Mechanistic analysis of a pathway that integrates allorecognition and altruism in Dictyostelium

Allorecognition is the ability to discriminate self from non-self or kin from non-kin. It is observed in various processes in every life kingdom, including immunity, development, sexual reproduction, and sociality. Cooperation is another ubiquitous property that involves interactions between individuals, ranging from interactions between single cells to interactions between groups of multicellular organisms. The evolution of cooperation is a challenging riddle and one of its most perplexing aspects is altruism – the act of benefiting another individual at an expense to the actor. Altruism is essential for cooperation but its evolutionary advantages cannot be understood without considering allorecognition. The greenbeard hypothesis bridges the concepts of allorecognition and altruism. Dawkins’ book ‘The Selfish Gene’ popularized Hamilton’s concept of a genetic locus that exhibits three key properties – displaying a discernable signal, recognizing that signal in others, and acting altruistically toward other individuals that display the signal. This idea was first considered as a hypothetical situation that was unlikely in nature, but studies over the past three decades have documented it in various organisms, including pathogenic bacteria, social insects, and even humans. Nevertheless, most of these studies did not fully account for the third criterion, namely a direct relationship between the greenbeard pathway and altruism. The allorecognition system of Dictyostelium discoideum relies on two polymorphic compatible membrane proteins, TgrB1 and TgrC1. It has been described as a greenbeard system in which TgrC1 confers the ability to signal kinship and TgrB1 confers the ability to recognize the signal, but the altruistic act of stalk formation has not been directly attributed to these proteins. We hypothesize that the tgrB1-tgrC1 pathway is a greenbeard system that confers the three elements of signaling, recognition, and altruism, and that mutations in the pathway genes confer falsebeard cheating behaviors. We have recently discovered that mutational activation of TgrB1 confers altruism in that cells that express the mutant protein enhance the sporulation efficiency of their wild-type counterpart at an expense to themselves. We also discovered that mutating downstream elements of the pathway confers falsebeard behaviors – inactivation of the rapgapB or rasD genes and activation of rapA cause cheating among cells that display matching TgrB1 and TgrC1 signals. These mutations are directly related to the tgrB1-tgrC1 system because knocking out rapgapB suppresses the developmental defects conferred by inactivation of the tgrB1-tgrC1 system, and rasD and rapA are tightly related to rapgapB signaling. These pioneering findings directly link allorecognition and altruism in one greenbeard pathway. We will study how activating mutations in tgrB1 confer altruistic behavior, and how mutations that modify rapgapB, rapA, and rasD cause falsebeard cheating. Using genetic, cellular, and transcriptome analysis approaches, we will rigorously test the greenbeard hypothesis and reveal the molecular and cellular details of the respective social behaviors.