Subfunctionalization of POMC paralogues in Senegalese sole (Solea senegalensis)

The precursor protein proopiomelanocortin (POMC) gives rise to a variety of biologically active peptides through cell-specific posttranslational processing. Two transcripts of pomc were found in the flatfish Solea senegalensis (ssePOMC-A and ssePOMC-B), that most likely represent subfunctionalized paralogues: ssePOMC-A lacks the N-terminal cleavage site for β-MSH, whereas ssePOMC-B cannot yield ACTH and completely lacks the opioid consensus sequence in the β-END region. An analysis of nucleotide substitution rates shows that the POMC-derived peptides possess well-conserved regions under purifying selection, except the β-END derived from POMC-B, which has undergone positive selection. The calculated Ks values for ssePOMC-A versus ssePOMC-B and zebrafish POMCα versus zebrafish POMCβ are 0.40 and 0.72, respectively, indicating that the zebrafish POMC paralogues started to evolve almost twice as early in evolution, and that the Solea POMC paralogues arose independently from the whole genome duplication event that gave rise to the zebrafish paralogues. This makes ssePOMC-B the first identified POMCα orthologue that lacks the opioid consensus. Furthermore, pomc-a expression is down-regulated in chronic stressed S. senegalensis juveniles, whereas pomc-b expression levels remain unaffected, indicating different physiological roles for both POMC paralogues. The distribution of functional POMC-derived peptide hormones over two pomc genes in S. senegalensis suggests subfunctionalization of the paralogues, a relevant notion when studying POMC function in endocrine responses.This work was partially funded by grants AGL2007-61211/ACU (Ministerio Educación y Ciencia of Spain) and Proyecto de Excelencia PO7-RNM-02843 (Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía) to J.M.M. The authors are grateful to “Planta de Cultivos Marinos” (CASEM, Puerto Real, Spain) for the donation of S. senegalensis. Y.W. is funded by Ministerio de Educación y Ciencia (Spain) through the program “Formación de Profesorado Universitario” (Ref: AP2006-03932). E.V. is funded by the SmartMix Program of the Netherlands Ministry of Economic Affairs and the Ministry of Education, Culture and Science.Peer reviewe