Reconstructing an Ancestral Mammalian Immune Supercomplex from a Marsupial Major Histocompatibility Complex

Abstract

The first sequenced marsupial genome promises to reveal unparalleled insights into mammalian evolution. We have used theMonodelphis domestica (gray short-tailed opossum) sequence to construct the first map of a marsupial major histocompatibility complex (MHC). The MHC is the most gene-dense region of the mammalian genome and is critical to immunity and reproductive success. The marsupial MHC bridges the phylogenetic gap between the complex MHC of eutherian mammals and the minimal essential MHC of birds. Here we show that the opossum MHC is gene dense and complex, as in humans, but shares more organizational features with non-mammals. The Class I genes have amplified within the Class II region, resulting in a unique Class I/II region. We present a model of the organization of the MHC in ancestral mammals and its elaboration during mammalian evolution. The opossum genome, together with other extant genomes, reveals the existence of an ancestral “immune supercomplex” that contained genes of both types of natural killer receptors together with antigen processing genes and MHC genes.

Extended Gene Map Reveals Tripartite Motif, C-Type Lectin, and Ig Superfamily Type Genes within a Subregion of the Chicken MHC-B Affecting Infectious Disease

“…Overall, the organization of MHC genes in the chicken and the quail is consistent with recent models of the MHC evolving first as a protocomplex containing genes involved in innate immunity (35,52) and with the rapid evolution of gene-encoding receptors and ligands for innate and adaptive immune cell interactions. Furthermore, the similarities between the chicken B (and Y) C-type lectin-like genes and sequences present within the genomes of avian pathogens are striking (M. M. Miller, unpublished data).…”

The dominantly expressed class I molecule of the chicken MHC is explained by coevolution with the polymorphic peptide transporter (TAP) genes

“…[28][29][30][31]. Indeed, the same features are found in at least one marsupial (32), so it would appear that genomic rearrangements occurred in the lineage leading to the placental mammals, most likely an inversion bringing the class III region in between the class I and class II regions, with the class I antigen processing genes (TAPs, tapasin, and inducible proteasome components) left behind in the class II region (10,11). However, secondary evolutionary changes may also have taken place in some placental mammals, as seems clear for the rat.…”

Low major histocompatibility complex diversity in the Tasmanian devil predates European settlement and may explain susceptibility to disease epidemics

“…MHC proteins are present on the surface of most cells, and are critical in immune recognition of pathogens and foreign or infected cells. Devil class I sequences show 88.5 per cent average nucleotide identity [14] compared with grey short-tailed opossum (Monodelphis domestica) sequences that exhibit between 49 and 83 per cent identity [15]. The lack of MHC diversity in Tasmanian devils may have facilitated the spread of the most recent disease epidemic, the devil facial tumour disease (DFTD) [12].…”