Us and Them Among the Slime Molds

Scoop up some dirt, and you'll probably wind up with some slime mold. Many species go by the common name of slime mold, but the ones scientists know best belong to the genus Dictyostelium. They are amoebae, and for the most part they live the life of a rugged individualist. Each slime mold prowls through the soil, searching for bacteria which it engulfs and digests. After gorging itself sufficiently, it divides in two, and the new pair go their separate, bacteria-devouring ways. But if the Dictyostelium in a stamp-size plot of soil should eat their surroundings clean, they send each other alarm signals. They then use the signals to steer toward their neighbors, and as many as a million amoebae converge in a swirling mound. The mound itself begins to act as if it were a single organism. It stretches out into a bullet-shaped slug the size of a sand grain, slithers up toward the surface of the soil, probes specks of dirt, and turns around when it hits a dead end. Its movements are slow - it needs a day to travel an inch - but the deliberateness of the movements eerily evokes an it rather than a they.

After several hours, the Dictyostelium slug goes through another change. The back end catches up with the tip, and the slug turns into a blob. About 20 percent of the cells move to the top of the blob and produce a slender stalk. In order to keep the stalk from flopping over, these cells must produce rigid bundles of cellulose. Unfortunately, this cellulose also tears apart the amoebae that make it. The remaining amoebae in the blob then take advantage of the suicide of their slugmates. They slide up to the top and form a globe. Each amoeba in the globe covers itself in a cellulose coat and becomes a dormant spore. In this form the colony will wait until something - a drop of rainwater, a passing worm, the foot of a bird - picks up the spores and takes them to a bacteria-rich place where they can emerge from their shells and start their lives over.

The individual amoebae forming the stalk make the ultimate sacrifice so that other Dictyostelium may live and perhaps reproduce. These stalk-formers are not marked for death when they are born. When the amoebae mix together and the slug takes shape, the individuals that wind up in the front end of the slug will be the ones that form the stalk. In other words, they get a losing ticket in the Dictyostelium lottery. Aside from their rotten luck, they are indistinguishable from the amoebae that will survive as spores.

It is remarkable that stalk-forming amoebae should remain loyal to their fellow amoebae. Why should they willingly join a group of other amoebae when their loyalty will end in its and their death? Why shouldn't amoebae just stay away from the group and try to tough it out on their own? Of course, just joining a group is not a guarantee of loyalty. It's not hard to imagine amoebae finding a way to avoid the lottery of death. Actually, we don't even have to imagine them: scientists have discovered that some Dictyostelium will cheat their fellow amoebae, thanks to genes that ensure that they will form spores rather than stalks.

The puzzle of loyal amoebae is, at its foundation, a puzzle about evolution. In each generation, the members of a population will vary in all sorts of ways - in their size, in their shape, and in their behavior. Depending on the environment in which the population lives, some of these variations will give certain members an edge when it comes to surviving and reproducing. Genes that make successful variations possible will become more common, while the unsuccessful genes will become less common.

Imagine that a Dictyostelium divides in two, and one of its offspring undergoes a mutation that makes it cheat. It escapes the stalk lottery, and is guaranteed to become a spore. Over generations, its descendants would become more common because none of them have to die making a stalk. Its cheating gene would become more common in the population as a result. Other individuals might also mutate into cheaters on their own, and their offspring would thrive as well. Meanwhile, genes that promote cooperation would become less common. It might be possible for Dictyostelium to continue organizing slugs and stalks if only a small fraction of amoebae cheated. But in time natural selection could produce so many cheaters that a slug would fail to produce a stalk, dooming the spores to death. As plausible as this scenario may be, scientists don't see it happening in the real world. Dictyostelium is thriving happily in forests around the world. Clearly betrayal has not evolved to catastrophic levels. Why not?

A paper in the new issue of Nature sheds some light on the answer. It comes from the laboratory of David Queller and Joan Strassman at Rice University in Texas. They and their students went to the Houston Arboretum and dug up dirt from various spots. They extracted Dictyostelium purpureum from the dirt and raised the isolates in a lab. Then they mixed the slime mold together, adding several million cells from different pairs of isolates to a single dish. To tell the slime mold apart, they added green fluorescent dye to one isolate in each pair.

The scientists then waited for the slime molds to use up their food and then start to seek out one another. The results were striking. In any given stalk, almost all the cells came from one isolate or the other. One stalk glowed green, while the other remained dark. This result was in stark contrast to the results the scientists got when they mixed together fluorescent and non-fluorescent cells from a single isolate. In those cases, the stalks were half and half.

The scientists conclude that the slime mold has some way of telling apart cells of its own isolate from others. It has an "us versus them" view of the world.

Recognizing kin can be a powerful weapon against the evolution of cheating. In the 1960s evolutionary biologists William Hamilton and George Williams recognized individuals that share a lot of genes may evolve seemingly altruistic behavior towards one another. Even if one individual doesn't pass on its own genes, it may be able to help a relative pass on those genes more successfully. This dedidation to one's kin is not such a big sacrifice from an evolutionary point of view, because even if you don't get to reproduce, your sibling may. And some of your genes will be carried by your nephews and nieces. For these slime molds, becoming a stalk cell may not be such a terrible fate, evolutionarily speaking, because they help their kin survive as spores. It may pay more than cheating your way to the top. All these slime molds need is a way to tell which amoebae are kin and which are not. And the new study shows that they have a keen sense for us versus them.

What makes these results particularly interesting is that another species of slime mold, Dictyostelium discoideum, does not appear to stay with its kin so carefully. Queller and Strassman have found that unrelated D. discoideum will come together and form a single slug. Queller and Strassman suspect that amoebae join forces with strangers because they can form larger slugs. A larger slug can move farther and faster, possibly raising the odds that its spores will be able to reach fertile ground elsewhere.

But these mixed slugs offer more opportunities for cheaters, since kin selection is not so strong. One opportunity arises with the signals that tell each cell how to develop. Once amoebae become destined to develop into stalk cells, they still need to receive signals from neighboring cells to complete their development. You could well imagine that if a mutant amoeba became deaf to these signals it could avoid its fate as a dead stalk cell and become a spore instead.

Queller and Strassman have experimentally created these deaf amoebae by knocking out the gene D. discoideum needs to receive the development signal. (The gene is known as dimA.) The scientists mixed the dimA mutants with ordinary amoebae that were still able to receive the signal and turn into stalk cells. As they expected, the deaf amoebae did not become stalk cells. Instead, they prepared to become spores.

But when Queller and Strassman allowed these colonies to develop completely, they got a surprise. Most of the deaf amoebae failed to get into the ball of spores at the top of the stalk. The scientists don't yet know exactly why deaf amoebae can't become spores as well as ordinary ones. But what is clear is that dimA must have more than one role. In some cases, it acts as a signal that tells an amoeba to become a stalk cell. But in cells that are destined to become spores, it must also have some essential role in their development. It's common for genes to play different roles, and this research on slime molds suggests it may pose a major obstacle to the evolution of cheaters. The advantages a cheating amoeba gains by losing one of dimA's functions are wiped out by its losing another, equally important one.

It may also be difficult for D. discoideum to hide its cheating ways from its fellow slime mold. In another experiment, Queller and Strassman discovered that some mutant Dictyostelium cheat if they lose a gene called csA. Normally csA produces a sticky protein on the surface of amoebae. The csA mutants, by contrast, are slippery. When amoebae form a slug, these slippery mutants slide back to the rear, where they will have a good chance of becoming spores rather than stalk cells. The problem for a csA cheater is that this same sticky protein serves as a badge of loyalty. When individual Dictyostelium start moving toward one another in the soil, they recognize their neighbors by their csA badge. This sticky protein allows two Dictyostelium to glue themselves together and continue searching for other amoebae with the same badge. Cheating amoebae don't have the csA badge, and so they are shunned. Cheating can only benefit slime mold once they're in a group. If they can't get in a group at all, they're out of luck.

It looks like we'll have to wait for future research to show why one species of slime mold is so careful to stay with its kin, while another mingles with strangers. But these results make Dictyostelium a great model for scientists to study to understand the evolution of cooperation in bigger creatures, such as ourselves.

Source: NJ Mehdiabadi et al, "Kin preference in a social microbe," Nature, August 24, 2006, doi:10.1038/442881a