Modo-UG, a marsupial nonclassical MHC class I locus

Authors: GOUIN, NICOLAS - SAN ANTONIO, TEXAS; WRIGHT, APRIL - U NEW MEXICO; Miska, Kate; PARRA, ZULY - U NEW MEXICO; SAMOLLOW, PAUL - TEXAS A&M UNIV; BAKER, MICHELLE - U NEW MEXICO; MILLER, ROBERT - U NEW MEXICO

Submitted to: Immunogenetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/22/2006
Publication Date: 6/1/2006
Citation: Gouin, N., Wright, A.M., Miska, K.B., Parra, Z.E., Samollow, P.B., Baker, M.L., Miller, R.D. 2006. Modo-UG, a marsupial nonclassical MHC class I locus. Immunogenetics. 58:5-6.

Interpretive Summary: All living mammals are currently divided into three major groups, 1) the eutherians, like humans and mice, that give birth to live young, 2) the marsupials, like opossums and kangaroos, give birth to under-developed young which then complete their development outside of the mother, many times in a pouch, and 3). monotremes which lay eggs. Very little is known about the immunology of marsupials. In order to expand our knowledge of molecules with immune function a study was initiated investigating the presence of non-classical tissue transplant antigens in the opossum. Tissue transplant antigens are referred to as Major Histocompatibility Complex Class I (Mhc-I) molecules and in addition to governing tissue compatibility they protect us from viral infections. Non-classical Mhc-I molecules have evolved to carry out specific functions, such as transportation of antibodies across the placentas. It is important to study the evolution of non-classical Mhc-I molecules in many different species, since it helps us understand the complexity of the immune system and recognize which of its components is present in which species, thus helping us understand its evolution. This study describes the first isolation and characterization of non-classical Mhc-I genes in the opossum. Upon analysis, it was clear that although these molecules are very similar to those found in humans and mice, they have evolved independently. Additionally, several different forms of non-classical Mhc-I molecules are present in the opossum, and their genetic variability is very low, making these newly discovered molecules similar in character to those from eutherian mammals.

Technical Abstract: Modo-UG is a class I gene located in the MHC of the marsupial Monodelphis domestica, the gray short-tailed opossum. Modo-UG is expressed as three alternatively spliced mRNA forms, all of which encode a transmembrane form with a short cytoplasmic tail that lacks phosphorylation sites typically found in classical class I molecules. The three alternative mRNAs would encode, a full-length form, an isoform lacking the alpha 2 domain, and one lacking both the alpha 2 and alpha 3 domains. Genotyping both captive bred and wild M. domestica from different geographic regions revealed no variation in the residues that make up Modo-UG’s peptide binding groove. Modo-UG’s low polymorphism is contrasting to that of a nearby class I locus, Modo-UA1, which has a highly polymorphic peptide-binding region. Absence of functional polymorphism in Modo-UG is therefore not a general feature of opossum class I genes but the result of negative selection. Modo-UG is the first MHC linked marsupial class I to be described that appears to clearly have non-classical features.