Pleiotropy as a mechanism to stabilize cooperation.

Most genes affect many traits. This phenomenon, known as pleiotropy, is a major constraint on evolution because adaptive change in one trait may be prevented because it would compromise other traits affected by the same genes. Here we show that pleiotropy can have an unexpected effect and benefit one of the most enigmatic of adaptations--cooperation. A spectacular act of cooperation occurs in the social amoeba Dictyostelium discoideum, in which some cells die to form a stalk that holds the other cells aloft as reproductive spores. We have identified a gene, dimA, in D. discoideum that has two contrasting effects. It is required to receive the signalling molecule DIF-1 that causes differentiation into prestalk cells. Ignoring DIF-1 and not becoming prestalk should allow cells to cheat by avoiding the stalk. However, we find that in aggregations containing the wild-type cells, lack of the dimA gene results in exclusion from spores. This pleiotropic linkage of stalk and spore formation limits the potential for cheating in D. discoideum because defecting on prestalk cell production results in an even greater reduction in spores. We propose that the evolution of pleiotropic links between cheating and personal costs can stabilize cooperative adaptations.

Cell polarity and locomotion, as well as endocytosis, depend on NSF.

NEM-sensitive factor (NSF) is an essential protein required during membrane transport. We replaced part of the endogenous D. discoideum NSF gene (nsfA) by a PCR-mutagenised library and isolated 11 mutants temperature-sensitive (ts) for growth. Two of these have been studied in detail. As expected, both are ts for FITC-dextran uptake by macropinocytosis, for internalising their surface membrane (monitored with FM1-43) and for phagocytosis. However, after 10-20 minutes at 28 degrees C, they round up and cease to chemotax, move or cap ConA receptors. They fully recover when returned to 22 degrees C. These cells carry out a normal 'cringe' reaction in response to cAMP, indicating that the actin cytoskeleton and this signal transduction pathway are still functional at 28 degrees C. The behaviour of these mutants shows that NSF-catalysed processes are required not only for the different endocytic cycles but also for the maintenance of cell polarity. As cell locomotion depends on a cell having a polarity, the mutants stop moving at high temperature. A tentative model is proposed to explain the surprising link between membrane recycling and cell polarity revealed here.