This Week in Evolution

Experimental evolution meets genomics

2009-11-05T21:37:57Z

Richard Lenski and colleagues have been monitoring evolution of the bacterium Escherichia coli in his laboratory for 40,000 generations. Their latest paper, "Genome evolution and adaptation in a long-term experiment with Escherichia coli" was recently published in Nature.

One nice thing about E. coli is that they can freeze samples of their evolving populations every few thousand generations, for later analysis. So they were able to compare the fitness of different generations by competing each against a thawed ancestor. They also found the complete DNA sequence for many of these strains....

]]> This wouldn't have been possible when their evolution experiment began. It would have been impossibly expensive even a few years ago, but DNA sequencing has been getting cheaper, as Richard Dawkins predicted in his essay, "Son of Moore's Law."

They found that their bacterial populations accumulated genetic changes at a fairly constant rate over the first 20,000 generations. This is what you would expect, if they were randomly accumulating "neutral" mutations, with no effect on fitness. But random neutral mutations would include "synonymous" mutations that change DNA sequence without changing the corresponding protein, whereas they found mostly protein-changing mutations. Those should have some real effect and apparently a positive one.

Over the same period, fitness increased relative to the ancestral strain. But the increase in fitness showed a different pattern from total changes in DNA sequence. While DNA sequence changes accumulated at a fairly constant rate, fitness increased very rapidly over the first 1000 generations or so. Since then, fitness has continued to increase, but much more slowly. This later increase could be roughly linear, but there's enough noise in their data that it's hard to be sure. One possible explanation for this pattern is that the early genetic changes had wide-ranging effects, even if the DNA-level changes were small. This is what you would expect if the changes involved regulatory systems, for example. Those early changes were clearly positive, on balance, but they may have had some negative side effects. The slow-but-steady improvements since then may involve a large number of genes, each with a small beneficial effect, possibly reducing some of those negative side-effects.

Fellow microbial evolutionary biologist Paul Rainey has a commentary on the paper in the same issue. Rainey himself has published a very interesting paper even more recently, which Will Ratcliff has promised to write about.

Experimental evolution of sex (revised)

2009-10-23T18:29:31Z

"I show that a similar cost of sex exists when asexual mutants arise... but not when the species is a self-fertile hermaphrodite.... Although individual fitness (expected reproductive success) is assumed to be equal for sexual and asexual females, the heritability of fitness is... twice as high in asexual females" -- Richard Michod, Darwinian Dynamics

I should be working on my book, but a paper that just came out in Nature got me thinking about sex. A population with half males and half females will grow only half as fast as one consisting only of females that self-fertilize or clone themselves. So, many people have asked why sex evolved.

That's an interesting question, but I'm not sure about the rationale. As noted by Michod, a population of self-fertilizing hermaphrodites doesn't have any intrinsic growth advantage over a population of hermaphrodites that mostly cross-fertilizes. So is the problem sex, or males?

Evolutionary changes in gene frequency over generations depend on whether individuals with a given gene survive and reproduce more than other members of their population, not on the consequences for overall population growth. (Individuals can move between populations.) So we really have two related questions:
1) why do genes for producing male offspring persist? and
2) why do genes for cross-fertilization persist in species that can self-fertilize?

From an individual perspective, it's not apparent that producing male offspring is always a bad idea. Do couples with two sons have fewer descendants than those with two daughters? It can depend on the sex ratio in the population. If a human couple produces one offspring of whichever sex is in the minority, their offspring may have an easier time finding a mate.

But what about cross-fertilization? If a female cloned herself, her offspring would have all of her genes, rather than just half of them. So the frequency of genes for self-fertilization would tend to increase, unless individuals resulting from cross-fertilization were more likely to survive and reproduce. An offspring with half as many of one's genes, but a 2.1-fold better chance of survival (maybe because a sexual partner contributes different disease-resistance genes) gives a greater increase in fitness. So, one key to understanding the evolution of sex (cross-fertilization) is to measure the survival of individuals with one parent versus two, under conditions that plausibly occurred at critical points in a species ancestry.

This week's paper, "Mutation load and rapid adaptation favour outcrossing over self-fertilization", set out to "recapitulate the evolutionary process under the specific conditions predicted to favour either selfing or outcrossing." Levi Morran, Michelle Parmenter, and Patrick Phillips used the nematode, C. elegans, which consists of males and hermaphrodites. (This mix, and the lack of pure females, suggests there can be individual benefits to maleness, whatever the consequences for the population as a whole.) They used genetic manipulation to make populations that only self-fertilized or never self-fertilized, exposed them to high mutation rates or to a bacterial pathogen, and let them evolve.

]]> Their hypothesis was that cross-fertilization would limit the accumulation of bad mutations: if two individuals with two different bad mutations mate, some of their offspring will get both mutations and die, but some will get neither, whereas self-fertilizing populations may not have any mutation free individuals. Sure enough, mutations accumulated in the self-fertilizing population, resulting in decreased fitness. Cross-fertilization was also beneficial to the populations exposed to the pathogen: the population made to cross-fertilize evolved resistance, perhaps because they could combine good mutations from different parents.

As discussed above, however, just because some trait benefits the population as a whole doesn't guarantee that it will evolve. So a more interesting results used populations where the amount of cross-fertilization was allowed to evolve. An increase in mutation rate caused two different strains to evolve more cross-fertilization. Pathogen exposure seemed to have a similar effect, although there was a lot of variability.

Previously, it was thought that even the low rate of natural cross-fertilization in this species was enough to provide most of the benefits, but they saw improvements with additional cross-fertilization. This was achieved by increasing the percentage of males, which they suggested would provide additional benefits via sexual selection. If males fight over females and the healthiest males win, or if females choose the healthiest males, maybe we aren't so useless to our populations after all.

Evolving resistance to cheaters

2009-10-16T00:01:29Z

This week's paper, "Cheater-resistance is not futile" was published in Nature. It describes experimental evolution of the social amoeba Dictyostelium, whose propensity to cheat other members of its species was discussed by Will Ratcliff in a recent guest post titled "Sneaky slime molds."

When two Dictyostelium strains are mixed in a reproductive structure, cheaters contribute fewer cells to the stalk that holds up the reproductive spores. Could the presence of such cheaters select for cheater-resistance genes, just as the presence of owls or hawks selects for mouse genes that make their coats match the soil color?

]]> To find out, the researchers started with a genetically diverse population (the raw material for natural selection) and added a cheater. By definition, the cheater would tend to increase in frequency over cycles of reproduction, but they prevented that by using a cheater they could kill after it had had its effect on the relative reproduction of the other strains.

They did this several times, and each time one or two cheater-resistant genotypes took over the selected population. For example, starting with a population that made less than 40% of the spores when mixed 50:50 with the cheater, they evolved a population that made about 50%. (The cheater-resistant strain didn't push its advantage, apparently!)

In at least some cases, they identified the specific mutation that let their mutant hold its own against the cheater. The gene "has no annotated homologues in other organisms", so it's probably not a universal anticheater gene. In fact, it didn't even work against all Dictyostelium cheaters. Still, it would be interesting to know how it works at the molecular level.

Meanwhile, cooperators take heart. It's possible to keep cheaters under control, without becoming a cheater yourself.

Darwin at the Smithsonian

2009-10-12T18:29:06Z

I recently had two or three hours to spend at the Smithsonian, en route to the airport. I hadn't been to the natural history museum for awhile, and was interested to see how they were celebrating Darwin's anniversaries this year. Pretty well, it turns out. Banners outside advertised a Darwin exhibit and "Plants and butterflies: partners in evolution." Inside, there was apparently an organized "Evolution Trail", which I didn't have time to follow.

The Darwin exhibit is off the entrance hall with the elephant and has a mix of biographical and scientific exhibits. My main criticism was their definition of "co-evolution" as being limited to evolution for mutual benefit. Evolutionary arms races (e.g., between hosts and parasites) are also coevolution. The entrance hall on the other side, where I came in, has two display cases of Darwiniana.

The butterfly exhibit was dominated by a live butterfly room inside a larger room with displays on the coevolution of plants and butterflies, with fossils labeled "examine the evidence." I was happy to pay $6 admission to the butterfly room since I wanted to make a donation anyway and enjoyed having a frittilary land on my nose.

Near the Oceans exhibit was a display of Burgess Shale fossils I hadn't seen before, including Pikaia, a tiny 500-million-year-old chordate. We chordates have evolved a lot since then. Nearby were some fossil stomatolites.

The mammal room was great, focusing on adaptations in everything from bats to giraffes (splaying front legs to drink, with an explanation of adaptations to limit blood flow to head) to pangolins with termite mounds. Right in the middle of the floor was a window down to fossil hominid footprints.

I wish I could have stayed longer. One problem with a quick visit to the Smithsonian is that post9/11 hysteria has closed most of the bag-check rooms. You can't bring your luggage into the museum and if you leave it somewhere, they'll try to detonate it. (Luggage made of sapient pearwood can defend itself, but I wouldn't recommend bringing it to Washington!) But here's a secret tip for my regular readers only: the 4th St. entrance to the National Gallery still has a check room, complete with x-ray machine. Don't tell too many people, or they'll probably close it.

Coming up in March: the Hall of Human Ancestors!

Local TV new blows Ardipithecus story

2009-10-02T15:32:13Z

If you don't believe in evolution, you might not want to listen to this next story. Scientists reported this week on a new fossil, possibly a human ancestor, older than Lucy. The good news is, we're not descended from chimps after all. The bad news is, chimps and humans are descended from the same ancestor.

That's a paraphrase of how our local TV news covered Ardipithecus ramidus, the fossil hominid discussed in a series of papers in this week's issue of Science. Read all about it on Carl Zimmer's blog. The TV anchor didn't say which scientists claimed we are descended from chimps, perhaps because no scientist has made that claim. Chimps have evolved over the six million years or so since our last common ancestor, including their split with bonobos. Can we expect the story below on the TV soon?

Startling breakthrough in human genetics! You aren't descended from brother after all, or even from your cousin. You and your brother still have the same parents, and you and your cousin have the same grandparents, though. I hope that doesn't upset you too much.

We don't know for sure that present-day humans are descended from Ardipithecus . It's a reasonable hypothesis, but any hypothesis is, by definition, subject to possible disproof. For example, if we found another fossil that was clearly much more similar to modern humans, dating from the same time or earlier, then we'd conclude that Ardipithecus probably has no surviving descendants.

But this species probably isn't too far from the direct line of descent between our common ancestor with chimps and modern humans. Suppose you wanted to know what your great grandmother looked like, but there was no surviving picture of her. If you had pictures of her sister or her daughter, that would give you some idea, even if all her living descendants are descended from a son.

Of course, much of what we know about our ancestors now comes from analyzing DNA in humans and closely related species. We can figure out when vitamin C synthesis was lost or adult lactose tolerance gained, for example. But we don't yet understand development enough to predict height, foot shape, etc., from inferred DNA sequences of ancestral species. So keep those fossils coming!

Off topic: Frank view of blasphemy

2009-09-30T15:53:03Z

A couple of months ago, I read this New York Times article by economist Robert Frank, suggesting that Darwin's ideas may be a better guide to economics than (popularized versions of) Adam Smith's ideas. I was impressed and have been reading his books with considerable interest.

Many of his economic ideas parallel ideas I'm exploring in my book on Darwinian Agriculture. A singer, runner, or lawyer who's only 1% better may make ten times as much money, just as a leaf that's only 1 mm above the leaf of a competing plant may have ten times the photosynthesis. "Arms races" among humans -- working overtime will let you afford a house that is more expensive than average, so that your kids can go to a better-than-average school, but if everyone works overtime half the population still sends their kids to below-average schools -- parallel arms races among plants -- being taller than your neighbor means more photosynthesis and so more seed production, but if every plant grows taller that doesn't increase total photosynthesis and wastes resources on tall stems. And so on.

But today, in honor of Blasphemy Day, I want to summarize an interesting idea from his book, Choosing the Right Pond.

Freedom of speech is often presented as an "inalienable right", perhaps granted by (though never actively protected by) some hypothetical Creator. Frank suggests an alternative origin, based on freedom of association and economies of scale....

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Although migration in and out of most countries is somewhat restricted, a sufficiently motivated person can often evade those restrictions. Mobility within countries is typically even less restricted. So freedom of association is, to some extent, a truly inalienable right.

Often, people would prefer to associate with those who share their views on particular issues. But no two people agree on everything. The larger the group, the more areas of disagreement. You may be able to find a small country where most people share most of your views, but any large country is likely to include many people with different, perhaps deeply offensive, views.

Now, add economies of scale. There are many advantages to living in a larger country. Trade within countries isn't hampered by borders or tariffs. Bigger countries have more influence on international agreements. And so on. If you want the advantages of living in a larger country, you have to accept (in some sense) sharing it with those with different views.

Back to blasphemy. Hearing or seeing their religion (Islam, Christianity, Gaea/group-selection, whatever) or national/tribal symbols insulted often upsets people. Frank argues that blasphemy may sometimes actually harm people, in the same sense that noise or smog does, even if the only physical effect is an increase in stress hormones. This was a new idea for me, but I think he may have a point. But, he continues, preventing people from speaking their mind also causes stress.

You can imagine a market-based approach to this problem, where religious zealots and aspiring blasphemers discuss how much money to exchange, and in which direction, to compensate zealots for not having to hear blasphemy or to compensate nonbelievers for restricting their freedom. But the transaction costs would be huge, particularly in a large (and hence inevitably diverse) country, where one person's blasphemy is another's dogma.

A better solution is to classify hearing offensive speech as one of the costs of living in a large country. You may object to noise ordinances that limit your right to hold late-night parties or you may think you pay more than your share of taxes. Of course you can work to change those laws, but no large group is going to agree with you on everything. Get used to it.

Or move to some tiny country whose laws are more consistent with your views. But be prepared for disappointment. Northern Ireland, Bosnia, Iraq, and the Palestinian Territories apparently aren't small enough to ensure unanimity. I bet Quebec wouldn't be either.

Happy Blasphemy Day!

Off topic: Sears spied on customers

2009-09-25T21:07:29Z

Sears tricked customers into installing software that recorded:

"the contents of shopping carts, online bank statements, drug prescription records, video rental records, library borrowing histories, and the sender, recipient, subject, and size for web-based e-mails. The software would also track some computer activities that were not related to the Internet."

The Federal Trade Commission asked them to destroy the data and to be more honest about their plans next time they do something like this. I wonder whether that is a strong enough punishment to deter similar activities by other companies?

I hadn't seen anything about this in the news before reading about it on Bruce Schneier's blog. Why isn't he in charge of Homeland Security?

Guest Blog: Sneaky slime mold

2009-09-21T17:22:27Z

Slime molds allocate less to costly public goods when sharing then when alone.

(Special Guest Blogger: Will Ratcliff )

The slime mold Dictyostelium discoideum ('dicty' for short) spends most of its life alone, hunting soil bacteria and yeast. But when food runs out, tens of thousands of individuals aggregate into a mobile slug (cool youtube video) which crawls to an advantageous place and differentiates into a ball of spores on top of a long stalk. Individual dicty either become a dead stalk cell or a reproductively viable spore.

© Copyright, Mark Grimson and Larry Blanton

What possible incentive could there be for a dicty to sacrifice its life (become a stalk cell) for the benefit of those that become spores? If you answered 'there is no direct advantage to dying for others', you're right! Nonetheless, kin selection can lead to this type of self-sacrifice if a) the dicty in the stalk are highly related to the dicty that form spores (so are highly likely to have the same "unselfish genes"), and b) spores benefit from being higher off the ground (better chance of dispersal?).

But what happens when slugs are composed of more than one genotype? Here stalk formation becomes a 'tragedy of the commons' in which it is in each clone's interest to cheat, letting the other clone form a greater fraction of the stalk. So do dicty cheat? If so, how do they do it?

The short answer, as reported by Buttery et al. in the paper Quantification of Social Behavior in D. discoideum Reveals Complex Fixed and Facultative Strategies recently published in Current Biology is that:

Yes, dicty cheat; they cheat like crazy.

There are two ways in which a dicty clone in a mixed slug could cheat, producing less stalk and leaving more spores than its competitor....

]]> First, the dicty clone could have a higher intrinsic frequency of spore formation. In some clones, most cells become part of the stalk, putting their spores high up in the air, while others favor shorter stalks and thus produce more spores. When mixed together, a clone that forms many spores might automatically cheat a clone that forms a lot of stalk, benefiting from the tall stalk while contributing relatively little to its construction. Second, a dicty clone may sneakily increase its frequency of spore formation when in a mixed slug, relative to what it would do alone, letting the other strain make most of the stalk.

The authors tested 6 natural isolates that varied substantially in their intrinsic frequency of spore formation, and made all possible combinations of two-genotype mixed slugs. What they found is that 5 out of 6 genotypes cheated facultatively, forming more spores when in a mixed slug then when alone. Surprisingly, strains that formed more spores in mixed slugs were also able to keep the competitor strain from doing the same to them . This is a really cool result, demonstrating that evolutionary conflict over stalk production has led to this humble slime mold's ability to measure social context and preferentially cheat nonrelatives.

But here's the catch: while facultative cheating was rampant, it seemed to have little overall impact on fitness (here measured as spore number alone, ignoring the potentially important but unknown effects of stalk size) under test conditions. The fitness rank order of the 6 strains in mixed sporangia was almost completely determined by each strain's intrinsic spore:stalk allocation.

The evolutionary persistence of genes for facultative cheating suggests that it was sometimes important to these strains ancestors in the wild, but that remains to be shown. This is great work, but is hampered by the current black-box status of this microbe's ecology. Stalks are presumed to be beneficial, otherwise natural selection would have long ago eliminated them, but the quantitative benefit of greater stalk height is currently unknown. As a result, the authors had to define fitness only in terms of the number of spores formed. Their 6 strains that varied in spore:stalk ratio therefore differed greatly in 'fitness', but each might have the stalk:spore ratio that maximizes fitness in its source environment, if the benefits of greater stalk size are considered. If this were the case, mixed slugs in the wild would usually form between strains with similar stalk:spore ratios. Once differences in that ratio are taken out of consideration, the fitness consequences of facultative cheating may in fact be quite large.

How to maybe possibly get a grant

2009-09-18T17:41:09Z

I'm not doing a paper-of-the week (although I'm expecting a guest post) because I'm too busy reading a bunch of proposals for a grant panel. I can't give any details, of course, but here are some general observations that may be of interest to people who apply for or fund grants.

So far, every proposal I've read has seemed worth funding. This was not true the last time I served on a similar panel. Maybe the word has gotten out that grant funding is highly competitive, so few people bother sending weak proposals? This makes it easier to understand why some of my own recent proposals were rejected, often for what seemed like minor problems.

Unfortunately, we can only fund a small fraction of the proposals submitted. Of course, we could fund more proposals if we gave each group less money. There might be some merit in that approach, but I'll leave that topic for another time.

For those who are writing or thinking about proposals, here are some generic tips:

]]> You need a good idea (typically, an important question and a plausible way to answer it) or a few related good ideas and (at least in biology) some preliminary data showing your idea might work. If you don't already have a grant, it may be hard to get those preliminary data. Someone should do something about this problem, but you need to realize that you're competing with proposals that do have preliminary data.

Given the strength of the competition, research that "may be relevant to" something important (a question that lots of people want the answer to, or a solution to some important practical problem) is probably going to rate lower than research that will actually answer the important question or solve the important problem. If you can't reasonably promise that from your current proposal, can you at least show how it's an essential (rather than optional) step towards that goal?

To be competitive, you need to have published something related to the proposed work. If you've published one or two relevant papers each of the last 2-3 years, I'll be pretty confident that you'll publish your results from a new grant promptly. Unpublished results are much less likely to get used, even if you tell a few people about them at a meeting or something, so don't expect public funding if you don't publish. Maybe we shouldn't expect as many publications from people without past grant support; I'll have to get the grant program's guidance on that.

Make life easy for reviewers! Author-year citation (Adams, 1979) is better than numbers (42); if I already know the paper, it saves time; if I don't, and I look it up (maybe just the abstract), it's easier to remember. Avoid acronyms nonspecialists don't know. If there are one or two you need to use repeatedly, define and use. Otherwise, it's better to spell it out or use a plain-English substitute: "the sensor" [described when first referred to], rather than WTFIANAEE. Both of these suggestions cut into the space you could otherwise to repeat vague claims for how important your work is or provide details on how many microliters of master mix you plant to use. Do explain once why your work is important (preferably to people beyond your subspecialty) but data showing that a method works in your lab is more convincing than minuscule detail of what you plan to do. That's my opinion, anyway.

If your proposal isn't funded the first attempt -- this is now common, even for pretty good proposals -- assume that you may get some of the same reviewers again, but most will be new. So address pat reviewer concerns in a constructive way, without belaboring the point.

Applied Evolution Summit

2009-09-11T18:40:47Z

I've just agreed to give a talk in January at the Applied Evolution Summit: a small group of experts meeting at an island research station near the Great Barrier Reef to apply evolutionary biology to critical problems in human health, agriculture, fisheries, etc. It might surprise some evolution denialists to learn that pornography, abortion, atheism and "death panels" are not on the agenda, just science. Of course, when we talk about how global warming is affecting the coral reefs critical to some fish, we may need to go look!

I'm going to try really hard to finish my book before the meeting, which will keep me quite busy until then. I don't teach regular classes -- as an adjunct professor, I'm paid only from our grants -- but reading proposals for a grant panel, writing a paper on "spiteful solar tracking" in alfalfa for Evolutionary Applications, and helping my hard-working and brilliant grad students with methods and manuscripts can't wait until my book is done. So I may be posting only sporadically for a while.

Where do new genes come from?

2009-09-04T18:24:39Z

When a few members of a family have a gene not found in most other members, one explanation is that the gene is newly evolved, rather than inherited from the common ancestor of that family. (The other possibility is that their ancestor had it, but most descendants lost it.)

New genes often turn out to be copies of old genes, sometimes with modifications that give them very different functions. But a paper just published in Current Biology reports "Emergence of a new gene from an intergenic region", rather than duplication of an existing gene....

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One definition of a gene is "a section of DNA which, if altered, has some effect on phenotype (observable traits)." Many genes are transcribed into messenger RNA and then translated into protein (perhaps an enzyme). But there is an increasing list of examples of genes whose phenotypic effects depend on activity by the RNA transcript, which may never be translated into protein. Such genes often have a regulatory function, controlling the expression of other genes.

The gene reported in this paper was detected as an RNA transcript in house mice and some of their close relatives, but not in more distant relatives like rats. Their analysis of the family tree for the gene suggests that it evolved about 3 million years ago, after the last common ancestor of mice and rats lived.

The new gene is apparently not translated into protein. Antibodies designed to detect the protein, if it is made, didn't find any. Also, evolutionary changes in the DNA sequence appear to be indifferent as to protein structure: DNA-base changes that would have no effect on protein amino acid sequence were about as common as those that would effect the protein.

There was a phenotypic effect, however, meeting our criterion for a gene. When the researchers knocked out the DNA corresponding to the transcript, sperm motility decreased. Apparently the RNA transcript had some beneficial effect on expression of other genes.

Although the DNA was in every cell, the RNA transcript was produced almost exclusively in the testis. Apparently conditions for gene expression are looser there than elsewhere, so that a variety of mutations can get a stretch of DNA transcribed. Most such mutations are presumably harmful, but the mice with beneficial mutations (like the one described in this paper) have increasing representation in successive generations.

Effective communication on preserving crop diversity

2009-09-02T14:20:48Z

This talk by Cary Fowler, on the Global Seed Vault at Svalbard, is worth watching both for the content and as a model for effective public speaking. For that reason, I've categorized it under "careers in science" as well as "agriculture." Note the lack of bullet-point slides!

[Note added 9/11: text slides can make presentations boring, but handouts of text slides help students focus on understanding rather than scribbling notes. So I'm going to cut down on text slides in talks at meetings, but not necessarily in guest lectures to undergraduate classes.]

It's worth noting that even dry, frozen seeds may lose viability in storage. (You could probably still recover DNA, but that's only of practical value for the few traits, if any, whose value can be identified from DNA sequence alone.) So it's good to take seeds out of storage and grow fresh seed periodically. Usually, you want to do this in a way that minimizes natural selection in the seed-increase environment, to avoid losing traits that were useful where the crop was grown originally. For example, you want plants far apart enough that tall plants don't shade shorter neighbors enough to keep them from producing seed. And you don't want plants that were particularly prolific in the seed-increase environment to be over-represented in your next stored sample. Preserving crop diversity is a vastly under-funded activity, although that is true of most areas of agricultural research without immediate links to short-term profit.

Although even a few stored seeds can be multiplied enough in a few years to deal with slowly developing problems, such as climate change, if there's a global wheat epidemic you need at least enough disease-resistant seed on hand that one cycle of seed multiplication will meet farmer needs for the next growing season.

This is scary

2009-09-01T22:30:24Z

Amazon.uk and a couple of other sites are advertising my book before I've even sent a completed version to Princeton University Press. I'm fairly happy with what I've written so far, but I'm not sure I'll finish this month.

Amazon.com doesn't have my book listed yet, but they are selling a crop physiology book with a chapter I wrote on Darwinian Agriculture.

Peacock comment

2009-08-29T16:44:27Z

Most of the "comments" I get on older posts are commercial spam, which I delete. But if you're interested in a creationist comment on Dave Wisker's guest post on peacocks, here it is. It seemed to be original rather than cut-and-paste, so I approved it, but did add some comments of my own.

Are antibiotics a weapon or a signal?

2009-08-27T16:40:51Z

(Guest blog by my PhD student, Will Ratcliff)

If we get a nasty bacterial infection, we all know to go to the doctor for antibiotics. Few of us stop to think of where these antibiotics come from, which is too bad, because their origin is rooted in the stuff of a James Bond film: bloodsport and espionage. Scientists put a few different microbes on a Petri plate, let them duke it out, and then steal the chemical secrets of the victorious strain. Antibiotics are thus considered by most microbiologists to be pure weaponry, honed by natural selection for the most effective killing (or disabling) of competitors at the lowest cost.

But some recent papers suggest a new hypothesis: antibiotics are actually signaling molecules that happen to be toxic at high doses (Mlot 2009). As evidence for this view, researchers note that microbes exposed to antibiotics at sublethal concentrations don't simply shrug off the insult and go about their business: they react. Some bacteria turn on their SOS response, some make biofilms, some fail to make biofilms, some get less virulent (Shank and Kolter 2009), and yet others more virulent (Linares et al. 2006). These responses appear to vary among species without a general pattern.

So are antibiotics serving as a weapon or a signal?

Let's start at square one: what do they mean by signal? Many of the papers in this literature seem to use signal to mean "molecule produced by species A that elicits a response in species B other than death". But to evolutionary biologists, it matters why species A produces the signal and why species B reacts as it does....

]]> According to Steve Diggle et al. (2007), communication can be divided into three categories depending on the fitness consequences to each party :

The defining feature of a signal is that it has evolved because it increases the fitness of both the producer and the receiver. So we arrive at the central evolutionary problem with signaling: when is it beneficial to expend energy to provide another organism (perhaps of another species) with information that will increase its fitness?

A few scenarios I've thought up -- I'm sure there are more -- are A) when this reduces chances that you or your kin will be injured or eaten (e.g. I'm poisonous and if you eat me we'll both regret it) B) when this deters potential competitors from inhabiting the same area as you or your kin (e.g. I'm already halfway done with the food, and am not inclined to share, so you should probably go somewhere else), or C) when it is necessary for the initiation or maintenance of a mutualistic interaction, like the a legume root nodule by rhizobia. For cases A or B, at least, the sender may benefit from sending this message even if it is false, an example of coercion (or at least manipulation) analogous to Viceroy butterflies or back-arching cats that appear larger than they really are.

Before we can state with any confidence that an antibiotic is a signal, we need to know if producing and responding to a sublethal dose of the antibiotic produces benefits for both the producer and the receiver. Benefits like 'not dying from the antibiotic' don't count, nor does 'going into a biofilm preadapts a microbe to unexpected protozoal grazing '. These are questions that will probably be answered as microbial ecology moves forward.

If sublethal doses of antibiotics aren't signals, how do we explain their effect? Biofilm formation by bacteria exposed to antibiotics may increase their antibiotic tolerance, increasing their fitness at the expense of the antibiotic producer. From our previous definitions, the antibiotic would be a cue, not a signal. Similar arguments could be concocted for the production of detoxifying enzymes like β-lactamases or turning on the SOS response. An even simpler hypothesis is that some of the observed responses are not behavioral, but are the observable impact of an injury. Mucking about with a bacterium's ribosomes may not kill it, but it will likely leave some measurable impact.

Finally, antibiotics may simultaneously act as both a weapon and a signal. Assume that the concentration and effectiveness of an antibiotic drops off with distance from a producing microbe. Low concentrations of antibiotic may be an ineffective weapon, but can still effectively signal that any further encroachment on the antibiotic producer's turf is dangerous. Note that avoiding the killing zone of an antibiotic increases the exposed microbe's fitness (it does not die) and that of the producer (competition from other microbes is reduced). Right now this is pure speculation, but I wouldn't be surprised to find out that it's true.

Mixed up in all this is a general misunderstanding of the processes that natural selection optimizes. Linares et al. (2006) stated that:

"We thus could start to envisage a Copernican turn-about for the role of antibiotics in nature: from weapons involved in microbial struggle for life to collective regulators of the homeostasis of microbial communities."

This is essentially an old-school, group-selection argument, positing that individual species have evolved mechanisms to regulate the broader community because communities that are regulated do better. However, since the rate at which communities reproduce and die is slow relative to that of individual microbes, and their species composition is highly fluid, individual selection and kin selection swamp community-level selection. It is very unlikely that individuals would evolve mechanisms for the regulation of the community as a whole.

The bottom line: Simply observing that bacteria respond to sublethal antibiotic exposure does not provide any evidence that antibiotics evolved for the purpose of signaling or have been appropriated as a signaling agent. Indeed, even if antibiotics act only as a weapon, we expect bacteria exposed to sublethal antibiotic concentrations to respond either by being injured, or by acting to minimize injury (antibiotics acting as a cue). While we know that antibiotics can act as a weapon, we don't have any clear evidence that antibiotics act as a signal. Until we have these data, I wouldn't give the signaling hypothesis much weight.

LITERATURE CITED
Diggle S. P., A. Gardner, S. A. West, and A. S. Griffin. 2007. Evolutionary theory of bacterial quorum sensing: when is a signal not a signal? Philosophical Transactions of the Royal Society 362: 1241-1249
Linares J. F., I. Gustafsson, F. Baquero, and J. L. Martinez. 2006. Antibiotics as intermicrobial signaling agents instead of weapons. Proceedings of the National Academy of Sciences 103:19484-19489.
Mlot C. 2009. Antibiotics in nature: beyond biological warfare. Science 324:1637-1639.
Shank E. A., R. Kolter. 2009. New developments in microbial interspecies signaling. Current Opinion in Microbiology 12:205-214.