Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jun 22;20(12):1122-7.
doi: 10.1016/j.cub.2010.04.050. Epub 2010 May 27.

Hydractinia Allodeterminant alr1 Resides in an Immunoglobulin Superfamily-Like Gene Complex

Affiliations
Free PMC article

Hydractinia Allodeterminant alr1 Resides in an Immunoglobulin Superfamily-Like Gene Complex

Sabrina F P Rosa et al. Curr Biol. .
Free PMC article

Abstract

Allorecognition, the ability to discriminate between self and nonself, is ubiquitous among colonial metazoans and widespread among aclonal taxa. Genetic models for the study of allorecognition have been developed in the jawed vertebrates, invertebrate chordate Botryllus, and cnidarian Hydractinia. In Botryllus, two genes contribute to the histocompatibility response, FuHC and fester. In the cnidarian Hydractinia, one of the two known allorecognition loci, alr2, has been isolated, and a second linked locus, alr1, has been mapped to the same chromosomal region, called the allorecognition complex (ARC). Here we isolate alr1 by positional cloning and report it to encode a transmembrane receptor protein with two hypervariable extracellular regions similar to immunoglobulin (Ig)-like domains. Variation in the extracellular domain largely predicts fusibility within and between laboratory strains and wild-type isolates. alr1 was found embedded in a family of immunoglobulin superfamily (IgSF)-like genes, thus establishing that the ARC histocompatibility complex is an invertebrate IgSF-like gene complex.

Figures

Figure 1
Figure 1
Positional cloning of alr1 (A) Genetic map of the Hydractinia allorecognition complex (ARC). The alr1 minimum tiling path was distributed over four BAC clones (heavy lines). (B) Physical map of the genomic alr1 interval (ARC-f haplotype). Breakpoints are designated as X’s. BAC end markers are in red, markers designed to map the recombination breakpoints are in black. Markers 194s1 and 194c28 define the 300.8 kb minimum alr1 interval. (C) Predicted coding sequences in the alr1-f interval (see also Table S1 and Figure S1). Boxes above and below the line represent predicted genes on the plus and minus strand, respectively. Boxes numbered 1, 4 and 7 represent coding sequences bearing sequence similarity to Ig-like domains (see text and Figure S2). (D) Genomic organization of CDS4. White boxes, black boxes and bent lines represent UTRs, exons and introns, respectively. (E) Alignment of the CDS4 ARC-f and –r amino acid sequences. Polymorphic residues are shown in red. Domain organization of the predicted CDS4 protein is shown within colored boxes. SP, signal peptide; domains I and II, non-canonical Ig-like domains; TM, transmembrane domain; SH2, ITAM-like and SH3 sites, potential signal transduction motifs. The light yellow box indicates the segment of exon 4 missing in alternatively spliced variants. Exon organization is shown below the alignment. < and > indicate amino acids encoded by the last and first complete codon of the exon, respectively, and ^ indicates a codon spanning two exons.
Figure 2
Figure 2
CDS4 sequence variation. (A) Distribution of variability in 20 CDS4 alleles. (see also Figure S4). Per-site sequence variability was estimated using the Shannon Diversity Index (Shannon Entropy [25]), H′). H′ ranges from 0 (only one amino acid type is present at one site) to 4.322 (the 20 amino acids are present at one site). CDS4 domains are shown below the plot (see Figure 1D). Grey boxes represent regions where reliable alignments could not be generated. (B) Distribution of synonymous and non-synonymous mutations. The per-site difference between the number of non-synonymous mutations (dN) and synonymous mutations (dS) is shown along the Y-axis and was measured as LN (Bayes factor [dN > dS]) using the REL method available in the HyPhy statistical package [33]. Red lines indicate the 11 sites predicted to be under positive selection by at least two of the three methods (see also Table S3).
Figure 3
Figure 3
IgSF-like gene complex. Coding sequences showing sequence similarity to Ig-like domains in a 1.3 Mb region including the alr1-f interval. Orange boxes represent regions bearing similarity to V-set Ig-like domains and blue boxes to I-set Ig-like domains. Letters and numbers represent the IgSF-like genes identified outside and within the alr1-containing interval, respectively. Light orange boxes are regions that showed similarity to Ig V-set domains but that were not predicted as belonging to a coding sequence. * and indicate pCDS’s whose extracellular domains were polymorphic and monomorphic between the two laboratory haplotypes, respectively. Markers 194c1 and 194c10 represent the ends of the chromosome walk. Markers 194s1 and 194c28 represent the alr1 interval limits.
Figure 4
Figure 4
Pairwise comparisons between extracellular domains I (A) and II (B) of alr1 alleles and IgSF-like gene complex members. Rows contain CDS4 (alr1) alleles. Columns contain IgSF-like gene complex members from the ARC-f haplotype. “x” and “y” as designated in Figure 3. Colored squares represent the percentage amino acid similarity as indicated by the legend.

Similar articles

See all similar articles

Cited by 18 articles

See all "Cited by" articles

Publication types

Substances

Associated data

Feedback