Evolution of the complement system C3 gene in Antarctic teleosts. Issue 2 (August 2015)

• Record Type: Journal Article
• Authors: Melillo, Daniela; Varriale, Sonia; Giacomelli, Stefano; Natale, Lenina; Bargelloni, Luca; Oreste, Umberto; Pinto, Maria Rosaria; Coscia, Maria Rosaria
• Is Part Of: Molecular immunology. Volume 66:Issue 2(2015:Aug.)
• Page Start: 299
• Page End: 309
• Publication Date: 2015-08
• Subjects: α′NT α′ N-terminal tag -- ANATO anaphylatoxin domain -- C3 third complement system component -- C345C C3, C4, C5 domain -- CS complement system -- CUB complement C1r/C1s, Uegf, Bmp1 -- LINCS linear constraint solver -- LNK linker region -- MD molecular dynamics -- MG α2 macroglobulin domain -- RACE rapid amplification of cDNA ends -- RMSD root mean square deviation -- RMSF root mean square fluctuation -- SAR short anchor region -- TED thioester containing domain; Antarctic teleost -- Complement system component C3 -- Anaphylatoxin -- Positive evolution -- Cold adaptation -- Molecular flexibility; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2015.03.247
• Languages: English
• ISSNs: 0161-5890

Abstract

Graphical abstract: Highlights: Antarctic teleost C3 genes underwent Darwinian selection. Positive selection modified sites crucial for the flexibility of the C3 molecule. Domain movements were found more pronounced in Antarctic molecules. Abstract: Notothenioidei are typical Antarctic teleosts evolved to adapt to the very low temperatures of the Antarctic seas. Aim of the present paper is to investigate sequence and structure of C3, the third component of the complement system of the notothenioid Trematomus bernacchii and Chionodraco hamatus . We determined the complete nucleotide sequence of two C3 isoforms of T. bernacchii and a single C3 isoform of C. hamatus . These sequences were aligned against other homologous teleost sequences to check for the presence of diversifying selection. Evidence for positive selection was observed in the evolutionary lineage of Antarctic teleost C3 sequences, especially in that of C. hamatus, the most recently diverged species. Adaptive selection affected numerous amino acid positions including three residues located in the anaphylatoxin domain. In an attempt to evaluate the link between sequence variants and specific structural features, we constructed molecular models of Antarctic teleost C3s, of their proteolytic fragments C3b and C3a, and of the corresponding molecules of the phylogenetically related temperate species Epinephelus coioides, using human crystallographic structures as templates. Subsequently, we compared dynamic features of these models by molecular dynamics simulations and found that the Antarctic C3s models show higher flexibility, which likely allows for more pronounced movements of both the TED domain in C3b and the carboxyl-terminal region of C3a. As such dynamic features are associated to positively selected sites, it appears that Antarctic teleost C3 molecules positively evolved toward an increased flexibility, to cope with low kinetic energy levels of the Antarctic marine environment.