheses on origin and evolution of viruses. Because of your interest in TOL, I want to ask your thoughts on the difference between the concept of TOL based on the line-of-descent, the ways it was historically intended, and the current approaches of using (mostly) sequences which, as you know, due to LGT might not necessarily reflect the line-of-descent relationships.



After a bit of a back and forth I offered to let him write a guest post on my blog about this. He accepted my offer.  I note – I am not endorsing any of his ideas here and to be honest I have not read his papers he refers to – I have skimmed them and the seem interesting but have not had a chance to read them.  I also note – I am a bit uncomfortable with the fact that I cannot seem to find any Web Profile / Web Site / Blog / etc. with more detail about him and his work.  On one hand – ideas are ideas and they can and should stand on their own.  On the other hand context is useful in many cases and I feel like I am missing some context here.  He works at the CDC but I am not sure what he actually does there.  But in the interest of open discussion of ideas and since, well, not having a web site is certainly not a crime, his post is below.

The most efficient way of silencing ideas is not by criticizing them but by pretending they don’t exist. The antidote might be the blogging world.

A couple of decades ago, I published a novel model on the evolutionary origin of ancestral viral lineages. Recently, I updated this model and integrated it into an ambitious unifying scenario on the origin and evolution of cellular and viral domains, including the origin of life; well, that might have just buried it so deep that it’s gone for good even for those with an open mind and noble intentions.

So, I would like to ask you the favor of reviewing and criticizing this model. As a primer, you might want to read a comment I posted last summer on a book review by Robin Weiss. The book was Carl Zimmer’s A Planet of Viruses and the review by Dr. Weiss, one of the most distinguished contemporary virologists, was entitled Potent Tiny Packages, which symbolizes our century-long perspective on the nature of viruses as virus particles. If we have reasons to call Earth a planet of viruses, as I think Carl successfully made the point, then viruses require our full attention, including the right to be correctly identified and to be included in the Tree of Life.

I know, this is a lot of material, but I hope you’ll find it interesting, and I would be thrilled to address your questions and listen to your ideas.

Classic papers in genetics and evolution that are available in Pubmed Central – Paper 1 – Luria and Delbruck on the origin of mutations

I am starting a new series here —- finding and writing about classic papers in Evolution and Genetics and Molecular Biology that are available for free in Pubmed Central. And though plenty of classic papers are not avilable, a good collection of them are.

My first selection is Luria and Delbrück’s paper from 1943 on the origin of mutations. This papers is near and dear to my heart in many ways and I still remember looking it up for the first time when I was an undergraduate. I was taking a class from Jennifer Doudna on the origin of life, and we had to write a paper as part of the class. In the class we had discussed a new paper by John Cairns and colleagues that revisitid the origin of mutations question. Cairns et al. result suggested to them at least that bacteria could pick and choose the mutations they needed for increased fitness in a particular situation (suggestive of so-called Lamarckian evolution to them). I was fascinated by this work (so much so, that it became the topic of my grad. school application essays and the topic of my first two years of PhD research in Phil Hanawalt’s Lab). So I chose to write a paper on the origin of mutations.

Obviously, to write such a paper I had to go to Luria and Delbrück’s work since they were the first to experimentally test the question of how much mutations pre-existed selection and how much they arose after selection. I stillremember sifting through the old journals in the library at Harvard to find this and turning the pages in teh dust covered volume to read it.

Luria and Delbrück chose as their experimental system resistance to bacteriaphage and their model organism, Escherichia coli. In their paper first the describe the theoretical underpinning of their wor. In their theory they come up with a way to do an experiment to test whether mutations pre-exist selection or arise in response to it – something now generally known as a fluctuation test. Basically the idea is simple. Take a particular form of the bacteria. Innoculate multiple test tubes with a small amount and let each test tube grow up to a dense culture. Then expose bacteria from each tube to the selective pressure. If the mutations pre-exist selection then there should be big differences between the replicate test tubes in the number of mutants since in some the mutation would arise early in the growth of the culture and in some they would arise late (this is known as a jackpot distribution). If the mutations arise after selection then each tube should have somewhat similar numbers (with some variation around a mean).

And when they did the experiments the results followed very closely the jackpot model. They stated:

We consider the above results as proof that in our case the resistance to virus is due to a heritable change of the bacterial cell which occurs independently of the action of the virus. It remains to be seen whether or not this is the general rule. There is reason to suspect that the mechanism is more complex in cases where the resistant culture develops only several days after lysis of the sensitive bacteria.

And thus they showed that mutations unequivocally pre-exist selection. Now, it turns out that their experiment had a flaw – since they were using a lethal selection (phage) the system did not really allow for a long period of time for the mutations after selection to arise (when your dead it is hard to generate mutations). The Cairns experiment (and Ryan’s before him) showed that some unusual results occurred if you used a non lethal selection. So one cannot really use Luria and Delbrück’s experiment to disprove the possibility that mutations arise after selection. Nevertheless, their proof that mutations can exist before selection was a fundamental discovery. And their methods were used throughout bacterial genetics for years (to this day in fact). For more detail see Access Excellence page about Luria and Delbruck.

This is such a fundmentally important paper, and it is great that this paper is available, free to all, in Pubmed Central. See below:

Mutations of Bacteria from Virus Sensitivity to Virus Resistance.
Luria SE, Delbrück M.

Genetics. 1943 Nov; 28(6): 491-511.
PMCID: 1209226
| Abstract | PDF-1.3M |

Difficult times in predicting flu evolution suggested by recent paper

There is a potentially controversial and very interesting article in the journal PLoS Pathogens on Flu Evolution. The study was led by Edward Holmes at Penn State, and co-authored by many researchers including colleagues of mine at my former institution TIGR. They performed a detailed evolutionary analysis of the cmplete genomes of 413 influenza A viruses of the H3N2 type (the H#N# system refers to the subtypes of Hemaglutanin and Neuraminidase genes).

The virus genomes were sequenced at TIGR using a high throughput flu viral genome sequencing protocol originally developed at described by Elodie Ghedin and colleagues here and here. The viruses they selected were from across New York State as part of a surveillance program.

Using a variety of evolutionary analyses including phylogenetic reconstructions and examination of substitution patterns, they come to a surprising conclusion – that

stochastic processes are more important in influenza virus evolution than previously thought, generating substantial genetic diversity in the short term

This may seem somewhat uninteresting to many out there but if true it is critically important in fighting flu and in understanding viral pathogen evolution. Right now there are substantial efforts to try and predict what future dominant flu strains will look like. These predictions tend to rely on assumptions that positive selection of viruses is critical in generating and maintaining diversity. If stochastic processes are as important as Holmes et al conclude, it would mean that more intensive monitoring of flu is needed in almost real time (since predicting random events tends to be, well, very hard).

I confess I have not tried to evaluate whether or not I think their conclusions are correct, but on first glance they seem sound. This just goes to show that general genomic surveys that try to be relatively unbiased in their sampling can reveal substantial novel patterns not seen before in highly target genome sequencing projects.

Viruses as food additives

I find it sad that the world has come to this. The FDA announced that it has approved the use of viruses as a food additive. The particular viruses (known as phage in this case) target and kill common bacterial pathogens found in meat. It is entirely possible that this treatment will lead to reduction in deaths and illnesses. However, it is also possible that there will be unexpected consequences of this treatment and thus anything like this should be done with caution. What saddens me about this whole thing is that it is the wrong way to go about solving the problem. Most of the problem comes from the fact that our meat today in this country does not come to us in reasonable condition. The animals are usually kept in unsanitary conditions where diseases and nasty pathogens are prevalent.

The best way to think about this in my opinion is what I read in The Omnivore’s Dilemma, the new book by Michael Pollan. In this book he talks about how animals now frequently live in what can be considered the equivalent of the slums of the industrial revolution. Cities of animals, frequently wallowing in excrement, is not the best way to prevent bad microbes from getting in our food.

So in recent years all sorts of practices have been developed to kill these microbes in food products. Irradiation, for example. And now, viruses, sprinkled on your meat, to keep the bacteria from growing too much. Give me meat from animals that have not been swimming in their own shit and piss and I will be happy to take my risks without dumping viruses on top.