The two key factors for the generation of the diverse antigen receptor repertoire in the human adaptive immune system are the products of the recombination activating genes 1 and 2 (RAG1 and RAG2). The identification of their homologs, spRAG1L and spRAG2L respectively, in the genome of the purple sea urchin, Strongylocentrotus purpuratus was unexpected as there is no evidence thus far of an adaptive immune system in invertebrates (including echinoderms), i.e. they lack at least one of its hallmarks, a diversified antigen receptor repertoire. During this fiscal year we got access to un-published genome sequence information from additional echinoderm species. Our hope is to be able to identify the RAG1 and RAG2 homologs in these genomes as well. Preliminary data suggests that at least one additional echinoderm, Lytechineus variegatus, also carries the RAG1/RAG2 gene pair in its genome. In addition, we performed RNA-seq experiments to determine the transcriptome of individual subpopulations of coelomocytes to gain additional information on their respective function based on gene expression patterns. An initial coarse analysis clearly shows differences in gene expression patterns. Our studies have major implications for the current model of how adaptive immunity evolved in jawed vertebrates, and will help to illuminate conserved features of how V(D)J recombination is tightly controlled to avoid potentially dangerous modifications of the genome.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000388-07
Application #
8736554
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$41,873
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Fugmann, Sebastian D (2011) RAG-2 unleashed: lymphocytes beware. Immunity 34:137-9
Litman, Gary W; Rast, Jonathan P; Fugmann, Sebastian D (2010) The origins of vertebrate adaptive immunity. Nat Rev Immunol 10:543-53
Fugmann, Sebastian D (2010) The origins of the Rag genes--from transposition to V(D)J recombination. Semin Immunol 22:10-6