Genomic insights into the immune system of the sea urchin

Abstract

Comparative analysis of the sea urchin genome has broad implications for the primitive state of deuterostome host defense and the genetic underpinnings of immunity in vertebrates. The sea urchin has an unprecedented complexity of innate immune recognition receptors relative to other animal species yet characterized. These receptor genes include a vast repertoire of 222 Toll-like receptors, a superfamily of more than 200 NACHT domain-leucine-rich repeat proteins (similar to nucleotide-binding and oligomerization domain (NOD) and NALP proteins of vertebrates), and a large family of scavenger receptor cysteine-rich proteins. More typical numbers of genes encode other immune recognition factors. Homologs of important immune and hematopoietic regulators, many of which have previously been identified only from chordates, as well as genes that are critical in adaptive immunity of jawed vertebrates, also are present. The findings serve to underscore the dynamic utilization of receptors and the complexity of immune recognition that may be basal for deuterostomes and predicts features of the ancestral bilaterian form.

Fig. 1

A simplified phylogenetic tree depicting the general relationships of the major bilaterian phyla and chordate subphyla, highlighting select species that use different somatic mechanisms of immune receptor diversification. Red dots designate animal groups where the vast majority of immune data have been derived. Solid black dots denote taxa in which species have been the subject of extensive molecular immune research. Circles denote phyla where some molecular data are available. Color variation (see key) over specific phyla denotes the presence of a major somatic mechanism of receptor diversification in at least one representative member (6) and is not intended to be mutually exclusive. In the case of somatic variation, shade intensity indicates the level of empirically established diversity. Innate immune receptors, including TLRs, are likely present in all of the phyla. Numbers given beside taxa names are approximate estimates of species diversity and are presented to underscore the immense variety of immune mechanisms that have not yet been investigated [primarily taken from the Tree of Life Web project (44)]. Cnidarians (e.g., jellyfishes and sea anemones) are shown as an outgroup to the Bilateria. This view is not intended to represent all known species in which immune-type mediators have been identified.

Fig. 2

Innate immune receptor multiplicity in the sea urchin genome sequence. (A) Comparison of gene families encoding innate immune receptors in representative animals with sequenced genomes to S. purpuratus (bold, hereafter designated sea urchin). For some key receptor classes, gene numbers in the sea urchin exceed those of other animals by more than an order of magnitude. Representative animals are Homo sapiens, H.s.; C. intestinalis, C.i.; S. purpuratus, S.p.; D. melanogaster, D.m.; and C. elegans, C.e. Gene families include TLRs, NLRs, SRCRs, PGRPs, and GNBPs. Specifically, TLR diagrams show V, vertebrate-like, P, protostome-like; and S, short type; oval indicates TIR domain; and segmented partial circles indicate LRR regions; LRR-NT, blue; and LRR-CT, red. NLR diagram shows death family domain in pink, NACHT domain in yellow, and the LRR region, for which horizontal orientation implies cytoplasmic function. The other diagrams show multiple SRCR genes (both secreted and transmembrane), PGRP genes (PFAM: Amidase_2 domain–containing, secreted or transmembrane); and GNBP proteins (PFAM: Glyco_hydro_16–containing, secreted). For multiple SRCR genes, representative values are domain number (gene number in parentheses). For C. intestinalis, numbers correspond to all annotated SRCR proteins. Phylogenetic relations among species are indicated by the red cladogram at the left of the table; diagrams of molecules are not intended to imply specific structural features. (B) Unrooted neighbor-joining tree showing interrelations of TIR domains of TLRs in sea urchin. TLRs can be classified into three divergent classes (protostome-like, intron-containing, and short) and a large sea urchin lineage-specific family, which distributes into seven (I to VII) subgroups; numbers of member genes indicated in circles. Group I can be further subdivided [I(A) to I(E)]. Numbers beside branches indicate % bootstrap support for each subgroup. Efforts to relate vertebrate and other TLRs to the sea urchin genes result in low-confidence affinities with the divergent groups as described for other TLR comparisons (24). (C) Clustering of representative sea urchin TLR genes (yellow arrows) from high-confidence regions of the assembly supported by bacterial artificial chromosome (BAC) sequence (indicated by blue bar). Clusters segregate according to groups [I(B) and I(C) are subgroups of group I]. Gene model numbers are indicated above arrows. Model numbers with asterisks are close matches to annotated gene models and likely represent the second haplotype to that which was used to create models from the previous assembly. Red arrows indicate non-TLR genes. V indicates putative position of a V-type immunoglobulin domain cluster. Verification of cluster organization will require further independent genomic analysis. ψ signifies pseudogene. Scale is indicated in kb (kilobase pairs).