Genomic view of the evolution of the complement system

Abstract

The recent accumulation of genomic information of many representative animals has made it possible to trace the evolution of the complement system based on the presence or absence of each complement gene in the analyzed genomes. Genome information from a few mammals, chicken, clawed frog, a few bony fish, sea squirt, fruit fly, nematoda and sea anemone indicate that bony fish and higher vertebrates share practically the same set of complement genes. This suggests that most of the gene duplications that played an essential role in establishing the mammalian complement system had occurred by the time of the teleost/mammalian divergence around 500 million years ago (MYA). Members of most complement gene families are also present in ascidians, although they do not show a one-to-one correspondence to their counterparts in higher vertebrates, indicating that the gene duplications of each gene family occurred independently in vertebrates and ascidians. The C3 and factor B genes, but probably not the other complement genes, are present in the genome of the cnidaria and some protostomes, indicating that the origin of the central part of the complement system was established more than 1,000 MYA.

Complement in age-related macular degeneration: a focus on function

“…The results of this search suggest that the oldest parts of the system are complement component 3 (C3) and complement factor B (CFB), which were identified in sea anemones of the phylum Cnidaria. 10 Cnidaria diverged from Bilateralia (which include vertebrates and therefore humans) B1300 million years ago, indicating that the basic complement system is at least of this age. 10 Given the central role of C3 and CFB in the complement pathways, it is not surprising that they are the oldest elements of the system.…”

“…10 Cnidaria diverged from Bilateralia (which include vertebrates and therefore humans) B1300 million years ago, indicating that the basic complement system is at least of this age. 10 Given the central role of C3 and CFB in the complement pathways, it is not surprising that they are the oldest elements of the system. The alternative pathway is the oldest of the complement activation pathways.…”

“…2,10 Tight coevolution of hosts (including humans) and infectious microbes has occurred throughout evolutionary history and resulted in the evolution of microbes that evade host immune recognition. Likely all successful infectious microbes have developed mechanisms to subvert or evade host complement attack by binding or mimicking complement proteins.…”

“…The lectin pathway evolved subsequently and was followed by the classical pathway. 10 Many of the complement genes contain small exons, which encode short peptides called short consensus repeats (SCRs) or complement control proteins, many of which have a specific enzymatic or binding function. 13 These exons have allowed rapid evolution of complement proteins by exon shuffling.…”

Too Much of a Good Thing at the Site of Tissue Injury: The Instructive Example of the Complement System Predisposing to Thrombotic Microangiopathy

“…3,4 In organisms such as Cnidaria (eg, anemones and coral) and protostomes (eg, crabs and nematodes), only a few complement components are present, but these are sufficient to constitute a primitive AP that provides an independent immune network. 5 The human complement system differs mainly by having a more sophisticated and directed recognition system featuring antibodies (the classical pathway or CP) and lectins (the lectin pathway or LP).…”