Evolution of helical cytokines: a structural approach

Cytokines are small soluble factors retrieved in mammals and involved in several processes such as immunity and development. They are typically characterized by pleiotropicity, functional and receptor redundancy. In consideration of functional parallels between mammalian and invertebrate immunity, a lot of experiments have been dedicated to the unravelling of cytokine network in both protostomian and deuterostomian invertebrates. The presence of cytokine-like molecules has been evidenced by several morphological and functional investigations in different taxa of invertebrates, leading to the hypothesis that cytokines are molecules of ancient origin, present in metazoans before the division of protostomian and deuterostomian phyletic lines. However, all the recent molecular biology advances indicate that no sequence similarity can be retrieved between the known vertebrate cytokines and the whole genome of invertebrate species. On these basis, functional convergence has been proposed between 25 vertebrate and invertebrate cytokines. The functional convergence would be due to the lectin-like activity of vertebrate cytokines that can be retrieved also in some invertebrate molecules. In order to unravel this unsolved matter, we have adopted a new bioinformatics approach able to isolate proteins whose structure is comparable to that of mammalian helical cytokines from EST and protein databases. Through this method we have isolated a molecule from Drosophila melanogaster databases that presents the structural characteristics of a helical cytokine (Drosophila helical factor, DHF). Functional experiments performed on third instars larvae and SL2 embryonic hemocyte cell line of D. melanogaster demonstrated that DHF expression was increased after different immune challenges. From the present findings, it emerges that the contradiction between the amount of morphological and functional evidences and the absence of any homology between mammalian and invertebrate cytokines, could be explained by evolution of cytokine genes thereby conserving specific protein structures rather than amino acid or nucleotide sequences. From the present findings, it emerges that the contradiction between the amount of morphological and functional evidences and the absence of any homology between mammalian and invertebrate cytokines, could be explained by evolution of cytokine genes thereby conserving specific protein structures rather than amino acid or nucleotide sequences.