Characterization of the opossum immune genome provides insights into the evolution of the mammalian immune system

Abstract

The availability of the first marsupial genome sequence has allowed us to characterize the immunome of the gray short-tailed opossum (Monodelphis domestica). Here we report the identification of key immune genes, including the highly divergent chemokines, defensins, cathelicidins, and Natural Killer cell receptors. It appears that the increase in complexity of the mammalian immune system occurred prior to the divergence of the marsupial and eutherian lineages approximately 180 million years ago. Genomes of ancestral mammals most likely contained all of the key mammalian immune gene families, with evolution on different continents, in the presence of different pathogens leading to lineage specific expansions and contractions, resulting in some minor differences in gene number and composition between different mammalian lineages. Gene expansion and extensive heterogeneity in opossum antimicrobial peptide genes may have evolved as a consequence of the newborn young needing to survive without an adaptive immune system in a pathogen laden environment. Given the similarities in the genomic architecture of the marsupial and eutherian immune systems, we propose that marsupials are ideal model organisms for the study of developmental immunology.

Figure 1.

Chromosome map showing locations of immune gene clusters in the opossum. Locations of key immune gene clusters are shown.

Figure 2.

Phylogenetic tree of mammalian cathelicidin genes.

Figure 3.

Synteny map of mammalian alpha- and beta-defensin gene clusters (modified from Patil et al. 2005). Four different beta-defensin clusters (A, B, C, D) are found in rat, mouse, and dog. Five clusters are found in humans due to a split in cluster D. The opossum contains three clusters suggesting that eutherian clusters B and C evolved from a single cluster in ancestral mammals. The alpha-defensins (cluster A) are denoted by rectangles. Arrows show transcriptional orientation. Pseudogenes are shown in white, and putative functional genes in black. Orthologs, based on phylogenetic analyses, are connected.

Figure 4.

Comparative map showing opossum and eutherian NKC gene organization (modified from Hao et al. 2006). Arrows show transcriptional orientation. Pseudogenes are shown in white and putative functional genes in black.

Figure 5.

Manual curation of opossum LRC Ig-like domains to predict MAIR Ig domain structure. Domains are colored based on their location on the phylogenetic tree in Supplemental Figure 9.