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December 28, 2010

How "mostly harmless" bacteria manipulate the immune system

"It may be better to keep alive the goose that lays the golden eggs than to kill it. But this argument depends on the assumption that, if you do not kill the golden goose, no one else will either: that is, it assumes that the host is infected by a single clone of symbionts." -- Maynard Smith 1989 Nature 341:284-285.

This week, I'll discuss a paper recently published in Science: Has the Microbiota Played a Critical Role in the Evolution of the Adaptive Immune System?, by Yun Kyung Lee and Sarkis K. Mazmanian. They argue that gut bacteria produce "signals that are recognized by host receptors to mediate beneficial outcomes for both microbes and humans."

Well, how nice! What sort of outcomes would be beneficial for a gut microbe? Reproducing a lot in the gut and spreading to lots of new hosts would be good. How to do this? Diarrhea seems promising. That might sicken or even kill the human, but does that matter to the microbes? Paul Ewald has pointed out that pathogens whose spread depends on host mobility may evolve lower virulence, so people with the flu feel well enough to go to work and spread it. Pathogens that spread via sewage to drinking water, though, may spread more readily if they cause more severe diarrhea. But we also need to consider conflicts of interest among gut bacteria, not just conflicts of interest with the host. For example, species X might trigger diarrhea before species Y has had time to reproduce much. If so, then species Y might benefit from suppressing, or at least delaying diarrhea.

More generally, the diversity of bacteria in the gut creates a "tragedy of the commons", where bacterial strains that pursue their own interests would rapidly out-compete hypothetical strains that sacrificed their own interests for the "greater good", either of the host or of the entire gut bacterial community.

Or so I would predict. But what about those mutually beneficial "signals?"

According to the paper, some bacteria produce a molecule called PSA, which suppresses inflammatory gut defenses. An overactive immune response in the gut leads to colitis, so suppressing inflammation can benefit humans. But is that why some bacteria have evolved to produce PSA? It's more likely that individual bacterial cells (or clusters of clonally identical bacterial cells) benefit by suppressing inflammatory responses in their own immediate neighborhood. Any overall benefit to the host (or to other gut bacteria) is merely a side-effect. If so, then I would call this "manipulation" of the host, rather than a "signal." In areas where dangerous gut infections are rare, this down-regulation of the immune response would usually be beneficial, but perhaps not always.

Segmented filamentous bacteria (SFBs), also discussed in the paper, have almost the opposite effect from PSA-producers. SFBs stimulate differentiation of certain T cells, specifically TH17 cells. These help protect against pathogens, usually without causing colitis. But

"microbes that stimulate T helper cell development may (inadvertently) also increase the inherent immune reactivity of the host, potentially leading to host-destructive pathologies"

I guess we can't blame the bacteria, if they didn't mean to cause disease. So, what's the "signal?" Possibly ATP, according to the paper. But is ATP a "signal", benefiting both sender and receiver? Or is it a "cue", released inadvertently, perhaps by dying bacteria, and providing information useful to the receiver, in this case, the host?

To qualify as a signal, ATP would have to be actively released by SFBs. Furthermore, SFBs that release ATP would have to have greater fitness in the gut than mutants that don't release ATP. If both of these are true -- neither has been shown, as far as I can tell -- then ATP could be either a signal (if the host consistently benefits) or a form of manipulation, if the SFBs benefit consistently but the host only benefits haphazardly, if at all. Calling any information-bearing molecule a "signal" obscures the key issue of how transmission of that information affects the fitness of senders and receivers.

December 23, 2010

This week's picks

Papers I'm considering this week:

Relatedness influences signal reliability in evolving robots

Conditions for mutation-order speciation

The evolution of punishment through reputation

Grandmothering and natural selection

Horizontal acquisition of multiple mitochondrial genes from a parasitic plant followed by gene conversion with host mitochondrial genes

Brothers delay menarche and the onset of sexual activity in their sisters

How the vertebrates were made: selective pruning of a double-duplicated genome

Defining individual quality over lifetimes and selective contexts

Genetic and 'cultural' similarity in wild chimpanzees

Has the Microbiota Played a Critical Role in the Evolution of the Adaptive Immune System?

How the insect immune system interacts with an obligate symbiotic bacterium

December 22, 2010

Our secret is out !

Fort_Denison.jpgFor millennia, we Denisovans have hidden in our secret fortress laboratories, underground in Siberia and out at sea, like Fort Denison, occasionally interbreeding with humans from neighboring islands. We didn't expect you to discover the traces of the latter activity so soon. Looks like we'll have to use our interstellar spaceship earlier than planned. So long, and thanks for all the fish!

December 15, 2010

One evolutionary biology lab's publications in one year match "intelligent design's" 5-year total

In one of my first posts, I surveyed the scientific literature and found that there are thousands of scientific papers published on evolution every year, strong evidence against the long-running claims of evolution-denialists that scientists are rejecting evolution. But would it be rude to compare a single evolutionary biology lab's research productivity for one year to "intelligent design's" total for five years?

Denison lab: 4 papers published in 2010, all with original data.
They claim: 0 in 2010 (as of today), 2 in 2009, 0 in 2008, 0 in 2007, 2 in 2006...
... so 4 papers in 5 years (<1/yr), 0 with original data.

Their pathetic publication record confirms the criticism their list was intended to refute, namely, that intelligent design advocates don't publish much because they "don't have scientific data." Here's our list:


4) Ratcliff, W.C., R.F. Denison. 2010. Individual-level bet hedging in the bacterium Sinorhizobium meliloti. Current Biology 20:1740-1744.
Perhaps because the duration of starvation is often unpredictable, these bacteria "hedge their bets" by dividing into one starvation-resistant "persister" and one more-active "grower." See this blog post.

3) Oono,R., R.F. Denison. 2010. Comparing symbiotic efficiency between swollen versus nonswollen rhizobial bacteroids. Plant Physiol. 154:1541-1548.
Rhizobia provide nitrogen more efficiently (more N per CO2 respired) in hosts that make the nitrogen-fixing bacteroid form swell up and lose the ability to reproduce, relative to the same rhizobial strains in hosts where bacteroids aren't swollen. See this blog post.

2) Denison, R.F., J.M. Fedders, B.L. Harter. 2010. Individual fitness versus whole-crop photosynthesis: solar tracking tradeoffs in alfalfa. Evolutionary Applications 3:466-472. By disrupting solar tracking and measuring effects on photosynthesis, we showed that the overall effects of tracking on photosynthesis can be negative. So why do they do it? See this blog post.

1) Oono,R., I. Schmitt, J.I. Sprent, and R.F. Denison. 2010. Multiple evolutionary origins of legume traits leading to extreme rhizobial differentiation. New Phytologist 187:508-520.
Legumes have evolved the ability to impose bacteroid swelling (shown above to increase nitrogen-fixation efficiency) repeatedly. See this blog post.

Our small lab should outperform all of "intelligent design" again in 2011, as the following have been already published or accepted:

Denison, R.F. 2011. Past evolutionary tradeoffs represent opportunities for crop genetic improvement and increased human lifespan. Evolutionary Applications (already on-line). See this post.

Kiers, E.T., R.F. Denison, A. Kawakita, E.A. Herre. 2011. The biological reality of host sanctions and partner fidelity. 2011. Proc. National Academy of Sciences (already on-line). Four of us, each studying a different mutualism, critique this paper, one of many that draws incorrect conclusions from modeling that ignores the tragedy-of-the-commons created by multiple symbionts per host, as I've discussed previously. Here's their response.

Oono, R., C.G. Anderson, R.F. Denison. 2011. Failure to fix nitrogen (N2) by nonreproductive symbiotic rhizobia triggers host sanctions that reduce fitness of their reproductive clonemates. Proc. Roy. Soc. B (already on-line). Inside the root nodules of some legume species, rhizobial bacteroids (the differentiated form of these bacteria, which convert atmospheric nitrogen into a form the plant can use) have lost the ability to reproduce. If these plants just cut off resources to nonreproductive bacteroids that fixed too little nitrogen, that would have no direct effect on future generations of rhizobia. But Ryoko Oono and Carolyn Anderson showed that pea and alfalfa, two examples of such legumes, can reduce the reproduction of the bacteroids' still-reproductive clonemates in the same nodule, perhaps by cutting off resources to an entire nodule when it doesn't fix nitrogen.

Ratcliff,W.C., R.F. Denison. 2011. Bacterial persistence and bet hedging in Sinorhizobium meliloti. Communicative and Integrative Biology (abstract already on-line). This is a follow-up to Will Ratcliff's recent paper showing that starving rhizobial bacteria bet-hedge by splitting into one high-resource "persister" (which can survive long-term starvation) and one low-resource but more-active "grower." New data in this paper show that the persister cells are resistant to an antibiotic that kills growing cells, and that they have lower rates of protein synthesis, at least for the green-fluorescent protein.

Hendry, A.P., M.T. Kinnison, M. Heino, T. Day, T.B. Smith, G. Fitt, C.T. Bergstrom, J. Oakeshott, P.S. Jørgensen, M.P. Zalucki, G. Gilchrist, S. Southerton, A. Sih, S. Strauss, R.F.Denison, and S.P. Carroll. 2011. Evolutionary principles and their practical application. Evolutionary Applications (in press). What can evolutionary biology contribute to conservation biology, agriculture, and medicine? This synthesis paper from the Applied Evolution Summit, held on Heron Island in January finds some useful generalizations.

My research has been and is supported by the National Science Foundation, but the opinions expressed here are my own.

December 12, 2010

Conditional cooperation and forest management

A while ago, I asked readers which of several papers they would most like me to discuss. The only request was for a paper which, though related to my own interests in the evolution of cooperation, isn't exactly evolutionary biology, "Conditional cooperation and costly monitoring explain success in forest commons management". I decided to discuss it anyway. Anyone particularly interested in the tragedy of the commons might also find some older posts in my moribund blog, The Comedy of the Trojans, worth reading.


"To many, the word coercion implies arbitrary decisions of distant and irresponsible bureaucrats; but this is not a necessary part of its meaning. The only kind of coercion I recommend is mutual coercion, mutually agreed upon by the majority of the people affected." -- Garrett Hardin, The Tragedy of the Commons

Garrett Hardin's "The tragedy of the commons", published 42 years ago in Science, is one of the most influential papers of all time. He made four main points, of which the first two have received the most attention:
1) Some important problems cannot be solved by purely technological means. For example, increasing crop yields is at best a temporary solution to the problem of feeding an ever-growing population.
2) Adam Smith's "invisible hand", whereby individuals following their own interests benefit society as a whole, doesn't always work. This is because the individual benefit from grazing a cow on shared land (a "commons"), or from harvesting a rare fish species, or from a manufacturing process that pollutes the air, can exceed the individual cost of that one cow's damage to the grazing land, the slightly increased extinction risk for the fish species, or breathing slightly more-polluted air.
3) Human decisions about reproduction are similar to the above examples, because they are largely based on individual costs and benefits. Any genetic or cultural lineages that restrain their reproduction for the public good will be overwhelmed by lineages that do not.
4) It is widely recognized that some limitations on grazing, fishing, and pollution are needed to bring individual behavior in line with the long-term common good. Similarly, some restriction of the freedom to breed will be necessary to limit population growth.

Except in China, which apparently missed the "mutually agreed upon" part, most people have ignored Hardin's main point, the claim that some form of mutual coercion is needed to limit human reproduction. Instead Elinor Ostrom and others have done lots of good research on the ways that various groups manage common resources, such as forests or fishing grounds. When she spoke here recently, by video link, I was surprised to hear her accuse Hardin of advocating government (as opposed to community) control of common resources. I'm sure he advocated government control in some cases, but his statement quoted above is equally consistent with community-based solutions. The key point is that there must be some individual incentives for individuals to act in ways consistent with the common good.

An example of recent work on commons management is a paper, also published in Science, titled "Conditional cooperation and costly monitoring explain success in forest commons management", by Devesh Rustagi, Stefanie Engel, and Michael Kosfield. They compared 49 different community groups in Ethiopia, each of which manages a forest. In the absence of some mechanism to prevent individuals from, for example, harvesting too many trees, Hardin's hypothesis would predict over-harvesting and deterioration of the common resource.

The researchers used the number of young trees per hectare (PCT=potential crop trees) as a measure of management success. Most such trees were cut for charcoal before the community-management program began, so regrowth of young trees requires communities to forgo some immediate gain for longer-term benefits.

The abstract of the paper reports that this measure of successful management was correlated with "conditional cooperation." This seemed a bit odd to me. In a group of only two people, it's simple enough to say "I won't over-harvest if you don't", but that sort of tit-for-tat cooperation doesn't directly translate into larger groups. It turns out, though, that the authors measured conditional cooperation using a two-person version of the public goods game, where conditional cooperation essentially amounted to punishing non-cooperation by the other player. That attitude (or cultural norm) seems likely to translate into some tendency to enforce forest-management rules in the real world. And indeed, individuals classified as conditional cooperators based on the game spent more time patrolling the forest, enforcing rules against over-harvesting.

What about the "community" versus "government" distinction? Is the "executive committee on the group level chaired by the group leader" charged with "punishment of free riders" part of a community, a form of local government, or both? In any case, the "distant bureaucrats" apparently disdained by both Ostrom and Hardin do play at least two key roles. The article states that:

"...groups of the Bale Oromo people were given secure tenure rights to use and manage their forests as common property resources (39). In return, these groups are required to maintain their forest cover, for which they are allowed to implement local rules regarding forest use"

So the national or regional government (1) protected group land tenure (for example, against the sort of problem Ostrom mentioned in her talk here, where a local community managing their fishery sustainably was unable to exclude outsiders who over-harvested), and (2) enforced result-based management standards, though without micromanaging. For example:
"...assessment is carried out once every five years by the forest administration with active participation from group members. The main purpose of this assessment is to determine the annual allowable timber quota and the rent each group has to pay to the local forest administration".

December 10, 2010

Scientific tourism?

I'm adding a new category of posts: "science tourism." This includes traveling for ecotourism or to visit science museums. Volunteering to help on a research project (perhaps through Earthwatch) or going to a scientific meeting (particularly one outside one's own specialty, if you're a scientist) are also science tourism.

Here are a few examples of science tourism (or scientific tourism) I've enjoyed.

Musée des Arts et Métiers, Paris. I was in Paris to speak to a meeting of plant breeders focused on organic farming. The museum includes Focault's original pendulum and is a major setting for Umberto Eco's book by that name. But it also includes Focault's less-known demonstration of the earth's rotation: a gyroscope with a microscope to detect the tiny apparent shift in its plane of rotation during its 10-minute spin time, as the earth turns around it. Also an example of the pre-Morse shutter-based "telegraphs" mentioned in The Count of Monte Cristo, looms controlled by player-piano-like paper rolls, a hand-cranked machine for making metal files, the apparatus Lavosier used to weigh hydrogen and oxygen before combining them into water, etc. My wife and I ended up spending all day there.

Heron Island, on the Great Barrier Reef. I was there for the Applied Evolution Summit, but got to snorkel on the reef during afternoon breaks. I wrote about this already and linked to a video that summarizes some themes from the meeting but also includes lots of nice wildlife shots. I'm guessing the resort on the island is quite expensive, but the food there is good. I stayed at the research station, which is mentioned in Arthur C. Clarke's The Deep Range.

Tech Museum in San Jose, California. I was in town for the Ecological Society of America meetings, in 2007. They had a hands-on lab exercise to transform bacteria, adding a gene that made them fluorescent. I just followed the instructions ("first, take the rack of red tubes out of the refrigerator"), which ended with putting a plate of transformed bacteria in an incubator. Some staff person took the plates out after the bacteria grew up, then put pictures up on the web, so you could see if the transformation worked.

What's your favorite destination for science tourism?