Insights into the early evolution of NF-kappaB signaling based on computational analyses of cnidarian genomes and transcriptomes
Files
Main dissertation
ForSite program written in python
ForSite outputs used in this study from Nematostella (NvT1 and NvC25 assemblies), Hydra, and Acropora. txt files are tab delimited
Date
2015
DOI
Authors
Lubinski, Tristan James
Version
OA Version
Citation
Abstract
NF-kappaB is an ancient transcription factor that is known to play a central role in regulating cellular stress responses in vertebrates and insects, including the innate immune response, and the response to a range of physiochemical insults such as UV radiation and oxidative stress. The early evolution of this pathway is not well understood, because little is known about NF-kappaB signaling in so-called basal animal lineages (e.g., sponges, cnidarians) or closely related outgroups to the Metazoa. Key to understanding the function of a transcription factor is to identify the target genes whose transcription it regulates. To investigate the regulatory role of NF-kappaB in basal animals, specifically the sea anemone Nematostella vectensis, I developed ForSite, a computational tool that identifies putative transcription factor binding sites in the genome in proximity to expressed genes, and I helped to generate a new annotated reference transcriptome for N. vectensis. After demonstrating that ForSite could be used to identify a set of genes enriched for known NF-kappaB targets in human, I applied ForSite along with multiple winnowing criteria (co-localization of p300 binding; evolutionary conservation of target genes) to identify a high-priority list of potential NF-kappaB targets in the anemone. Among the most convincing set of likely target genes are members of a conserved anti-viral pathway, which suggests NF-kappaB plays an ancient role in innate immunity that dates to the cnidarian-bilaterian ancestor. Application of ForSite to two additional cnidarian species, Hydra magnipapillata and Acropora digitifera, failed to show significant conservation of regulation of biological processes by NF-kappaB among the cnidarian species.