Sequence Analysis of MHC Class II Genes in Cetaceans

Abstract

Genes of the major histocompatibility complex (MHC) offer several assets that make them unique candidates for studies of adaptation in natural populations (Potts & Wakeland, 1990; Hedrick, 1994). The primary role of the MHC is to recognize foreign proteins, present them to specialist immune cells and initiate an immune response (Klein & Figueroa, 1986). The MHC gene family includes highly polymorphic genes encoding a set of transmembrane glycoproteins that are critical to the generation of immune responses (Kennedy et al., 2002). In general, foreign proteins enter cells either by infection or by phagocytosis into antigenpresenting cells such as macrophages. These foreign proteins are broken down into small peptides and loaded onto specific MHC molecules. The MHC molecule comprises an immunoglobulin stalk, which anchors the molecule to the cell surface, and a basket receptor called antigen-recognizing sites (ARS) located in peptide binding region (PBR). A subset of these protein/MHC complexes are then transported to the cell surface and presented for interrogation by the circulating T-cell population. A complex cascade of immune responses is triggered when the T cell binds to the presented peptide. Two major groups of MHC genes can be distinguished. MHC class I genes play an essential role in the immune defense against intracellular pathogens by binding peptides mainly derived from viral proteins and cancer-infected cells. They are expressed on the surface of all nucleated somatic cells. In contrast, MHC class II genes are predominantly involved in monitoring the extracellular environment by presenting peptides mainly derived from parasites (e.g. bacteria, nematodes, cestodes) to the T-cells. They are primarily expressed on antigen-presenting cells of the immune system, such as B cells and macrophages. Although ARS do show a degree of specificity, a single MHC molecule can bind multiple peptides that have common amino acids at particular anchor positions (Altuvia & Margalit, 2004). Genes within the MHC involved in antigen presentation constitute the most polymorphic loci known in vertebrates (Hedrick, 1994). The polymorphism of the MHC-molecules is associated with the diversity of the T-lymphocyte receptors that in turn determine the disease and parasite resistance of an organism and thus may affect the long-term survival rate of populations (Hedrick et al., 1999; Paterson et al., 1998). The ARS show high levels of polymorphism not only in the number of alleles but also in the sequence variation among alleles (Hughes & Yeager, 1998). The general view is that balancing selection is the determinant role in shaping patterns of nucleotide diversity in MHC genes (Bernatchez & Landry, 2003; Hughes & Nei, 1989).