Genome complexity in the coelacanth is reflected in its adaptive immune system

Abstract

We have analyzed the available genome and transcriptome resources from the coelacanth in order to characterize genes involved in adaptive immunity. Two highly distinctive IgW-encoding loci have been identified that exhibit a unique genomic organization, including a multiplicity of tandemly repeated constant region exons. The overall organization of the IgW loci precludes typical heavy chain class switching. A locus encoding IgM could not be identified either computationally or by using several different experimental strategies. Four distinct sets of genes encoding Ig light chains were identified. This includes a variant sigma-type Ig light chain previously identified only in cartilaginous fishes and which is now provisionally denoted sigma-2. Genes encoding α/β and γ/δ T-cell receptors, and CD3, CD4 and CD8 co-receptors also were characterized. Ig heavy chain variable region genes and TCR components are interspersed within the TCR α/δ locus; this organization previously was reported only in tetrapods and raises questions regarding evolution and functional cooption of genes encoding variable regions. The composition, organization and syntenic conservation of the major histocompatibility complex locus have been characterized. We also identified large numbers of genes encoding cytokines and their receptors, and other genes associated with adaptive immunity. In terms of sequence identity and organization, the adaptive immune genes of the coelacanth more closely resemble orthologous genes in tetrapods than those in teleost fishes, consistent with current phylogenomic interpretations. Overall, the work reported described herein highlights the complexity inherent in the coelacanth genome and provides a rich catalog of immune genes for future investigations.

A cold-blooded view of adaptive immunity

“…Subsequently, the IgD gene was uncovered in the genomic database of the amphibian genus Xenopus and shown to be expressed, like in mammals, via alternative splicing of IgM and IgD mRNA in naive B cells 50,53 . The cartilaginous fish homologue of IgD, IgW 54,55 , was also found in lungfish 56 , and in coelacanths, it seems to be the major isotype, with this famous species having lost IgM 57,58 . Recent data in bony fish and humans suggest that IgD is involved in inflammatory responses, binding to an unknown Fc receptor on basophils 59,60 .…”

Fish Immunoglobulins

“…IgW, which was first discovered in skates [45,46,47], later in shark [48,49], and then coelacanth [50,51], has gone by many names (IgX, IgNARC or IgR) before being proposed as an ortholog of IgD [29]. Nearly 500 MYA in the first jawed vertebrates IgM and IgW evolved in a relatively short period of time [32].…”

“…The σ-2 isotype (formerly known as σ-cart) was recently identified in the coelacanth. As no λ5 or VpreB surrogate light chain components have been found in fish, it remains to be seen how ordered chain rearrangement and testing is conducted and allelic exclusion maintained [26,51]. …”

“…These exons are followed by four tandem duplications of (Cω3-Cω4-Cω5) and two exons encoding the TM. The adaptive immune genes sequence identity of coelacanth more resembles that in tetrapod rather than teleost [51]. …”

Immunoglobulin light chain (IGL) genes in torafugu: Genomic organization and identification of a third teleost IGL isotype

“…It has long been known that mammals have two distinct IGL isotypes called kappa (κ) and lambda (λ), but additional IGL isotypes have been described in other vertebrate groups. The current classification system groups all vertebrate IGLs into four main ancestral branches: kappa (mammalian κ, elasmobranch type III/NS4, teleost L1/L3/F/G, Xenopus ρ), lambda (mammalian λ, elasmobranch type II/NS3), sigma ( Xenopus σ, teleost L2, elasmobranch type IV), and sigma-2 (elasmobranch type I/NS5, variant sigma-type in coelacanth)1011.…”