Misc. – Page 132 – Jonathan Eisen's Lab

Twisted Tree of Life Award: NPR on the Evolution of Crying

Well, normally I really like NPR science stories. But this one dug into my anti adaptationism feelings. Adaptationism is, in essence, the practice of saying something must be adaptive (i.e., beneficial), simply because it is there in an organism. Such cases are also referred to as “just so stories” – a play on the old Kipling “Just So Stories“. That is, in essence, people who claim something is adaptive just because it is there are in essence telling you something is this way because it is just so. I am actually not sure of the whole history of using the just-so analogy to refer to adaptationist stories – I know Stephen Jay Gould discussed this a lot in his books and lectures, but not sure who first did it.

Anyway – NPR has an adaptationistic doozy from Morning Edition:

Teary-Eyed Evolution: Crying Serves A Purpose : NPR

Basically, it seems the gist of the argument here is the following line:

Scientists who study evolution say crying probably conferred some benefit and did something to advance our species — because it’s stayed with us.

Wow – that is like straight out of the adaptationist playbook. The problem with this argument is that many things exist and persist in organisms even when they are not adaptive. There are many reasons why this can happen from constraints (e.g., if bones were not adaptive in humans it would be pretty hard to get rid of them) to invisibility to selection (e.g., some features that only show up after reproductive age may not really influence fitness) and so on.

In essence the NPR story is one of the worst examples of adaptationism in the good science press I have seen in a while. Sure this shows up all over the place. But rarely this bad at NPR. The story ends with an even worse line than the rest

Maybe that’s another reason evolution kept humans weeping: Tears help reveal the truth. And that’s because along with the tears, we’ve evolved a very sophisticated ability to interpret them.

Yes that is right. Crying has been maintained in humans because we also evolved another adaptive feature – the ability to interpret tears. So the logic here is that crying is adaptive because it is needed for another adaptive trait for which there is no evidence it is adaptive.

So for their story on crying and for in essence inventing some just so stories to explain why they think it is adaptive, NPR is the recipient of my Twisted Tree of Life Award. Previous recipients are

See also these things for some stuff on evolution of crying:

Darwin in the Crib – oldie but goodie from Carl Zimmer in 2005
Zimmer’s NY Times article related to the above.
A Critique of the Adaptationist Programme from Larry Moran at Sandwalk
My Evolution textbook has some discussion of

More (you know you wanted it) on fecal transplants and the microbiome

Image from
I Heart Guts blog

There is an interesting mini review in the Journal of Clinical Gastroenterology’s September issue that may be of interest to some out there. It is entitled “Fecal Bacteriotherapy, Fecal Transplant, and the Microbiome” by Martin Floch and well, the title is indicative of the article.

Yes, the fecal transplant meme is here to stay. Sure, the cognoscenti already knew about fecal transplants. Perhaps they had read Tara Smith’s discussion of it in her Aetiology blog in 2007. Perhaps they had pondered it when they read the article from my lab on intestinal transplants. Perhaps they had seenthis discussion on MSNBC, or various other stories out there such asthis or this post from Angry by Choice. Or, maybe you just learned about it from Bora’s Carnival of Poop.

But the meme on fecal transplants really spread and many may have first heard about fecal transplants from Carl Zimmer’s New York Times article a month or so ago “How microbes defend and define us“

In the article Zimmer discussed how Dr. Alexander Khoruts used a fecal transplant to treat a woman with a persistent and severe Clostridium infection. And Zimmer discusses how, thought such transplants had been done before, this was the first time that the microbial community was carefully surveyed before and after. (Note, my favorite part of the article is this part, where my friend Janet Jansson describes her reaction:

Two weeks after the transplant, the scientists analyzed the microbes again. Her husband’s microbes had taken over. “That community was able to function and cure her disease in a matter of days,” said Janet Jansson, a microbial ecologist at Lawrence Berkeley National Laboratory and a co-author of the paper. “I didn’t expect it to work. The project blew me away.”

Anyway Zimmer’s article, as with many of his, garnered a lot of response and got many people discussing the poop on fecal transplants.

Well, this issue of the Journal of Clinical Gastroenterology may now be the biggest pile of information about fecal transplants around. That is because, in addition to this little review mentioned above, there are in fact three articles in this issue relating to fecal transplant. Alas, most of you out there will probably only be able to read the review since the other articles are behind a pay wall.

But the review is good. And I think this is not the last you will hear about this. (Though I note that, even though I think fecal transplants have some major potential, they seem to be being oversold a bit by many as some cure all — fodder for a future “Overselling the Microbiome Award” I am sure).

I will end with this line from the review which raises some other issues about fecal transplants:

Probably one of the major problems is to define how this therapy can become socially accepted. (Can you imagine the Food & Drug Administration discussion?)

Floch, M. (2010). Fecal Bacteriotherapy, Fecal Transplant, and the Microbiome Journal of Clinical Gastroenterology, 44 (8), 529-530 DOI: 10.1097/MCG.0b013e3181e1d6e2

Grehan, M., Borody, T., Leis, S., Campbell, J., Mitchell, H., & Wettstein, A. (2010). Durable Alteration of the Colonic Microbiota by the Administration of Donor Fecal Flora Journal of Clinical Gastroenterology, 44 (8), 551-561 DOI: 10.1097/MCG.0b013e3181e5d06b

Khoruts, A., Dicksved, J., Jansson, J., & Sadowsky, M. (2009). Changes in the Composition of the Human Fecal Microbiome After Bacteriotherapy for Recurrent Clostridium Difficile-associated Diarrhea Journal of Clinical Gastroenterology DOI: 10.1097/MCG.0b013e3181c87e02

Yoon, S., & Brandt, L. (2010). Treatment of Refractory/Recurrent C. difficile-associated Disease by Donated Stool Transplanted Via Colonoscopy Journal of Clinical Gastroenterology, 44 (8), 562-566 DOI: 10.1097/MCG.0b013e3181dac035

Overselling the microbiome award: Stephen Barrie on pre and probiotics at the Huffington Post

Yes, I think the microbes that live in and on people are important, interesting, cool, and worthy of lots and lots of attention. However, I am getting sicker and sicker of the ways in which the effects of these microbes are, well oversold. So today I am starting a new series here on the Tree of Life – the “Overselling the Microbiome and Probiotics Award.”

And, we have a winner today. The winner is Stephen Barrie who has posted something at the paragon of high quality science – the Huffington Post (for more on the dubious science at Huffington Post, a good place to look is Bora’s Blog Around the Clock). Well, Barrie really takes the cake on this one

Stephen Barrie, ND: The Keys to Maintaining a Healthy Gut

He starts off OK – referring to the number of microbes in the human ecosystem and even quoting Jeroen Raes, who does some great work.

Then he mentions how

“These bacteria have a profound influence on human physiology, your immune system, your nutrition, and are crucial for human life.”

OK I can go with this — maybe an exaggeration but still within reasonable confines. Then the woppers begin

“The health of your body and mind is largely tied to the health of your gut”.

Wow- that is one serious jump – from these microbes have a profound influence to the gut driving health of body and MIND.

Then he goes back to some OK territory again, discussing some functions known for gut microbes, like vitamin production, preventing infection, etc. But just after this he switches to the woppers again claiming that out of balance microbes can cause allergies, inflammatory bowel disease, eczema, arthritis, irritable bowel disease, obesity, autism and personality changes including paranoia, hostility, aggression and so on. Completely ludicrous actually. What we know about these issues is that researchers have found that microbial populations may be altered in people with these maladies. But that does not mean the alteration in the microbes caused these maladies. It could be that other factors cause both the malady and the microbial alteration or the malady itself could lead to altered microbial populations.

But wait, it gets a bit better. Now that he has established that microbes cause all these problems, he tells us how to

“avoid one of the emerging causes of both obesity and food allergies? Lower your risk of inflammatory bowel disease, irritable bowel disease, eczema, colon cancer (15) strengthen your immune system? All this while reducing any levels of paranoia or hostility (and retaining your Jon Stewart sense of humor).”

The recipe for prevention is as follows:

Eat a low fat diet rich in vegetables, fruits and complex carbohydrates

Limit consumption of animal protein

Reduce sugar consumption

Increase pre-biotic and probiotic intake

Consume enough soluble and insoluble fiber to maintain a daily bowel movement. A slow bowel transit time leads to increased exposure of your body to toxic bowel contents.

Reduce dietary sulfate consumption.

Again, I am all for more research into the microbiome. And I think microbes that live with us must have all sorts of positive and negative effects on our health. And yes, I understand why “probiotics” and “prebiotics” are getting lots of hype. But because Barrie has gone from what must be a gut feeling (sorry) to making medical claims without evidence and prescribing treatments to cure ailments that probably don’t exist, he is the recipient of my first “Overselling the microbiome award”.

Quick blog post: interesting piece on the evolution of ecology by Simon Levin

There is a very interesting piece in the Chronicle of Higher Education by Simon Levin on the “Evolution of Ecology.”

See The Evolution of Ecology – The Chronicle Review – The Chronicle of Higher Education

In it Simon, who I consider both a friend and colleague and who has been an inspiration to me for much of my work, discusses the history of the concept and the field of ecology. He repeats a key phrase he has used elsewhere:

Ecology, the unifying science in integrating knowledge of life on our planet, has become the essential science in learning how to preserve it.

I like this phrase and plan to use it a bit here and there, with attribution of course.

Levin also discusses how Darwin’s Voyage of the Beagle helped launch the field of ecology because it

defined a new and synthetic way of looking at nature—in which the patterns characteristic of particular regions found explanation in a unifying, dynamic framework

It was only after Voyage of the Beagle and Wallace’s work and others that the term “oekologie” came into being.

I particularly like the end where he connects ecology to study of other complex adaptive systems like economic ones and medical ones.

The article is really really really worth a read.

Lack of neutrality in bacteria and where pseudogenes go when they die

Pseudogenes, which are in essence regions of the genome that used to be genes but no longer able to produce a functional unit, have long been considered to be models of the genetic equivalent of Switzerland’s neutrality. With this assumption of neutrality in hand, researchers have used studies of pseudogenes to better understand what happens to DNA when it is not visible to any form of natural selection. That is, pseudogenes have been thought to be neither harmful (as in, they are not under negative selection) or helpful (i.e., they are not under positive selection).

And from this assumption we have supposedly learned about mutation rates and patterns (because if they are neutral then the changes in pseudogenes should be reflective of mutational processes, not selection) as well as all sorts of other features of genome evolution.

Over the years, some have challenged the assumption of neutrality of pseudogenes (e.g., see here) like many have questioned whether Switzerland is really neutral. But overall, the feeling that pseudogenes were mostly neutral seems to have stuck. However, that may change a bit with a new paper from Chih-Horng Chu and Howard Ochman in PLoS Genetics (PLoS Genetics: The Extinction Dynamics of Bacterial Pseudogenes).

In their paper they report: (this is their authors summary)

Pseudogenes have traditionally been viewed as evolving in a strictly neutral manner. In bacteria, however, pseudogenes are deleted rapidly from genomes, suggesting that their presence is somehow deleterious. The distribution of pseudogenes among sequenced strains of Salmonella indicates that removal of many of these apparently functionless regions is attributable to their deleterious effects in cell fitness, suggesting that a sizeable fraction of pseudogenes are under selection.

Basically, what they did was the following

1. Compare Salmonella genomes. Identify putative pseudogenes and trace their evolution onto a phylogeny of the species.

Figure 1. Distribution of pseudogenes among Salmonellagenomes.

The phylogenetic tree was inferred from 2,898 single-copy genes shared by all fiveS. enterica subsp. enterica strains and the outgroup S. enterica subsp. arizonae.

doi:10.1371/journal.pgen.1001050.g001

2. Carry out a variety of analyses of the pseudogenes such as

looking at ratios of Ka/Ks (this is in essence a ratio of amino acid changes – aka non synonymous substitutions to “silent” synonymous changes which occur when the DNA sequence changes but the same amino acid is encoded).
examining the types and frequencies of gene inactivating mutations

3. Then they looked at the “ages” of pseudogenes – with age being estimated by the position in the tree in which the pseudogenes appear to have arise.

4. Finally the examined the age class distribution of pseudogenes as well as whether there were other differences between pseudogenes of different ages. And what they found was inconsistent with a neutral model. Instead, what they conclude is that something is making it advantageous to delete pseudogenes more rapidly than one might expect.

What explains this? After testing multiple possibilities the authors conclude that their is some negative selection against pseudogenes (or I guess positive selection for deletion of pseudogenes).

They conclude by suggesting this is likely to be pervasive across all bacteria and even in archaea. And furthermore make a connection to possible selection on intron size in eukaryotes. Anyway – the paper seems quite interesting and worth a read. Still pondering what it all means, so I would welcome comments.

Kuo, C., & Ochman, H. (2010). The Extinction Dynamics of Bacterial Pseudogenes PLoS Genetics, 6 (8) DOI: 10.1371/journal.pgen.1001050

Human genome project oversold? sure but lets not undersell basic science

Well, the piling on the human genome project continues, it seems at an accelerating pace. I think most of this comes from the fact that we are in the range of the 10 year anniversary right now. Here are some examples of recent stories suggesting the human genome project (or projects, if you count the public effort and Craig Venter’s effort as separate) have had little benefit:

7/31/10: The Human Genome Project: 10 Years Later, Progress but Still a Puzzle – WNYC. Interesting piece by Sarah Kate Kramer discussing the limited clinical value of the HGP. Includes some criticisms of personalized genomic medicine.
7/29/10: Spiegel interview with Craig Venter with the headline “We have learned nothing from the genome”. Has lots of interesting tidbits. Love the Venter line “Well, nobody likes to be beaten — by superior intelligence, planning and technology. That gets people upset.” But I note Craig emphasizes the basic science value of human genome data.
7/6/10: Public Radio mini story about Mike Mandel’s article on the failure of the human genome project.
6/12/10: Nick Wade’s NY Times article on “A decade later, genetic map yields few new cures“. In this Wade discusses many of the issues with both the sequencing of the human genome and some of the spinoff projects (and also butchers some evolutionary biology for which I gave him a twisted tree of life award).

These are but a small sampling of the many many blogs, articles, and other reports that either directly state or suggest that much of the money spent on the human genome project was a waste.

Certainly, contrary to the suggestion of some of these articles, there have been some practical benefits that have come directly or indirectly from human genome sequencing. But equally certainly, these critiques have a segment of truth to them in that the practical benefits have been few and far between.

Normally, one would not expect too many direct practical benefit to come from this kind of science project. But alas, the problem here is that many of the key players (e.g., Eric Lander, Francis Collins, Craig Venter) in the sequencing of the human genome(s) oversold the potential benefits that could come from the sequencing. In a way, it was their job to oversell the sequencing, since each was a cheerleader in ways for getting others to do a lot of work.

Many people knew at the time that this overselling was going on. It was talked about extensively at various genome conferences and even occasionally in the press and scientific literature (boy do I wish I had had a blog then, because I was one of those people at conferences practically begging people to not oversell the benefits of the project – I now even give out an “overselling genomics award” on my blog ). The cautionary voices were mainly saying that there was no need to oversell the project and that we should stick to the benefits of “knowing” ourselves and not guess about how it will lead to immediate cures for diseases. And many said “If you oversell this now, it will come back to bite you“

And thus it is not surprising to me that there is somewhat of a backlash now. But there is a very dark side to the backlash that has potential to hurt science for many years to come. If there is a need in the future for large scale science / medical projects, I can guarantee that some critics will step up and say things like “Well the war on cancer failed. And the human genome project failed. Why should we trust you now?”

The problem here is that the human genome project should never have been sold as a means to a series of practical ends. It should have been sold as a massive basic science project, much like going to the moon or building a giant linear accelerator. That is, the human genome project was, and still really is, about knowledge. It is about knowing ourselves. It has enormous potential benefits in all sorts of areas, like human medicine. It should greatly aid and abet studies of human biology and genetics and disease. But given that benefits that come from such studies are impossible to predict, the human genome project should have been presented in a different way. We need to discuss more in public why basic science is important even if one cannot predict what the benefits are.

In many ways, this is very much like the “war on cancer” which some have argued failed because we still have cancer killing a lot of people. But this is off base because in fact the war on cancer has provided us with an incredible baseline of information about the biology of cancer. We need to do a better job in all of these cases of defending the need for knowledge, and discussing how fighting cancer and curing diseases is not the same as building a big bridge or road.

The best person discussing this issue for the last ten or so years in my opinion has been Harold Varmus, who was once the head of NIH and is now the new director of the National Cancer Institute. I have heard him repeatedly defending the “war on cancer” in terms of its basic science benefits. For example see his comments on Science Friday 1/30/2009 and 7/16/2010. There just have not been too many people doing a good job of this with genomics. Venter and Collins have been OK here and there. But we need more.

On a related note, we probably should have more discussion about how the money spent on the genome project and the war on cancer pales in comparison to money we spend on other things (e.g., interest on the national dept, wars, etc) but perhaps that is a side discussion.

Most importantly, we need to bring out to the public more of a discussion of the benefits from basic science. Here are some useful resources if you want to try and help:

I also encourage people to look at the National Academy of Sciences report A New Biology for the 21st Century: Ensuring the United States Leads the Coming Biology Revolution. I note, I was one of the coauthors. You can download the PDF of the whole document after giving your email address.

I am going to start a new series here on this blog called “Benefits of basic science” where I will be discussing these issues. I encourage others out there to also bring more to the forefront discussions of the need for basic science.

——————–
UPDATE

Also see

Twisted tree of life award #6: Scientific American Origins piece for dissing microbes

There is an interesting series of mini articles in the August 2010 Scientific American tracing the origins of various concepts and things: Origins: Going Back to Where the Story Really Starts: Scientific American

Not open access mind you, but if you have a subscription it is worth checking out. They track the origins of the following:

swiss cheese
paternal child care
computer viruses
animation
sexual reproduction
malaria
fireworks
barbed wire
hand washing in hospitals
human morality
electric cars
the influenza virus
wheeled vehicles
black holes
zero
biodiversity
noodles

Many of the discussions are interesting. Some are a bit trite. But that is not what I am here to report on. I am here to complain about one aspects of the article series: too much emphasis on humans and multicellular organisms as “higher” creatures. There are various subtle phrases here and there that I did not like too much but the parts that really grate on me are the two below:

In the article on biodiversity Melinda Moyer discusses the remarkable possibility that single celled creatures might have in fact had some diversity in them “Today we think of biodiversity in terms of multicellular life, but flowering plants and animals didn’t arrive until relatively recently” she writes. And ends with “It is no comfort to know that the worst catastrophe would still preserve some biodiversity — even if only for the lowly cell.“
In the mini article on sex, Brendan Borrell writes “The truth is, nobody really knows why people — and other animals, plants and fungi — prefer sex to, say, budding.” This of course leaves out all the other eukaryotes that are not plants, animals and fungi that have sex.

And though these are certainly subtle small issues, I feel that Scientific American should do better. So for directly and indirectly dissing the microbes on the planet – I am giving them my coveted Twisted Tree of Life Award #6. Previous winners are listed below:

Testing, testing – why we need more testing like this in genomic informatics & annotation methods

Just got an announcement regarding this challenge:

Automated Function Prediction SIG 2011 featuring the CAFA Challenge: Critical Assessment of Function Annotations | Automated Function Prediction 2011 July 15-16 2011, Vienna, Austria

Here is a description:

CAFA is a community-driven effort. We call upon computational function prediction groups to predict the function of a set of proteins whose true function is sequestered. At the meeting, we will reveal the functions, and discuss the predictions. The CAFA challenge goals are to foster a discussion between annotators, predictors and experimentalists about methodology as quality of functional predictions, as well as the methodology of assessing those predictions. Registration for CAFA starts July 15, 2010 and the CAFA challenge will take place September 15, 2010 through January 15, 2011.See here for more details on how you can enroll in CAFA.

This is near and dear to my heart as I have been working on methods to predict gene function from sequence for some 15 years now. My first paper on this was in 1995 in which I showed that for genes in multigene families, phylogenetic trees of the gene family could help in predicting functions of uncharacterized members of the gene family. More specifically, I suggested that the position of an uncharacterized gene in a gene tree relative to characterized genes could be used to predict its function. I did this for one family in particular – the SNF2 family – but argued that it could be applied to other families. (I think perhaps it was the first time someone had made this specific argument about using trees to predict function, but am not sure)

I then formalized this idea with a few papers (e.g., here and here) describing a “phylogenomic” approach to predicting function (alas, this is when I invented my first omics word). And for many years since, I continued to work on functional prediction methods and continue to do so. When I was at TIGR for eight years I did this both in my own research and helped others with their functional predictions. I firmly believe that evolutionary ~~approached~~ approaches are critical in such functional prediction and have laid this out in a series of talks and papers (e.g., see this more recent one).

Anyway, enough about me. I can argue all I want about how brilliant I am and about how evolutionary methods are the best approach. But arguing is alas not science. What we need are tests and experiments. And that is where things like CAFA come in. In CAFA one can test how well various functional prediction methods work. And the people involved in CAFA (including organizers Iddo Friedberg, Michal Linial, and Predrag Radivojac and others such as Amos Bairoch, Sean Mooney, Patricia Babbitt, Steven Brenner, Christine Orengo and Burkhard ~~Rosh~~Rost)) are to be commended for putting this together because we do not have a lot of these activities and need more in all aspects of genomics (and metagenomics too). Others have discussed doing tests of functional prediction methods before, but I am not sure if any have happened per se.

Have a favorite functional prediction method? Enter it in the competition or give a talk on it. And if you are feeling inspired, organize a similar activity in your area of science – testing is a good thing.

See also Iddo Friedberg’s post about this

What is not getting any love at this #metagenomics meeting

Well, Here I am for day 2 in Snowbird at a meeting/workshop discussing the potential for “Terrabase metagenomics”. The main point of the meeting is to discuss whether there would be value in massive massive Metagenomic sequencing in one way or another. I note I have enjoyed this meeting so far greatly – nice and small with some really good people.

Yesterday i gave a talk on microbial evolution and a few others talked about other topics (Rob Knight talked about microbiomes, Jeroen Raes discussed multiple Metagenomic projects, and Rachel Mackelprang discussed permafrost metagenomics). I will write more i hope soon about the science side of this meeting. But that is not what I am here to write about today. I am going to tell you what topics were not getting any love so far at this meetings. And this is not a completely snarky thing here – what people complain about does give some feel for what people are thinking about. In no particular order, here are some examples.

The human microbiome project (well, some parts of it)
The CAMERA metagenomics DB (significant disappointment in their progress )
NCBI (or specifically the short read archive)
Bureaucracy (and how it impedes science)
Lack of support for informatics
Lack of air (we are at 8000+ feet)
Large meetings
Jet lag
IRBs
Lack of RAM (many Metagenomic analyses require massive amounts RAM)
Bad alcohol (as in drinks)
Plants and animals (this is a meeting focusing on microbes)
Lack of cooperation among funding agencies
Pathogens (most people here are interested in either human commensals or environmental organisms)
Difficulty in founding joint projects between US and Europe
Projects that don’t collect metadata
Software tools that don’t work with each other

CA scientists – time to rally for a good rock (serpentine)

I have been spending much more time on Twitter recently than on my blog, though I am trying to get back into the blog more and more. And today I am posting a mini post here that is more like a twitter post but I just have to at least put this on the blog. Sheril Keirshenbaum is calling for all Californians to DO SOMETHING in regard to this inane attempt to remove serpentine as the State Rock of California. See here recent post here:

Calling on Californians: West Coast Represent! | The Intersection | Discover Magazine

Really not much more to say than she has said, but I call on everyone in CA to do something about this.

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