REANALYSIS OF THE EVOLUTION OF TUMOR NECROSIS FACTOR SUPERFAMILY IN VERTEBRATES
Ryan Heimroth, University of New Mexico
Ryan D. Heimroth1 and Irene Salinas1
1Center for Evolutionary and Theoretical Immunology (CETI), Department of Biology, University of New Mexico, Albuquerque, NM
Tumor necrosis factor superfamily ligand and receptor families (TNFSF) are an ancestral group of cytokines that play a vital role in many cellular functions such as cell differentiation and activation, and apoptosis. Additionally, TNFSFs are crucial for lymphoid tissue development and organization in mammals. Previous work has postulated that the progressive organization of lymphocytes observed in vertebrate evolution is a result of the diversification of TNFSF members. In order to revisit this hypothesis, we have reanalyzed the presence of TNFSF genes in newly available genomes from teleosts, coelacanth, amphibians, reptiles, birds and mammals. Additionally, seven lungfish transcriptomes were screened using both BLAST searches and HMM protein homology searches. Bayesian phylogenetic analysis was performed using the conserved TNF homology domain and the conserved TNFRSF motifs. Our results show expansions of TNF ligands in the South American lungfish (Lepidosiren paradoxa) with known functions in cell death and apoptosis in mammals but not of members involved in lymphoid tissue organization. African lungfish (Protopterus sp), in turn, express greater number of TNFSF genes with lymphocyte organization function. RT-qPCR analyses of 7 different P. dolloi tissues found a high constitutive expression of TNFRSF11A and IL7R in the nose, a region where lymphoid aggregation is known to occur in this species. We are currently performing comparative RNAseq analysis of laser-capture microdissected nasal lymphoid aggregates from P. dolloi as well as mammalian lymph nodes and Peyer’s patches. Our findings will unveil the molecular drivers of lymphocyte aggregation and confirm or reject the TNFSF evolutionary hypothesis.