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Somatic DNA Modification in the Sp185/333 gene family of the California purple sea urchin: The Sp185/333 gene family has a central role in the echinoid innate immune system and its expression is significantly elevated in response to marine bacteria and pathogen associated molecular patterns (PAMPs). The family consists of an estimated 50(±10) members per genome that share a basic gene structure yet show significant sequence diversity primarily due to the mosaic appearance of short blocks of sequence called elements. The Sp185/333 genes are expressed in phagocytes, subpopulations of sea urchin cells called coelomocytes. Bioinformatic predictions suggest that Sp185/333 gene diversification may occur through frequent gene recombinations, conversions, deletions, and duplications. However it is not known whether these events may occur in the germline during meiosis and/or may occur in the soma during cell proliferation and differentiation. To address this question, we have used PCR and fragment analysis to characterize the Sp185/333 gene repertoire in sperm, tubefeet and coelomocytes from the same animal before and after immune challenge with heat-killed marine bacteria. The sensitivity of fragment length analysis has enabled us to identify gene sizes with great accuracy and to predict the gene copy ratios among different gene sizes. Surprisingly, results show that the Sp185/333 gene repertoire is significantly different in the post-challenged coelomocytes compared to the other tissues including pre-challenge coelomocytes, and consists of a different gene copy ratio as well as a new gene size. These results suggest the existence of a novel molecular mechanism for somatic DNA modification in the immune cells of the purple sea urchin in response to infection.