Genomic analysis of immunity in a Urochordate and the emergence of the vertebrate immune system: “waiting for Godot”

Abstract

Genome-wide sequence analysis in the invertebrate chordate, Ciona intestinalis, has provided a comprehensive picture of immune-related genes in an organism that occupies a key phylogenetic position in vertebrate evolution. The pivotal genes for adaptive immunity, such as the major histocompatibility complex (MHC) class I and II genes, T-cell receptors, or dimeric immunoglobulin molecules, have not been identified in the Ciona genome. Many genes involved in innate immunity have been identified, including complement components, Toll-like receptors, and the genes involved in intracellular signal transduction of immune responses, and show both expansion and unexpected diversity in comparison with the vertebrates. In addition, a number of genes were identified which predicted integral membrane proteins with extracellular C-type lectin or immunoglobulin domains and intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and immunoreceptor tyrosine-based activation motifs (ITAMs) (plus their associated signal transduction molecules), suggesting that activating and inhibitory receptors have an MHC-independent function and an early evolutionary origin. A crucial component of vertebrate adaptive immunity is somatic diversification, and the recombination activating genes (RAG) and activation-induced cytidine deaminase (AID) genes responsible for the Generation of diversity are not present in Ciona. However, there are key V regions, the essential feature of an immunoglobulin superfamily VC1-like core, and possible proto-MHC regions scattered throughout the genome waiting for Godot.

Genes “Waiting” for Recruitment by the Adaptive Immune System: The Insights from Amphioxus

“…Besides the genes encoding proteasome (proteasome, macropain) subunit ␤-type (PSMB)7/10 and PSMB5/8 previously reported (45,46), other homologues of the housekeeping genes PSMB6/9 and PA28␥ were also found in our library. Like the genes found in lamprey (6) and ascidian (12), amphioxus seems to have no inducible forms that change their expression pattern or even their biochemical behavior for Ag processing after genomic duplication. Homologues of the chaperones involved in the process of MHC I molecules assembly were identified in our library such as calreticulin, chaperone protein Dnak (Hsp70), and the glucose-regulated The selective expressions of VCP, KE2-like, and Amphi-CD53 in adult amphioxus were revealed by in situ hybridization in transverse sections.…”

“…Using the short-primer PCR, largely based on the conserved short motifs in the Ig-fold along with other methods (34), many genes bearing the typical V-C structures have been isolated (10,35,36) and most of them function as the receptors of innate immunity, suggesting the evolutionary relationship between innate immunity and adaptive immunity (37). Recently, some IgSF members bearing the V or V-C structures have been found in ascidian genome (12) and in amphioxus (10,11). The architecture of these genes showed more or less similarities to the Ag receptors and provided insights to the primitive forms of Ag binding receptors.…”

“…The following studies (14,15) showed more information about the relationship between this proto-MHC region and its human paralogous regions. The genomic analyses of ascidian also revealed the existence of the preduplicated form of proto-MHC region (12). Flajnik and Kasahara (16) compared the MHC regions of nonmammalian vertebrates and suggested that the ancient genome duplication played an important role in the origin of MHC region.…”

“…In addition, a multigene family containing Ig-like variable regions, V region-containing chitin-binding protein (VCBP), and an IgSF gene homologous to CD47 have been identified in the intestine of amphioxus (10,11). The genomic draft of a urochordate, Ciona intestinalis, demonstrated the existence of many homologues of the genes involved in immune system especially innate immunity (12). These studies suggested that some possible ancestors of the molecules involved in the adaptive immunity existed in the early chordates.…”

Characterization of bbtTICAM from amphioxus suggests the emergence of a MyD88-independent pathway in basal chordates

“…There are two MyD88-like proteins and two atypical TLRs in Hydra [8], one MyD88 homolog and one TLR-1-like protein in Nematostella [8], four MyD88-like and more than two hundred TLRs in the sea urchin [10,11], and one MyD88 ortholog and three TLRs in Ciona [45]. The identification of both TLR and MyD88 in different evolutionary stages and the functional interaction of amphioxus TLR with MyD88 [13] suggest that the MyD88-dependent pathway is conserved and crucial for invertebrate TLR signaling in detecting invading pathogens.…”