Fish are most primitive groups of jawed vertebrates, their complement Sorafenib Raf inhibitor system had evolved all three C3-activation pathways and the cytolytic pathway, showing many of the effecter activities recognized in the mammalian complements, such as target cell killing, opsonization, and anaphylatoxic leukocyte stimulation. Although fish complement system has showed a high degree of structural and functional conservation of the complement pathways and their components comparing with mammals, striking features of the fish complement system were also unveiled, including prominent levels of extrahepatic expression and isotypic diversity of the complement components. Whole-genome duplication is to be one of the major evolutionary events that shaped the genome organization of vertebrates. Three WGD events have been proposed in ancient vertebrate history: two at the origin of the group and a third specific to fish. The distinctiveness of fish complement system probably was the long evolution results of the ancient fish-specific genome duplication under the aquatic environment. Studies of the genomes of zebrafish and two close relative Tetraodontiformes have confirmed that ray-finned fish underwent a FSGD some 320–400 million years ago which might explain their evolutionary success. The third period of positive selection of C3 happened on ancestral mammalian lineage. After its discovery, intensive and detailed researches have focused on human complement system, more than 30 plasma and cell-surface complement proteins have been found. The complement system is known to be a highly sophisticated host-defense system that is engaged in both the innate and adaptive immunities. It involves in a range of functions from direct cell lysis to the enhancement of B and T cell responses. Given the multiple pathways of activation and the versatile functions of derived products of complement members, regulation of the complement system is complex and necessary. Activation of complement is critical for protection against pathogen infection; however, inappropriate activation of complement contributes to the pathogenesis of immunological and inflammatory diseases. To limit host destruction, the system makes use of both serum and cell surface regulatory proteins. In conclusion, although C3 gene is conserved from invertebrate to vertebrate, it had happened three periods of positive selection events during animal evolutionary history. Two happened on the ancestral lineages to all vertebrates and mammals, respectively, one happened on early period of fish evolutionary history. For the reason of huge differences between aquatic and terrestrial environments, the C3 genes of fish and mammals had experienced different evolution patterns. Major depressive disorder is a psychiatric disorder characterized by persisting depressed mood. The lifetime prevalence in western civilization is estimated to be approximately 10–15% and the World Health Organization has predicted that by the year 2020, MDD will be the second leading cause of disability worldwide.