Biological systems are notable for the existence of several distinct systems of molecular recognition. A small subset of recognition systems is sufficiently precise and sufficiently variable as to permit recognition of variation between individuals of the same species. Examples include in the realm of agriculture, the pollen compatibility system of plants, and in the realm of medicine, the immune receptors that recognize disease and disease receptors that evade immune receptors. An additional prominent class of highly variable, yet precise determinants are those that control whether colonial animals fuse or reject on contact. The genes that control such phenomena have recently been identified. This project will determine the extent of variation in these genes in natural populations, whether this variation is primarily in the sequence of corresponding genes or whether that variation is structural, and determine whether the variation documented is or is not sufficient to explain fusion and rejection in the wild. The broader impacts of this work include the possibility, based on comparable studies of highly variable recognition systems, of identifying of novel mechanisms by which genetic variation is created and/or maintained. In addition, the project will provide a unique interdisciplinary training in molecular genetics and marine biology for jointly trained graduate students, as well as to continue to train underrepresented minorities and participate in local high school research curricula.
Allorecognition reactions, wherein an individual detects and reacts to a conspecific on the basis of cell-cell contact, are widespread amongst colonial marine animals. Studied for over a century, these reactions hold special interest as they are natural analogs to graft rejection and the immunological challenges accompanying pregnancy. The key questions defining the field are: (1) What molecules are responsible for the recognition event? (2) How is the extraordinary specificity of recognition generated and maintained? (3) What cell biological processes mediate the rejection response? In the last funding cycle, our research program has succeeded in providing answers to all three questions. Specifically, we have identified two genes, alr1 and alr2 in the hydroid Hydractinia that encode allodeterminants, have shown that variation in these genes rival that seen in comparable molecules of the vertebrate immune system, and such variation is fueled by sequence donation from similar genes and pseudogenes, and shown that these molecules elicit a cascade of effects that include autophagy and necrosis, two prominent modes of cell death. The broader education outcomes of this report include the training in research of several graduate students (3), post-doctoral scholars (1) and undergraduates in research (10), several of whom are members of recognized minorities. Moreover, the project involved high-school students in research (3) and participated in museum related educational activities.
