ISJ 12: 170-172, 2015 ISJ 12: 170-172, 2015 ISSN 1824-307X LETTER TO EDITOR Conserved histocompatible machinery in marine invertebrates? B Rinkevich Israel Oceanography & Limnological Research, National Institute of Oceanography, Tel Shikmona, PO Box 8030, Haifa 31080, Israel Accepted May 26, 2015 To the Editor How would we best inquire the challenging query for the likely shared allorecognition properties between taxonomically distant marine invertebrates? Are the customary comparisons made with the mammalian immune systems satisfactory? The below discussion challenges this routinely employed research approach. As organismal genetic-homogeneity is assumed to be evolutionary beneficial in preventing inner- organism conflicts (Dawkins, 1990; Pal and Papp, 2000), numerous natural and experimental transplantation situations have spawned considerable interest in the evolution of allorecognition, the non-pathogenically directed property of immunity (Stewart, 1992; De Boer, 1995; Rinkevich, 1999). Therefore, it has been proposed that preserving ‘individuality’ from soma and the germline littering by conspecific alien cells might have been the primeval function of the immune system, a theory that sees allorecognition as the possible key common background on which the diverse immunity has been developed (Magor et al., 1999; Rinkevich, 1999, 2012). Following the aforementioned rationale, and if preservation of the individual identity was the original and salient function of the primitive immune system before it was harnessed to defend from invasive pathogens, we may expect to find intimate linkages between the allorecognition machineries in various phyla of multicellular organisms (Grosberg, 1988). Indeed, allorecognition phenomena exhibit suites of effector mechanisms, are ubiquitously recorded in diverse taxa of marine sedentary invertebrates, including sponges, cnidarians, bryozoans and urochordates, and are frequently documented in the field following direct tissue contacts between conspecifics (e.g., Oka and Watanabe, 1960; Hildemann, 1979; Rinkevich, 1999, 2002; Cima et al., 2004; Hughes et al., 2004; Cerrano et al., 2007; Fernàndez-Busquets, 2008). These tissue-to-tissue contacts beget surprisingly complex sets of allorecognition phenomena, typified ___________________________________________________________________________ Corresponding author: Buki Rinkevich Israel Oceanography & Limnological Research National Institute of Oceanography Tel Shikmona, PO Box 8030, Haifa 31080, Israel E-mail: buki@ocean.org.il by extreme allotypic diversity, a wide range of effector arms (many of which are simultaneously used for other purposes, such as feeding and competition; Williams, 1991; Rinkevich, 2011), allogeneic maturation, highly tuned immunological specificity, quasi-immunological memory, alloincompatible necrotic zones and fusion events that lead to chimerism (reviewed in Oka and Watanabe, 1960; Grosberg, 1988; Leddy and Green, 1991; Rinkevich 1996a, b, 1999, 2002, 2004, 2011; Gaino et al., 1999; Cima et al., 2004; Cerrano et al., 2007). The genetics of allorecognition in marine invertebrates were elucidated in two model systems, the hydrozoan Hydractinia symbiolongicarpus (Cadavid et al., 2004; Nicotra et al., 2009) and the colonial urochordate Botryllus schlosseri (Sabbadin et al., 1992; Rinkevich, 1993; Voskoboynik et al., 2013a). While the commonalities of allorecognition phenomena are above dispute (Loker et al., 2004), the evolutionary basis for the effector mechanisms is not easily understood or illustrated yet. Many of the related evolutionary claims, which are based on the striking superficial similarities between some genes and processes in marine invertebrates, are based on the claimed erroneous notion, that vertebrate immunity and marine invertebrate allorecognition are homologous, ‘stemming from the rationale that the early appearance of host defense indicates that same immune constituents are shared by most multicellular organisms; a sort of anthropocentrism’ (Rinkevich, 2011). Also, synthetic comparisons of marine invertebrates’ genes with seemingly counterpart vertebrate immune genes (the common approach taken by scientists) result in very limited valid information regarding the nature of allorecognition in marine invertebrates, as does the employment of deduced genomic sequences or gene homology comparisons (Loker, 2004; Rinkevich, 2011, 2012). The same holds true when the comparisons are made on the cellular level (Peddie and Smith, 1995; Ballarin et al., 2001; Khalturin et al., 2003; Dunn, 2009). The literature thus reveals that we still do not really know what allorecognition in marine invertebrates is. As complex as allorecognition phenomena in marine invertebrates are, the historecognition attributes that accept/reject alien tissues are probably not associated with host-parasitic and disease 170   mailto:buki@ocean.org.il responses; thus host-parasitic/disease events (that are customary compared with the mammalian immune systems) have emerged as a serious obstacle to elucidating the nature of allorecognition (Rinkevich, 2012). Based on the aforementioned, we may re- examine the following query: Are the salient properties of allorecognition systems in marine invertebrates conserved and thus shared by unalike taxa? This would be best summoned by analyzing allorecognition in one of the most morphologically simplest extant metazoans that do not possess a circulatory system (e.g., Cnidarians; Dunn, 1999) and comparing the results with results from one of the most developed metazoan groups that has a circulatory system operating in self/non-self recognition (e.g., colonial Urochordates; Rinkevich, 2002). Both groups present copious in situ documentations for allogeneic and xenogeneic encounters. As the cellular components of allorecognition in both phyla are clearly dissimilar (e.g., the nematocysts in cnidarians and the morula cells in the tunicates; Rinkevich et al., 1998; Dunn, 1999; Ballarin et al., 2001; Rinkevich, 2012), it is advisable to establish cross-phyla comparisons at the molecular constituents that actually manifest allorecognition responses (in lieu of molecular comparisons with lists of mammalian immune related genes). This approach is further eased by the recent development in genome sequences in marine cnidarians and urochordates (e.g., Rast and Messier-Solek, 2008; Steele et al., 2011; Voskoboynik et al., 2013b). A recent study (Oren et al., 2013) illuminates the scientific insight that surfaced when employing the cross-invertebrate phyla comparisons approach and the need for additional, similar studies. Oren et al. (2013) compared two independently developed allogeneic rejection transcriptomes, one from incompatible challenged colonies of the stony coral Stylophora pistillata and the other from allo-rejecting partners of the ascidian B. schlosseri. This revealed common expression patterns of specific immune- related genes and shared functional attributes expressed during allogeneic rejection. Oren et al. (2013) disclosed 74 similar blast matches in the immune-related categories of the coral and the ascidian expression libraries, accounting for 37.2 % of the total immunerelated matches. Within these matches, 43/74 cases were exact matches. Two highly noticeable genes within this shared list of expressed genes were the immunophilins, Cyclophilin A (CypA) and the FK506-binding protein (FKBP). The mRNA expressions of the coral and ascidian immunophilins in allorecognition challenged colonies were restricted to the specific effector cell populations (nematoblasts and nematocytes in the coral and morula cells in the ascidian). Furthermore, gene expressions were limited to only some of the effector cells within a population, disclosing disparities in numbers and location between naïve and immune challenged colonies. Administration of the immunosuppression drug Cyclosporine-A during ascidian allogeneic interactions inhibited both the fusion and the rejection reactions, probably through the inhibition of the ascidian morula cells’ movement and activation. The results of Oren et al. 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