Diversification of innate immune genes: lessons from the purple sea urchin

Abstract

Pathogen diversification can alter infection virulence, which in turn drives the evolution of host immune diversification, resulting in countermeasures for survival in this arms race. Somatic recombination of the immunoglobulin gene family members is a very effective mechanism to diversify antibodies and T-cell receptors that function in the adaptive immune system. Although mechanisms to diversify innate immune genes are not clearly understood, a seemingly unlikely source for insight into innate immune diversification may be derived from the purple sea urchin, which has recently had its genome sequenced and annotated. Although there are many differences, some characteristics of the sea urchin make for a useful tool to understand the human immune system. The sea urchin is phylogenetically related to humans although, as a group, sea urchins are evolutionarily much older than mammals. Humans require both adaptive and innate immune responses to survive immune challenges, whereas sea urchins only require innate immune functions. Genes that function in immunity tend to be members of families, and the sea urchin has several innate immune gene families. One of these is the Sp185/333 gene family with about 50 clustered members that encode a diverse array of putative immune response proteins. Understanding gene diversification in the Sp185/333 family in the sea urchin may illuminate new mechanisms of diversification that could apply to gene families that function in innate immunity in humans, such as the killer immunoglobulin-like receptor genes.

Short tandem repeats, segmental duplications, gene deletion, and genomic instability in a rapidly diversified immune gene family

“…This is evident from the KIR gene family, which is tightly clustered and shows variations in gene copy numbers for different human haplotypes in addition to sequence diversity in the population based on 15 to 112 alleles for different loci [9]. Variations in the KIR region is thought to result from genomic instability driven by shared sequences within and surrounding the genes, including minisatellite sequences in the first intron, all of which can lead to crossing over among the tandemly arranged genes, expansion and contraction of gene numbers from meiotic mispairing, in addition to recombination, gene conversion, domain shuffling, duplications and deletions and single nucleotide polymorphisms ([45, 46], reviewed in [47, 48]). Similar to the assembly problems for the Sp185/333 gene family, the attributes of the KIR family have also resulted in very poor assembly in macaque genome sequences [49].…”

TheSp185/333immune response genes and proteins are expressed in cells dispersed within all major organs of the adult purple sea urchin

“…The extraordinary sequence diversity of the encoded proteins is likely a reflection of the arms race between host and pathogen. 59,60 Sea urchins are in constant contact with microbes that share their seawater and ocean substrate habitat. 61 Infection from this constant exposure to microbes is likely held in check by a variety of immune mechanisms, including the activities of the coelomocytes and the sequence diversity that is present a variety of the sea urchin immune gene families, 1,2,4,5 including the Sp185/333 genes.…”

Sea urchin immune cells as sentinels of environmental stress

“…To fight different pathogens, the sea urchin has generated a random diversification and expansion of PRRs, perhaps by gene recombination and/or gene duplication/deletion mechanisms generating receptor gene sequence diversity resulting from a constant, long-term evolutionary competition between high rates of mutation and/or variation in antigens (Smith, 2010). Three classes of innate receptor proteins are particularly expanded in the sea urchin genome, which comprise vast families of TLRs, leucine-rich repeat (LRR) domain-containing proteins similar to the vertebrate NOD/NALP receptors (NLRs) and scavenger receptor cysteine-rich domains (SRCRs) .…”