Sequence variations in 185/333 messages from the purple sea urchin suggest posttranscriptional modifications to increase immune diversity

The 185/333 gene family is highly expressed in two subsets of immune cells in the purple sea urchin in response to immune challenges. The genes encode a surprisingly diverse set of transcripts, which is a function of the variable presence or absence of blocks of shared sequences, known as elements that generate element patterns. Diversity is also the result of a significant level of point mutations. Together, variable element patterns and single nucleotide polymorphisms result in many unique transcripts. The 185/333 genes only have two exons, with the variable element patterns encoded entirely within the second exon. The diversity of the gene family may be the result of frequent recombination among the 185/333 genes that generates a mosaic distribution of element sequences among the genes. A comparative analysis of the sequences for the genes and messages from individual sea urchins indicates that these two sequence sets have largely different nucleotide sequences and appear to use different element patterns. Furthermore, the nucleotide substitution patterns between genes and messages reveal a strong bias toward transitions, particularly cytidine to uridine conversions. These data are consistent with cytidine deaminase activity and may represent a novel form of immunological diversification in an invertebrate immune response system. The Journal of Immunology, 2008, 181: 8585–8594. M olecular diversity among immune response proteinshas been observed in nearly all organisms, includingvertebrates, invertebrates, and plants (reviewed in Refs. 1, 2). In addition to the well-understood mechanisms in ver-tebrate somatic gene rearrangement of the Ig gene family (3)