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.

Fig. 1

Phylogenetic relationship among animals. Phylogenetic relationship among multicellular animals elucidated by molecular clock methods based on protein sequence data is shown. Only animal groups relevant to this review are included. The divergence times for the Arthropod/Nematoda or Mollusca/Annelida were not analyzed by this method and are arbitrarily shown in this figure

Fig. 2

Presence or absence of complement component genes in various animal groups. All complement components and related genes of human, as a representative of Mammalia, are shown, and the presence of the orthologous genes reported from the other animal groups are indicated by the reference numbers. Plus and minus indicate the presence and absence, respectively, of the orthologous genes in the assembled genome sequences of at least one representative species of each group. Genes located outside of the complement gene clusters in the phylogenetic tree, showing an uncertain orthologous relationship with complement genes, are indicated in red. Literatures cited here are: 1 Mavroidis et al. ; 2 Fritzinger et al. ; 3 Kaufman et al. ; 4 Kjalke et al. ; 5 Laursen et al. ; 6 Lynch et al. ; 7 Oshiumi et al. ; 8 Mahon et al. ; 9 Grossberger et al. ; 10 Mo et al. ; 11 Kato et al. ; 12 Kato et al. ; 13 Endo et al. and Kakinuma et al. ; 14 Endo et al. ; 15 Kunnath-Muglia et al. ; 16 Boshra et al. ; 17 Abelseth et al. ; 18 Samonte et al. ; 19 Zarkadis et al. ; 20 Nakao et al. ; 21 Kuroda et al. ; 22 Sato et al. ; 23 Sunyer et al. ; 24 Sunyer et al. ; 25 Sunyer et al. ; 26 Lambris et al. ; 27 Boshra et al. ; 28 Wang and Secombes ; 29 Sambrook et al. ; 30 Kato et al. ; 31 Franchini et al. ; 32 Nakao et al. ; 33 Sunyer et al. ; 34 Nakao et al. ; 35 Gongora et al. ; 36 Seeger et al. ; 37 Kuroda et al. ; 38 Yano and Nakao ; 39 Vitved et al. ; 40 Nakao et al. ; 41 Chondrou et al. ; 42 Zarkadis et al. ; 43 Papanastasiou and Zarkadis ; 44 Uemura et al. ; 45 Katagiri et al. ; 46 Kazantzi et al. ; 47 Yeo et al. ; 48 Tomlinson et al. ; 49 Nakao et al. ; 50 Kemper et al. ; 51 Boshra et al. ; 52 Boshra et al. ; 53 Fujiki et al. ; 54 Dodds et al. ; 55 Terado et al. ; 56 Smith ; 57 Terado et al. ; 58 Ishiguro et al. ; 59 Nonaka et al. and Nonaka and Takahashi ; 60 Nonaka et al. ; 61 Matsushita et al. ; 62 Takahashi et al. ; 63 Song et al. ; 64 Kimura et al. ; 65 dos Remedios et al. ; 66 Suzuki et al. ; 67 Endo et al. ; 68 Raftos et al. ; 69 Marino et al. ; 70 Nonaka et al. ; 71 Yoshizaki et al. ; 72 Azumi et al. ; 73 Dehal et al. ; 74 Kenjo et al. ; 75 Sekine et al. ; 76 Ji et al. ; 77 Miyazawa and Nonaka ; 78 Miyazawa et al. ; 79 Al-Sharif et al. ; 80 Smith et al. ; 81 Zhu et al. ; 82 Adams et al. ; 83 The C. elegans Sequencing Consortium ; 84 Dishaw et al. ; *1 H. Nagumo et al., unpublished data; and *2 A. Kimura and M. Nonaka, unpublished data

Fig. 3

Evolutionary conservation of genetic linkages between complement genes. Genomic organization of four sets of the linked complement genes in four species, human (Hosa), chicken (Gaga), clawed frog (Xetr), and fugu (Taru), are shown to scale: a C6 and C7, b C8A and C8B, c C1r and C1s, and d RCA genes. Note that the relative orientations of these genes are perfectly conserved except for the fish C1s gene

Fig. 4

Evolutionary processes of the complement system. Evolutionary origins of the three complement activation pathways are shown by the gray arrows. The origin and evolution of the major gene families of the complement system are shown by the colored arrows. Timings of the gene duplications that possibly contributed to the establishment of the classical pathway are shown by the double-headed arrows. Because the presence of the classical pathway was functionally demonstrated in sharks, it is likely that the Bf/C2 and MASP/C1r,s gene duplication occurred before the emergence of cartilaginous fish