Comprehensive Sequence Analysis of Parvalbumins in Fish and Their Comparison with Parvalbumins in Tetrapod Species

SIMPLE SUMMARY: If people are allergic to fish meat, this usually is because of an immune reaction against parvalbumin proteins in fish muscle. Fish have multiple parvalbumins with quite similar sequences, making a comparison between fish species complex. The present study is the first to do so in a thorough manner so that researchers interested in fish allergies can more readily understand the underlying molecular biology. In addition, we look at ancient sequence motifs that distinguish the major types of parvalbumins—such as oncomodulins and α-parvalbumins—that are found in both fish and tetrapod species. This should help researchers interested in parvalbumin functions to better understand the essence of each type of parvalbumin. ABSTRACT: Parvalbumins are small molecules with important functions in Ca(2+) signaling, but their sequence comparisons to date, especially in fish, have been relatively poor. We here, characterize sequence motifs that distinguish parvalbumin subfamilies across vertebrate species, as well as those that distinguish individual parvalbumins (orthologues) in fish, and map them to known parvalbumin structures. As already observed by others, all classes of jawed vertebrates possess parvalbumins of both the α-parvalbumin and oncomodulin subfamilies. However, we could not find convincing phylogenetic support for the common habit of classifying all non-α-parvalbumins together as “β-parvalbumins.” In teleost (modern bony) fish, we here distinguish parvalbumins 1-to-10, of which the gene copy number can differ between species. The genes for α-parvalbumins (pvalb6 and pvalb7) and oncomodulins (pvalb8 and pvalb9) are well conserved between teleost species, but considerable variation is observed in their copy numbers of the non-α/non-oncomodulin genes pvalb1-to-5 and pvalb10. Teleost parvalbumins 1-to-4 are hardly distinguishable from each other and are highly expressed in muscle, and described allergens belong to this subfamily. However, in some fish species α-parvalbumin expression is also high in muscle. Pvalb5 and pvalb10 molecules form distinct lineages, the latter even predating the origin of teleosts, but have been lost in some teleost species. The present study aspires to be a frame of reference for future studies trying to compare different parvalbumins.