The genetic code of marsupials has now been documented for the first time. An international team led by Kathy Belov from the University of Sydney's Faculty of Veterinary Science published an analysis of the marsupial genome in the open access journal PLoS Biology. The paper details the evolution of an important cluster of immune genes known as the MHC using available genome sequences of the gray, short-tailed opossum (Monodelphis domestica), a marsupial found in South America.
"Mapping the opossum MHC has allowed us to deduce what the MHC of ancestral mammals looked like," says Belov. "We think it contained several different types of immune genes in a single complex. These genes are no longer found in a single complex in any living animal but are scattered over various chromosomes. We have named this complex 'The Immune Supercomplex.'"
Belov et al. found that while the size and complexity of the opossum MHC is closer to eutherian (placental) mammals, its organization is closer to fish and birds. "The clues we unearthed by looking at different genomes are also helping us to understand how our own intricate immune system evolved from the relatively simple immune system seen in lower vertebrates such as birds and fish," says Belov.
"Interest in marsupial and monotreme genomes comes from their important positions in vertebrate evolution," says Belov. (Monotremes are egg-laying mammals, represented today by only the platypus and echidna.) "Comparing genes of placental mammals, such as the human and the mouse, is not very efficient because their genes can be so similar it is hard to pinpoint regions that remain unchanged because they serve a particular purpose. In contrast, comparison of distantly related genes, such as the chicken and human, can be difficult, because the sequences are so different."
"Marsupial and monotreme genomes fill this gap. They are easily aligned with placental mammal genomes, yet are different enough to pinpoint regions that have important functions and therefore have been conserved for long periods of time. The monotremes split off from other mammals 210 million years ago. The remaining marsupials split from the main (placental) group about 180 years ago."
Significantly, the authors also found data supporting the idea that there was an ancient relationship between the MHC and another critical component of the immune system, the natural killer complex (NKC), which contains natural killer (NK) cell receptor loci. This "immune supercomplex," which no longer exists in modern genomes, performed the MHC functions in ancestral mammals. "Understanding the immune system of marsupials and monotremes will help us to conserve our native species," Belov says.
The paper is the result of international collaboration between Australian National University (ANU), The Walter and Eliza Hall Institute of Medical Research, the University of New Mexico, Texas A&M, the Southwest Foundation for Biomedical Research and the University of Pittsburg and is published in the highly regarded journal PLoS Biology.
Citation: Belov K, Deakin JE, Papenfuss AT, Baker ML, Melman SD, et al. (2006) Reconstructing an ancestral mammalian immune supercomplex from a marsupial major histocompatibility complex. PLoS Biol 4(3): e46.
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