Growing evidence suggests that the purple sea urchin immune system is more complex than previously believed. Analysis of the sea urchin genome reveals a number of gene families with homology to vertebrate innate immune receptors, in addition to lectin and complement homologues. An additional immune-related gene family, 185/333, which lacks known homologues in other species, is characterized by extraordinary diversity and is strongly upregulated in response to immunological challenge. In addition to point mutations, alignment of the sequences requires the insertion of large gaps that define elements, the presence or absence of which defines element patterns. The genes are small (<2kb) with only two exons, the second of which encodes the majority of the element pattern. The genes contain a variety of types of repeats that allow for multiple alignments. The repeats within the genes, in addition to di- and trinucleotide repeats flanking the genes and their close linkage are thought to facilitate frequent recombination among members of the gene family, thereby increasing diversity. Although a large number of genes with unique sequences have been isolated, each individual element within the genes is composed of a limited number of similar, but distinct sequences. The mosaic distribution of these sequences among the 185/333 genes also suggests frequent recombination within this gene family. Analysis of 185/333 genes isolated from coelomocyte and sperm genomic DNA indicates that the diversification is not limited to coelomocytes. Comparisons between the 185/333 gene vs. message sequences isolated from individual animals reveals that very few element patterns or nucleotide sequences are identified from both genes and messages. The messages exhibit a strong cytidine to uridine substitution pattern when compared to the genes, suggesting a post-transcriptional RNA editing mechanism that mimics cytidine deaminase activity. Thus, the diversity of the 185/333 sequences is the result of frequent recombination among the genes that is promoted by various repeats and the structure of the gene cluster, plus putative post-transcriptional editing of the messages. The 185/333 system represents a novel mechanism for generating immune diversity in an invertebrate, and further supports the concept that all organisms require immunological diversity to survive.
|Advisor:||Smith, L. Courtney|
|Commitee:||Allard, Marc, Brown, Kenneth, Church, Sheri, Florea, Liliana, Johnson, Diana E.|
|School:||The George Washington University|
|School Location:||United States -- District of Columbia|
|Source:||DAI-B 69/02, Dissertation Abstracts International|
|Keywords:||185/333, Diversity, Gene family evolution, Immune-related gene, Innate immunity, Invertebrate, Strongylocentrotus purpuratus|
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