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The opossum genome sequence casts light on evolution, immunity, and disease

  May, 14 2007 23:26
your information resource in human molecular genetics
Genome Research published three papers related to the genome of the gray short-tailed opossum, Monodelphis domestica, a small, nocturnal marsupial found in South America.

1. A fresh start for immune-related genes

Like all marsupials, opossums are born without a functioning immune system; they develop immunological tissues, organs, and the ability to produce antibodies outside the shelter of the mother’s body. The genome sequence of the opossum—the first for any marsupial—provided Dr. Katherine Belov and her colleagues the opportunity to compare immune-related genes in opossums with those in humans.

Belov’s team aligned 1528 human immune-related proteins to the opossum genome, and found that the genetic constituents of the human and opossum “immunomes” were quite similar. “Given the similarities, opossums would make an ideal model organism for developmental immunology studies in mammals, including humans,” says Belov.

Katherine Belov, Ph.D.
University of Sydney, Australia

Belov, K., Sanderson, C.E., Deakin, J.E., Wong, E.S.W., Assange, D., McColl, K.A., Gout, A., de Bono, B., Speed, T.P., Trowsdale, J., and Papenfuss, A.T. 2007. Characterization of the opossum immune genome provides insights into the evolution of the mammalian immune system. Genome Research. doi:10.1101/gr.6121807

2. New functions for ancient DNA

Transposable elements (TEs) are mobile, repetitive DNA sequences that can provide insight into evolutionary processes. “The opossum genome has been bombarded by TEs,” explains Dr. Andrew Gentles, the first author on a paper that describes the first comprehensive survey of TEs in any marsupial. “TEs cover around 52% of the opossum genome, which is higher than any other amniotic lineage studied to date.”

Gentles and his colleagues also discovered ancient TEs that appear to have been recruited for specific biological activities. For example, they identified MER131, a non-protein coding sequence that is highly conserved in the human, chicken, and opossum genomes but absent from zebrafish and frogs. They suggest that MER131 acquired a new function—possibly in regulating gene expression—about 300 million years ago, before the evolutionary divergence of birds and marsupials.

“MER131 is one of many non-coding DNA sequences that are conserved across an amazing variety of species, covering several hundred million years of evolution,” says Gentles. “As more genomes are sequenced, we will find more pieces of these molecular jigsaw puzzles that can help us trace the influence of TEs in the development and function of modern genomes.”

Andrew J. Gentles, Ph.D.
Stanford University, Stanford, CA, USA

Gentles, A.J. Wakefield, M.J., Kohany, O., Gu, Wanjun, Batzer, M.A., Pollock, D.D., and Jurka, J. 2007. Evolutionary dynamics of transposable elements in the short-tailed opossum Monodelphis domestica. Genome Research. doi:10.1101/gr.6070707

3. Colonizing colossal chromosomes

The opossum autosomes (non-sex chromosomes) are unusually large—up to three times longer than the largest human chromosome. When Dr. Leo Goodstadt and his colleagues scrutinized these chromosomes, they discovered that genes situated near the edges of the chromosomes were better at removing mutations that may lead to disease.

“Where a gene lives matters,” says Goodstadt. “Genes that lie in the middle of chromosomes are less likely to be shuffled before being passed on to the next generation. So evolution has been pretty good at getting rid of mutations when they’re near the ends of chromosomes, but rather poor at doing so in their middles.”

In addition, Goodstadt’s group identified 2,733 genes that have duplicated in the opossum lineage since its divergence from humans ~170-190 million years ago. These genes contribute to unique physiological and behavioral characteristics in the opossum, including nocturnal foraging, pheromonal communication, immunity, and adaptation to dietary changes.

Leo Goodstadt, D.Phil.
University of Oxford, UK

Goodstadt, L., Heger, A., Webber, C., and Ponting, C.P. 2007. An analysis of the gene complement of a marsupial, Monodelphis domestica: evolution of lineage-specific genes and giant chromosomes. Genome Research. doi:10.1101/gr.6093907

Source: Genome Research Press Release

Message posted by: Robin Kimmel

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