Microbial 'cheaters' help scientists ID 'social' genes

The first genome-wide search for genes governing social behavior has found that even the simplest social creatures — the amoebae Dictyostelium discoideum — have more than 100 genes that help regulate their cooperative behavior.

The study by scientists at Rice University and Baylor College of Medicine (BCM) was published online this week by the journal Nature. It marks one of the first large-scale attempts to combine evolutionary biology with genomics in a systematic search for genes tied to social behavior.

“This pool of genes is going to allow us to understand the genetic architecture of social behavior,” said co-author Joan Strassmann, Rice's Harry C. and Olga K. Wiess Professor of Ecology and Evolutionary Biology.

Though little understood, social cooperation among microbes causes major medical and industrial problems. Medically, cooperation underlies conditions as mundane as tooth decay to more serious conditions like chronic infections associated with medical implants. Industrially, slimy colonies of bacteria also foul filters at water treatment plants and other facilities, causing millions of dollars of damage each year.

Rice and BCM's genome-wide investigation took five years and required the detailed study of some 10,000 randomly mutated strains of D. discoideum. “The basic idea was to knock out genes at random and put each mutant through 10 rounds germination, growth and development to identify mutations that led to cheating,” Strassmann said.

Cheating mutations were found in more than 100 genes. Since there are advantages to be gained from cheating, Strassmann said the real mystery, from an evolutionary point of view, is how species like D. discoideum manage to keep cheaters from out-producing and eliminating cooperation altogether.

“This is just the beginning,” said co-author Adam Kuspa, BCM's S. J. Wakil Chair of Biochemistry and Molecular Biology. “Now we need to define key molecular mechanisms that might serve to stabilize cell cooperation.”

Strassmann said, “Cheating is to be expected. Cooperation is the real story. Since cheaters can thrive without these 100-plus genes, there has to be some other reason that they're still in the genome.”

D. discoideum are a common soil microbe. Their social order is one of the simplest in nature and it's an oft-used laboratory model for sociality. Though loners in times of plenty, D. discoideum form colonies when food is scarce, and work collectively to ensure their survival. About one fifth of the colony's individuals form a tall, thin stalk. The rest climb the stalk and clump together into a small bulb that can be carried away to better environs by the wind or on the legs of passing insects.

This simple social system poses an evolutionary conundrum for biologists; the individuals in the stalk give themselves up altruistically to support the colony, so what's to keep more selfish strains of D. discoideum from cheating the system, avoiding the stalk and out-reproducing their altruistic neighbors?

Strassmann and co-authors Gad Shaulsky, associate professor of molecular and human genetics at BCM, and David Queller, Rice's Harry C. and Olga K. Wiess Professor of Ecology and Evolutionary Biology, have identified a handful of cheater mutations for D. discoideum in prior studies. However, identifying cheaters was just the start in the genome-wide study. Cheaters were also subjected to additional tests so the team could find out how exactly how they cheated. The scientists also examined the cheaters' genetic code to locate the precise site of the cheater mutations.

The tests found that cheaters would exploit virtually any advantage to increase their share of spores in the next colony. While strategies for cheating varied at the proteomic level, the study found some cheaters use a common genetic strategy — they piggyback onto other essential functions. In a previous study, Strassmann and colleagues had identified a cheater that used the same strategy, and she said the broader study indicates that the “dual-function strategy” may be shared by other successful cheaters.

“The evolutionary opportunities for moves and countermoves appear to create a kind of genetic arms race in which cheating mutations are met with counter-mutations,” Strassmann said. “In this arena, cheating is often going to be piggybacked onto essential functions, making it hard to get rid of and hard to control.”