Origin of Metazoan Adhesion Molecules and Immune System: Prerequisites for Multicellularity

Werner E.G. MUELLER Institut fuer Physiologische Chemie, Abteilung Angewandte Molekularbiologie, Universitaet, Duesbergweg 6, D-55099 Mainz; GERMANY tel.: +6131-395910; fax.: +6131-395243; e-mail: WMUELLER@mail.UNI-Mainz.DE.

The phylogenetic relationships of the kingdom Animalia (Metazoa) have long been questioned. Focusing on the lowest eukaryotic multicellular organisms, the metazoan phylum Porifera (sponges), it remained unclear if they independently evolved multicellularity from a separate protist lineage (polyphyly of animals) or derived from the same protist group as the other animal phyla (monophyly). Based on constituent characters of the sponges a monophyletic origin of the Porifera can be deduced. After having analyzed those genes from the sponge Geodia cydonium which are typical for multicellularity, e.g. those coding for adhesion molecules/receptors and a nuclear receptor, it has to be concluded that all animals, including sponges, are of monophyletic origin. In addition it was estimated that the adhesion molecules/receptors from sponges diverged from a common ancestor in the Precambrian (### 800 Myrs ago).

Recently, we could demonstrate that sponges possess molecules that are similar in structure to those molecules involved in the immune system in mammals. Experiments with the marine sponges Geodia cydonium and Suberites domuncula have been performed on tissue (auto- and allografting) as well as on a cellular level. The studies revealed that sponges are provided with elements of the mammalian innate immune system, such as molecules containing scavenger receptor cysteine-rich domains. Furthermore, macrophage-derived cytokine-like molecules have been identified which are upregulated during the grafting process. In addition, the (2'-5')oligoadenylate synthetase system exists in sponges. "Precursors" of the second type of immune response in mammals, the adaptive immune system, have been traced in sponges. It is shown that the expression of a lymphocyte-derived cytokine from mammals is upregulated during non-self recognition in S. domuncula. Finally, in G. cydonium two classes of receptors which comprise Ig-like domains have been identified; the receptor tyrosine kinases and the non-enzymic sponge adhesion molecules. They contain two polymorphic Ig-like domains that are grouped to the variable set of immunoglobulins. The expression of these molecules is also upregulated during the grafting process. It is concluded that sponges are already provided with a series of elements used in higher vertebrates for both the innate and the adaptive immune recognition.

REFERENCES W.E.G. Mueller: Molecular Phylogeny of Metazoa [Animals]: Monophyletic Origin. Naturwiss. 82, 321-329 (1995).

W. Wimmer, S. Perovic, M. Kruse, A. Krasko, R. Batel and W.E.G. Mueller: Origin of the Integrin-mediated Signal Transduction: Functional Studies with Cell Cultures fromthe Sponge Suberites domuncula. Europ. J. Biochem. 260, 156-165 (1999).

W.E.G. Mueller, B. Blumbach and I.M. Mueller: Evolution of the Innate and Adaptive Immune Systems: Relationships Between potential Immune molecules in the Lowest Metazoan Phylum [Porifera] and Those in Vertebrates. Transplantation, in press