THE HYDRACTINIA ALLORECOGNITION COMPLEX ENCODES A LARGE FAMILY OF NOVEL IMMUNOGLOBULIN SUPERFAMILY MEMBERS

05 Jun 2019
9:20 - 9:40

THE HYDRACTINIA ALLORECOGNITION COMPLEX ENCODES A LARGE FAMILY OF NOVEL IMMUNOGLOBULIN SUPERFAMILY MEMBERS

Matt Nicrota, University of Pittsburgh

Aidan Huene1,2, Steven Sanders1,2, Ruoxu Chen3, Nicole Shigiltchoff4, Zhiwei Ma1,2, Anh-Dao Nguyen5, Sergey Koren5, James C. Mullikin6, Adam Phillippy5, Christine Schnitzler5,7,8, Andreas Baxevanis5, and Matthew L. Nicotra1,2,9

1Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA,
2Center for Evolutionary Biology and Medicine, University of Pittsburgh, Pittsburgh, PA
3School of Medicine, Tsinghua University, Beijing, China,
4UPMC Hillman Cancer Center Academy, Hillman Cancer Center, Pittsburgh, PA,
5Computational and Statistical Genomics Branch, Division of Intramural Research, National Human Genome Research, National Institutes of Health, Bethesda, MD,
6NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Rockville, MD,
7Whitney Laboratory for Marine Biosciences, University of Florida, St. Augustine, FL,
8Department of Biology, University of Florida, Gainesville, FL, 9Department of Immunology, University of Pittsburgh, Pittsburgh, PA

Colonial marine invertebrates are capable of allorecognition—the ability to discriminate between their own tissues and those of conspecifics. In Hydractinia symbiolongicarpus, a cnidarian model of allorecognition, compatible colonies fuse permanently, while incompatible colonies fuse temporarily or reject aggressively. These responses are controlled by a genomic region called the allorecognition complex (ARC). Previously, we and others identified two ARC-encoded allorecognition genes, Allorecognition 1 (Alr1) and Allorecognition 2 (Alr2). Both are singlepass transmembrane proteins with highly polymorphic extracellular regions. Allelic isoforms of Alr1 and Alr2 engage in homophilic binding only with isoforms of nearly identical sequence, suggesting a central role in self/non-self discrimination. Partial sequencing of the ARC revealed additional Alr-like sequences, but the full extent of this gene family was heretofore unknown. Here, we report a nearly complete 11.5 Mb reference sequence for the ARC. Annotation of this sequence reveals a family of 28 Alr genes and 15 Alr pseudogenes. Nearly half of Alr genes reside in one of three clusters, and mapping data is consistent with at least one previously unknown allodeterminant. Alr proteins possess extracellular regions consisting of tandem domains predicted to adopt immunoglobulin-like and fibronectin type III like folds. Like Alr1/2, several newly discovered Alr proteins are also capable of homophilic binding across opposing cell membranes. Comparative analysis across several ARC haplotypes reveals high levels of allelic polymorphism, gene duplication, and copy number variation, suggesting common mechanisms of genomic evolution with mammalian KIR and Ly49 systems.