Evolution – Page 18 – Jonathan Eisen's Lab

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 |

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

M2O – Life on Mars

Scientists from NASA have reported what appears evidence that not has Mars has water in the past, but that it has flowed on the Martian surface in the last seven years. When comparing photographs of the same site in 1999 and 2005 taken by the orbiting Mars Global Surveyor, the scientists found

appearance of a lightly-shaded patch that has all the hallmarks of being caused by water bubbling up from under the Martian surface and running down the 30 degree slope

While there may be other explanations, the pictures are stunning. If this is water, I think we have to start to come to grips with the high probability that life will be found on Mars. In other words, not only might life have existed there in the past, but I think it is reasonably likely that there is life there now. Now before you get all hoity toity on me – I am not talking about little green men here. But possibly little green microbes. Or little pale microbes that use chemical energy to fix carbon and grow. Such microbes are of course all over earth, in the deep sea, in hot springs, in tidal flats, in animal guts. The real questions (again, if this is really water) the become:

could life have evolved separately on Mars?
could microbial life from Earth have seeded Mars?

I think the answers to both questions, though unclear, could potentially be yes. For question 1, if we look at the origin of life on Earth, most studies now suggest it happened over a relatively short time scale (a few hundred million years) and possibly much faster. It may in fact have been somewhat inevitable – as long as the conditions for chemical evolution were present in the Early earth. This chemical evolution could have then set up the possibility for life to have evolved. Though the exact steps are unclear for the origin of life on Earth, it is not far fetched to imagine that they could have occured on Mars as well.

As for question 2 – I think life easily could have been transported between the two planets. All you really need is for a meteorite or comet collision with Earth to blast some moderately sized pieces of material off of Earth into space. Microbes in such material could have survived for some period of time on such pieces in space (remember, many microbes do not need oxygen, and can survive incredibyl harsh conditions on Earth). Imagine if a big piece of Earth was knocked off the planet – microbes in the center of such a piece would be protected from some of the radiation and other stresses of space. And you just need one of these pieces to end up on Mars for the cross-seeding event to occur. Of sure, there are a series of assumptions here and a multiplication of low probability events. But we can make up for low probability by multiplying by 3.5 or so billion years – the amount of time that life has existed on Earth.

So this raises one final issue for me. The person with the greatest job title in the world – John Rummel, better get moving. He is the “Planetary Protection Officer” for NASA – charged with protecting other planets from Earth and Earth from other planets. One of his main jobs is to think about how to make sure the Martian missions do not bring microbes with them to Mars so that if microbes are found there we can assume they are from Mars not earth. Unfortunately in my google searches about this it seems Dr. Rummel has been promoted within NASA and I cannot figure out who took over his old job. Does that alas mean we are temporarily without a planetary protection officer? I hope not.

Whether it turns out life exists or existed on Mars or not, the finding of apparently flowing water on the surface is wildly exciting and proof to me that Mars missions are critical to our understanding of the world around us.

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.

What is that NEXTgencode Advertising on My Site

So I saw this add on my site for NextGenCode. It was very cryptic so I went to their site.

They make their site seem like they are a Biotech company promoting genetic engineering as a tool in life enhancement. But looking at their articles and other material it became clear this was a spoof of some sort. The best part of their web site are the ads, like the one for Anhedonia and the one for Losing Blondes (about blondes going extinct in 200 years). I was guessing that this was some spoof put out by people to make fun of the synthetic biology field, but then I gave in a decided to google the company.

This is when I found the Wall Street Journal article that says they are a marketing ploy for a Michael Crighton novel. (I had not clicked on the link about a book stealing trade secrets form the company, but if you do, you get a story about Crighton’s novel stealing their ideas). While some may find the slight of hand they are using here to be deceptive or malicious, I think it is pretty funny. It did not take long for me to figure out it was a spoof of some sort and it was kind of fun trying to figure it out.

Good to see that my site is being used for important advertising. Some day I will discuss the ads on my site for Intelligent Design proponents.

Here are some additional stories about Nextgencode

Nextgencode.co.UK site – Different than the .com site
Chris Abraham pooh-poohing the creativity of the Nextgencode site
Nextegencode YouTube vids
Time Magazine article
Hollywood Reporter article

Of course, any blog about Crighton would be incomplete without mentioning his scientific “credibility” or the debate about it. He has clearly written some interesting science-related books over the years and in many of them the science is not completely absurd. But his anti-global warming book, State of Fear, made Crighton seem like an anti-science advocate. Personally, I never read the book so I cannot comment about the issue directly. But here are some stories about the book for people to look at.

Neanderthals and Humans

So – we now have data and papers relating to some genome sequencing of DNA apparently from a Neanderthal fossil. I must say, even though I am a skeptic of much of the work on ancient DNA, I find the idea of sequencing the genome of a Neanderthal to be pretty cool. Perhaps more importantly than the scientific uses of this information, the sequencing is a brilliant public relations coup for genome sequencing. It is also a potentially useful tool in science and evolution education.

I will spare everyone my worries the scientific value of this work for now and am just using this post to collect links that I have found to be useful regarding Neandethal ancient DNA.

I will add more links in the next few days – or people can add them with comments

Evolution Pumpkins

Evolution fans have to check out the pumpkins at this site. I found the site by browsing around the “ClutterMuseum” blog (I was checking it out because the author poster to my blog about Davis, CA). Now, I know the FSM (Flying Spaghetti Monster) can be considered an in your face response to the intelligent design movement. But personally, the ID movement needs to be made fun of even more and the FSM is one of the best ways to do that. For more information you can read the “About” part of this blog.

Sea Urchin Genome and the Ridiculous Evolutionary Claims of Genome Researchers

All I can say is “AAAAARGH”

A sea urchin genome has been sequenced and there are some really interesting findings that have been reported based on analysis of the genome. For example, there appears to have been a large expansion of genes involved in the innate immune system in the species sequenced, Strongylocentrotus purpuratus.

All the good science aside, what most struck me were some of the ridiculous quotes attributed to some of the researchers in this project in stories and press releases. For example, in an article on MSNBC, George Weinstock says

“The sea urchin is surprisingly similar to humans,”
“Sea urchins don’t look any more like humans than fruit flies, but about 70 percent of sea urchin genes have a human counterpart whereas only about 40 percent of fruit fly genes do.”

Apparently, George was glossing over the reason this organism was chosen for sequencing in the first place. If you go to the NHGRIs web site you can get the white paper written that led to the selection of this species for sequencing. Perhaps the most important reason is that evolutionarily the sea urchin is closer to humans than fruit flies are. Therefore, it should only be a surprise to someone who does not know the evolutionary position of this species.

Perhaps even more appalling is the discussion of the apparent large number of genes for light sensory systems in this species. Again, Weinstock is quoted:

“There is not a lot of light at the bottom of the ocean, so it is not clear what they might be ‘seeing,'” Weinstock said. “This is certainly an area that will be studied intensively as a result of the genome project.”

I can only view this as some sort of joke. First of all, blind cavefish still have the genes for light perception even though they do not see. This is because it takes time for such genes to disappear. Second, apparently George has never really thought about where this species of sea urchin is found. It is found in the intertidal zone — hardly the dark depths of the ocean. I could go on and on but I will just get more annoyed. In this case, Weinstock has proven that many Genome Scientists are almost completely clueless about the organisms they are working on. Which is a shame. Becuase sea urchins are fascinating creatures and the fact that they are more closely related to humans than are most other invertebrates is one of the main reasons they have been a focus on so much research up until now. Oh well …

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.

Evolution and Politics

Scientists are acting up again. The New York Times reports that

75 science professors at Case Western Reserve University in Cleveland have signed a letter endorsing a candidate for the Ohio Board of Education.

This is great news if you ask me. Scientists seemed to be emboldened to play more of a role in politics. I think this is due to some of the recent pushes from anti-science coalitions, like the supporters of “intelligent design” as a scientific theory (which it is clearly not).

We desperately need more of this type of thing – with scientists speaking up. I do not want scientists to choose sides in truly political debates. And I hope scientists will avoid being too arrogant – such as when some suggest science can solve all the worlds woes. But when sound science is being ignored or belittled by politicians, scientists should speak up. The evolution debate is but one example. There are many more issues where sound science is being misused or ignored (e.g., global warming).

So – I recommend all scientists consider doing something to get involved. Lend your support to the folks in Ohio (e.g., Lawrence Krauss organized the group to write the letter). Or join an organization like SEFORA a new science based political action group. But just don’t sit on the side and say “scientists should not get involved.” If all scientists keep doing that, we are in deep trouble.