Ancient divergence of a complex family of immune-type receptor genes

Abstract

Multigene families of activating/inhibitory receptors belonging to the immunoglobulin superfamily (IgSF) regulate immunological and other cell-cell interactions. A new family of such genes, termed modular domain immune-type receptors (MDIRs), has been identified in the clearnose skate (Raja eglanteria), a phylogenetically ancient vertebrate. At least five different major forms of predicted MDIR proteins are comprised of four different subfamilies of IgSF ectodomains of the intermediate (I)-or C2-set. The predicted number of individual IgSF ectodomains in MDIRs varies from one to six. MDIR1 contains a positively charged transmembrane residue and MDIR2 and MDIR3 each possesses at least one immunoreceptor tyrosine-based inhibitory motif in their cytoplasmic regions. MDIR4 and MDIR5 lack characteristic activating/inhibitory signalling motifs. MDIRs are encoded in a particularly large and complex multigene family. MDIR domains exhibit distant sequence similarity to mammalian CMRF-35-like molecules, polymeric immunoglobulin receptors, triggering receptors expressed on myeloid cells (TREMs), TREM-like transcripts, NKp44 and FcR homologs, as well as to sequences identified in several different vertebrate genomes. Phylogenetic analyses suggest that MDIRs are representative members of an extended family of IgSF genes that diverged before or very early in evolution of the vertebrates and subsequently came to occupy multiple, fully independent distributions in the present day.

The TREM-1/DAP12 pathway

“…Orthologues of TREM proteins have also been described in chickens, porcine, and bovine [27,28]. Furthermore, similar families designated modular domain immune-type receptors (MDIRs) and novel immunoglobulin-like transcripts (NILT) have been identified in skates [29], and carp [30], respectively, indicating that these families are in fact highly conserved in evolution. Since it is feasible that certain genes evolved under selective pressure for pathogen resistance, it will be important to investigate polymorphisms and variability of gene numbers within the TREM cluster and their association with infectious disease susceptibility.…”

The CD300 molecules regulate monocyte and dendritic cell functions

“…Cluster analysis suggests that the human family members have evolved in pairs; CD300a is most similar to CD300c, CD300b is most similar to CD300f and CD300d is most similar to CD300e. The CD300 Ig domain has evolved from an ancient Ig-like domain and related domains can be traced back to ancient vertebrates (Cannon et al 2006;Stet et al 2005). Orthologues for different CD300 genes have been found in mammals, birds and fish (Stet et al 2005;Viertlboeck et al 2006).…”

“…Orthologues for different CD300 genes have been found in mammals, birds and fish (Stet et al 2005;Viertlboeck et al 2006). CD300 molecules show the closest sequence similarity of any mammalian proteins to Modular Domain Immune type Receptors (MDIR) found in the clear nose skate (Raja eglanteria) (Cannon et al 2006). CD300g bears a close relationship with MDIR1 and the remaining MDIR2-4 molecules show greater similarity to CD300a-f.…”

Evolutionary constraint on Otx2 neuroectoderm enhancers-deep conservation from skate to mouse and unique divergence in teleost

“…To identify Otx2 genes in clear nose skate, R. eglanteria, and Indonesian coelacanth, L. menadoensis, a seminested degenerate PCR was performed for exon 3 as described (36) by using skate and coelacanth genomic DNA. The products thus obtained were verified by sequencing and used to screen BAC libraries of each species (37,38) to identify the BAC clones containing the Otx2 loci. Draft sequences of BAC clones were determined by shotgun sequence method; conserved motives among animals were determined by using VISTA and BLAST programs (8).…”