Tuesday, April 03, 2012

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: http://precedings.nature.com/documents/3886/version/1). 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.


  1. Now that Jonathan put me on the spot as a ‘stranger,’ I would like to outline a few things about me, focusing on ideas. Because of size limits for comments, I’ll post this in 2 parts.

    Part I: I’ll start with UC Davis, Jonathan’s academic home, where I spent a good part of 1984 as a guest fellow in Francisco Ayala’s lab in the Dept. of Genetics. Of note, while there, I proposed a novel approach for automated DNA sequencing, which is now called ‘sequencing by synthesis.’ Dr. Raymond Rodriquez, one of the pioneers of genetic engineering, who is still at UC Davis, directed me to some of his fellows at Genentech Inc. where I presented the idea. The technology for putting this novel approach into practice, however, was not quite there yet, so the idea went down the tubes; well, not really, as it is now among the ‘the next generation’ sequencing technologies.

    After abandoning a PhD program in BioPsychology on learning and memory at UGA, I enrolled at Emory U, Microbiology and Immunology, where I studied gene expression using an in vitro transcription system and an adenovirus gene as a model. The experimental work was solid, but more interesting was an associated hypothesis explaining a trio of rather puzzling features of RNA Pol III and its genes: Pol III, which is the largest of the 3 eukaryal RNA polymerases, usually transcribe very short genes (e.g. tRNA genes), which have internal promoter elements and are transcribed at a very high rate. The hypothesis that I proposed to explain these features was that, unlike the other RNA polymerases, Pol III and its transcription complexes go through multiple rounds of transcription without leaving the DNA template, a rather extraordinary evolutionary adaptation. I don’t know the current status of this hypothesis, but it was consistent with the data and it made evolutionary sense.

    While at Emory, I published several other hypotheses, including one about the evolution and function of ‘junk’ or non-coding DNA (ncDNA), one of the most prominent and puzzling eukaryal genomic features. According to this hypothesis (http://www.ncbi.nlm.nih.gov/pubmed/2156137), ncDNA (including introns) evolved primarily as a genomic protective mechanism against insertion mutagenesis by serving as a sink for the integration of proviral genomes and other endogenous mobile genetic elements. An updated version of this hypothesis is presented in the recent Nature Precedings series (http://precedings.nature.com/documents/3888/version/1). Maybe Jonathan’s brother Michael Eisen can discuss this hypothesis in his blog sensitively entitled: ‘it is NOT junk’ (http://www.michaeleisen.org/blog/).

  2. Part II. Since Emory, I have been at CDC. Most of my early work here was on molecular epidemiology and pathogenesis of HIV, including work on the identification of new HIV-1 subtypes, as well as various HIV transmission cases, such the infamous ‘Florida dentist case’ (http://www.ncbi.nlm.nih.gov/pubmed/1589796). More recently, I have been involved in studying the molecular epidemiology and pathogenesis of STD microbial pathogens, including C. trachomatis and T. vaginalis, as well as other public health issues.

    About five years ago, I intended to write a short note in order to ‘celebrate’ a quarter of century since I published the original paper on the origin and nature of viruses (http://www.ncbi.nlm.nih.gov/pubmed/6672474). To make a long story short, that note turned into the series of papers I posted in Nature Precedings, which tackle some of the fundamental transitions in the history of life. These papers contain several novel ideas and hypotheses, which I intended to develop in time.

    Because of the medical and public health significance and the urgency associated with Creutzfeldt-Jakob disease and other neurodegenerative disorders, such Alzheimer’s disease and Parkinson’s disease, in the last few years I focused on developing the ideas associated with the paper “Endogenous Viral Etiology of Prion Diseases” (see the comments section of the paper at: http://precedings.nature.com/documents/3887/version/1 and a recent summary posted at: http://www.alzforum.org/res/adh/cur/bandea/default.asp). The strength of the new unifying hypothesis that it is fully consistent with the vast amounts of experimental data and observations in these fields and that it explains many of their puzzling features; moreover, unlike the current working hypotheses, it makes biological and evolutionary sense. The new paradigm, however, challenges the prion hypothesis and the protein misfolding concept, which have directed most of the work in these fields for decades. As you can imagine, challenging these working hypotheses, which have been embraced by an entire generation of researchers, is difficult, to say the least, but I think it is getting there (see a comment I just posted on a Science article at: http://comments.sciencemag.org/content/10.1126/science.1219834).

    Back to the evolutionary origin and nature of viruses, it seems that my old hypothesis is getting some baby legs (e.g. http://www.virology.ws/2010/07/22/the-virus-and-the-virion/ and http://www.ncbi.nlm.nih.gov/pubmed/20198436), but we’ll see if it can eventually do the walk. There are hundreds a papers on the evolution of viruses and, although the data and analyses are highly valuable, their overall interpretation and integration might not be up to par, in some cases even flirting with pseudoscience. That’s the message I have tried to convey in a recent comment (http://precedings.nature.com/documents/3886/version/1) in which I asked the question: if all the parasitic or endosymbiotic cellular organisms evolved toward smaller genomes and lower complexity, why would viral lineages evolve any other way? I have circulated this comment among the scientists in this field but I have yet to get an answer, although I did received some positive feedback on top of mostly calls for retracting the comment.

    I’ll stop here, but not before thanking Jonathan for inviting me to be one of his guests and reminding him about my question regarding the Tree of Life.

  3. Looks like another 'legend in their own mind' deal...


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