Tag: open access

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 |

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This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

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Shameless Self Promotion

OK. I know I am not supposed to do this. But hey, are there really any rules for blogs?

I got my first major local press story since moving to Davis yesterday. The Sacramento News and Review ran a cover story on the U. C. Davis Genome Center, featuring me, Katie Pollard, and the director of the center Richard Michelmore. I of course do not recall saying any of the things that I am quoted saying but I certainly recall saying things close to what was quoted so in this case the reporter (Ralph Brave) seems to have done a fair job. I guess I would quibble a tiny bit with my portrayal in terms of the discussion of synthetic biology (I believe it is a powerful tool but that the practitioners downplay the risks).

The best part of the story – they featured my work on the glassy winged sharpshooter symbionts that we published in PLoS Biology earlier this year. That is (hopefully) good for me since the sharpshooter is a big deal out here in N. California since it is a vector for Pierce’s Disease in grapes. Plus, they were able to use a figure from my paper since of course, the paper in fully Open Access. So my work gets some extra exposure that might have been more difficult for the paper to pull off if it was published in a non Open Access journal. In essence, Open Access publishing is the gift that keeps on giving. As long as I keep getting credit for it, it is great for me that people do not have to get permission or pay a fee to use figures from my papers.

Added afterwards:

  • Egghead ran a story on this
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This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

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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.

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This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

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Has your scientific research been wasted?

I had a good Thanksgiving weekend this year – spending time with family and friends. But as I go back to work this week I have now gotten somewhat depressed over something I did Sunday night. I decided to remove myself from the UC Davis internet proxy to see how many of my past papers that I have published I can obtain without the UC subscriptions. So I went to pubmed, and typed in my name (Eisen JA) and got most of my papers, which are listed at the bottom of this blog (some do not come up due to publication off the pubmed grid or due to co-authors screwing up my initials). (NOTE  – LISTING DELETED 4/09 BECAUSE THE FORMATTING IS ALL MESSED UP)

And then I went to see how many of my papers were freely available and how many were not. What I was most interested in was – what is the deal with papers I wrote before becoming an Open Access convert? For many it is easy to figure out if they are freely available – Pubmed has a link saying “Free in PMC” which refers to Pubmed Central. For others, it was a little trickier.

The results were both good and bad and a summary is below. A few things struck me. First, a lot of my life’s work is not readily available without paying other for it. In the day and age of the internet, this means that these papers will simply be read less and less as time goes by. And that makes me very sad. If I had chosen to publish those papers in other journals, anyone in the world could get them at any time. Thankfully I did publish many papers in journals like PNAS, and ASM journals, and NAR – journals that have now decided to release them to Pubmed Central. And also thankfully (but less so) I published some papers in journals that have at least made them freely available on their web sites.

Most surprisingly to me is that a reasonable number of my papers in Nature are freely available on the Nature web site as part of their Genomics Gateway program. Nature deserves serious kudos for doing this and they stand out compared to Elsevier journals (which do not seem to ever do this) and even Science. This is disappointing as Science is published by a scientific society but apparently does not seem to care much about access to publications. Nature, a commercial publisher, is in my opinion doing more for scientific openness than Science. Now, Nature has a long way to go, but I am SO glad I listened to their editors like Chris Gunter and Tanguy Chouard who made a big deal about the Genome papers being free. I did not think it was that big a deal, but in retrospect they were ahead of me in thinking about availability. Plus Nature clearly makes more of an effort to provide free online material than they have to – and certainly make more available than Science.

So in the end – I am sad about my partially wasted past. But I am pleasantly surprised that at least some papers I thought would be more restricted are actually free (although only on the Publishers site for now – Hopefully these journals will submit them to PMC at some point). I guess – you win some and you lose some and some are somewhere in between.

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Summary of openness — other scientists should do this exercise

In Pubmed Central and Open Access

Available free on publisher’s sites (notideal but better than nothing)

Must buy paper

Not available anywhere

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This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

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A call for Open Access supporters to favor grant proposals from researchers promising Open Access publishing

In the world of scientific research, perhaps the most critical step is the acquisition of funding to do research. A key component of grant reviews these days are “Release Policies” for data, tools and research materials. In general, the more “Open” one is with these release policies, the more likely one is to get a grant. This of course makes great sense. If one is going to keep ones data or tools or material private for as long as possible, then one is not advancing science as rapidly as someone else who did the same work but also released everything rapidly.

I believe now is the time for the same thing to be done regarding Open Acces publishing. One can use the same litmus test here. Imagine two grant proposals, to do identical work. And furthermore, asssume the researchers will succeed in their work. And one researcher promised to publish in an Open Access manner while the other promises to publish in a non Open manner. Again, assuming everything else is equal, I think the proposal promising Open Access publishing HAS to be scored higher than the one promising non Open publishing.

Certainly in NSF proposals this could be considered as a component of the Broader Impact criteria and people should write it into their grants. If anyone has any ideas about how this could be specifically incorporated into NIH or DOE or other grants please let me know.

So I call on researchers who support Open Access publishing in any way to start to bring this up on grant panels and in grant reviews. And to score proposals accordingly. That is, if someone has a record of publishing in Open Access journals, they should be moved up a notch compared to others. Just how much is a “notch”. That should be up to individuals. But it is the principle here that is important – publishing in Open Access journals should be a component of grant reviews.

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This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

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Paramecium whining

I just got an announcement from Linda Sperling, announcing the publication of a paper on the Paramecium genome

Dear ciliate researcher,

We are pleased to announce that the Paramecium genome article is now available as an advanced online publication at the following address:

http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature05230.html

We thank all of you for your interest and support.

Jean Cohen and Linda Sperling

Linda Sperling
Centre de Génétique Moléculaire
CNRS
Avenue de la Terrasse
91198 Gif-sur-Yvette CEDEX
FRANCE

sperling@cgm.cnrs-gif.fr
+33 (0)1 69 82 32 09 (telephone)
+33 (0)1 69 82 31 50 (fax)
http://paramecium.cgm.cnrs-gif.fr/

She sent this to an email list for ciliate researchers. I am writing about this in my blog because a blog is where you are supposed to write things these days when you are pissed off. Why am I pissed off about this? Well, the Paramecium paper makes no mention whatsoever of our paper on the genome of a close relative of Paramecium (Tetrahymena thermohila for those interested) which was published in August. And they do not even explicitly mention the Tetrahymena genome project (even though they say they took our data and used it). I guess I am not too surprised since their paper is published in Nature, which recently seems to be taking many liberties with referencing things in Open Access journals (ours was in PLoS Biology).

What is most annoying about this whole thing is that Linda Sperling is on the Scientific Advisory Board of our project, and has been privy to all of our work from the inside and was I am sure fully aware of our paper being accepted long before theirs was. Common courtesy in science would have been for them to have made a reference to our paper in press or at least our project. But for whatever reason, they carefulyl crafter their words to make no mention of our work. Interestingly, here is the email I sent to the same ciliate list on August 29, 2006

For those interested, our paper on the Tetrahymena MAC genome has been published online at PLoS Biology

http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0040286

Jonathan Eisen

Strikingly, their paper was then accepted August 31, 2006. I hate to believe in conspiracies, but it seems just a little too coincidental that their was accepted just after ours was published. And yet still no mention of our work in their paper. Hmmm …

Fortunately, since our paper was in PLoS Biology, they cannot say “sorry – we did not have access to it.” Whatever they say, I can say clearly that Linda Sperling will not be invited to our next SAB meeting.

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This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

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Flu Evolution Revisited and Biology Direct’s Foray into Open Peer Review

Anyone interested in scientific publishing and/or the flu should check out a new paper in the journal Biology Direct. The paper suggests a new way of thinking about flu evolution. Whether you agree with the authors or not (I am still not sure), what is most interesting about this to me is that the reviews are posted online as are the authors responses. See the paper here and some stories about it here and here.

Biology Direct is an Open Access journal that is experimenting with the peer review system. Their experiment is quite intriguing in its methods. For details see here and here.
Basically, the author is charged with selecting reviewers and then getting the reviews. Then the paper can be published along with the reviews, whether they were positive or negative. The author can make changes based on the reviews or can choose not to. Thus someone could publish complete crap, but since the reviewers will be named publically, hopefully the reviews will indicatethat it is crap. The key to this is that the author has to select people from the Editorial Board that then select the reviewers. So as long as the Editorial Board is reasonable, the review process should be OK (note – I am on the Editorial Board although I have not been asked to do anything yet).

Do I like this system? I am not 100% sure. But I admire Eugene Koonin and colleagues for trying something different and giving the world an example of a possible way to get around the flaws of the current review system. Of course, to me, the most important thing is that the journal is Open Access, which means that anyone out there can get a fascinating look at peer review for free.

For example, people should really check out the paper and the reviewers comments and the authors responses. Or even better check out some other papers in the journal. It makes for a good read.

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This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

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Harvard Crimson changes its mind – supports PLoS One

Well, the folks at the Harvard Crimson have apparently changed their mind. In a new Editorial, two writers from the Crimson discuss PLoS One and open peer review. Unlike the previous Crimson editorial (see my blogs about it here and here), the two writers of this one now come out clearly in support of the PLoS One idea as well as some PLoS ideals.

For example, the liken the battle between Open Access and Closed Access publishing to the battle over democracy

Democracy has reached a new frontier, and we’re not talking about the Berlin Wall. It’s a new decade and a new millennium, and yet another wall is crumbling—this time, not between countries, but in the domain of scientific research.

Perhaps most importantly, they end the editorial with

Initiatives such as PLoS ONE will help promote free and unfettered scientific study, supplementing and revolutionizing an oligarchic academic process. It is both ignorant and regressive to reject this democratization.

Although they did not address the previous highly ignorant editorial in their own newspaper, Yifei Chen and Patrick Jean Baptiste deserve kudos for a well written, well thought out editorial on a key topic for the whole endeavor of science.

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This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

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World’s Smallest Genome of a Cellular Organism?

ResearchBlogging.org

A one page paper in Science reports on what I think is one of the most exciting findings in microbial genomics in years. The reports describes the sequencing and analysis of the genome of a bacterial endosymbiont of an aphid. This bacteria, known as Carsonella, has a TINY genome – only 160 kbp in length. This is ~ 3 fold smaller than the previously known smallest genome – that of Nanoarchaeum equitans which has a genome of 490 kbp.

I think almost certainly this symbiont should be considered an organelle. It is missing many cellular functions found even in the most reduced symbionts. Thus in essence it may not be the smallest genome of a cellular organism. But who cares how we define it. If it is a new organelle – that is amazing. If it is a tiny cellular genome – that is amazing too.

One thing that strikes me as strange is the fact that the paper is only one page long. It contains so little detail on what was done and what was found in the genome that the story is woefully incomplete. This I would guess is somehow related to a rush to publish but also likely due to it being published in Science, which has severe page restrictions.

This paper has been getting ENORMOUS press coverage for valid reasons. But I agree with Craig Venter (see the New Scientist article) that this genome is not of much relevance to efforts to create a “minimal” genome. This is because the ideal minimal genome is one that can support independent life. Carsonella, is far from independent and thus represents a really wild evolutionary story, but nothing of much relevance to minimal genome studies.

Some related links:

Nakabachi, A., Yamashita, A., Toh, H., Ishikawa, H., Dunbar, H., Moran, N., & Hattori, M. (2006). The 160-Kilobase Genome of the Bacterial Endosymbiont Carsonella Science, 314 (5797), 267-267 DOI: 10.1126/science.1134196

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This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

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Harvard Crimson Editorial Update

OK – so I am biased here but those interested in Open Access should check out my brother’s letter to the Harvard Crimson that was published today. He wrote it in response to the lame editorial the Crimson wrote about PLoS One. Some of my favorite quotes from his letter

They did not, however, respond to your repellent effort to rally the forces of elitism to derail a project whose primary aim is to rapidly bring scientific knowledge to everyone.

….

Once they see PLoS One, we are confident that consumers of scientific papers will discover what employers have long ago: If you’re looking for the imprimatur of greatness, try Nature or Harvard—but if you want the real thing, try PLoS One or Berkeley.

Of course, I disagree with the use of Berkeley in this context. Yes it is a public school. But come one – to use Berkeley as the “anti”elitist school of the world is a big stretch. So if you want the real thing, try U. C. Davis, not Berkeley.

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This is from the “Tree of Life Blog”
of Jonathan Eisen, an evolutionary biologist and Open Access advocate
at the University of California, Davis. For short updates, follow me on Twitter.

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