Genome Research is publishing three papers related to the genome of the gray short-tailed opossum, Monodelphis domestica, a small, nocturnal marsupial found in South America. The papers will appear online, concomitant with the publication of the opossum genome sequence in the journal Nature.
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.
Contact:
Katherine Belov, Ph.D.
University of Sydney, Australia
Reference:
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 Res.
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."
Contact:
Andrew J. Gentles, Ph.D.
Stanford University, Stanford, CA, USA
Reference:
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 Res.
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.
Contact:
Leo Goodstadt, D.Phil.
University of Oxford, UK
Reference:
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 Res.
doi:10.1101/gr.6093907
ABOUT GENOME RESEARCH:
Genome Research (genome/) is an international, monthly, peer-reviewed journal published by Cold Spring Harbor Laboratory Press. Launched in 1995, it is one of the five most highly cited primary research journals in genetics and genomics.
ABOUT COLD SPRING HARBOR LABORATORY PRESS:
Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media located on Long Island, New York. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit cshlpress/.
Contact: Maria Smit
Cold Spring Harbor Laboratory
суббота, 2 июля 2011 г.
пятница, 1 июля 2011 г.
Potential New "Twist" In Breast Cancer Detection
Working with mice, scientists at Johns Hopkins publishing in the December issue of Neoplasia have shown that a protein made by a gene called "Twist" may be the proverbial red flag that can accurately distinguish stem cells that drive aggressive, metastatic breast cancer from other breast cancer cells.
Building on recent work suggesting that it is a relatively rare subgroup of stem cells in breast tumors that drives breast cancer, scientists have surmised that this subgroup of cells must have some very distinctive qualities and characteristics.
In experiments designed to identify those special qualities, the Hopkins team focused on the gene "Twist" (or TWIST1) named for its winding shape because of its known role as the producer of a so-called transcription factor, or protein that switches on or off other genes. Twist is an oncogene, one of many genes we are born with that have the potential to turn normal cells into malignant ones.
"Our experiments show that Twist is a driving force among a lot of other players in causing some forms of breast cancer," says Venu Raman, Ph.D., associate professor of radiology and oncology, Johns Hopkins University School of Medicine. "The protein it makes is one of a growing collection of markers that, when present, flag a tumor cell as a breast cancer stem cell."
Previous stem cell research identified a Twist-promoted process known as epithelial-to-mesenchymal transition, or EMT, as an important marker denoting the special subgroup of breast cancer stem cells. EMT essentially gets cells to detach from a primary tumor and metastasize. The new Hopkins research shows that the presence of Twist, along with changes in two other biomarkers CD 24 and CD44 even without EMT, announces the presence of this critical sub-group of stem cells.
"The conventional thinking is that the EMT is crucial for recognizing the breast cancer cell as stem cells, and the potential for metastasis, but our studies show that when Twist shows up in excess or even at all, it can work independently of EMT," says Farhad Vesuna, Ph.D., an instructor of radiology in the Johns Hopkins University School of Medicine. "EMT is not mandatory for identifying a breast cancer stem cell."
Working with human breast cancer cells transplanted into mice, all of which had the oncogene Twist, the scientists tagged cell surface markers CD24 and CD44 with fluorescent chemicals. Following isolation of the subpopulation containing high CD44 and low CD24 by flow cytometry, they counted 20 of these putative breast cancer stem cells. They then injected these cells into the breast tissue of 12 mice. All developed cancerous tumors.
"Normally, it takes approximately a million cells to grow a xenograft, or transplanted tumor," Vesuna says. "And here we're talking just 20 cells. There is something about these cells something different compared to the whole bulk of the tumor cell that makes them potent. That's the acid test if you can take a very small number of purified "stem cells" and grow a cancerous tumor, this means you have a pure population."
Previously, the team showed that 65 percent of aggressive breast cancers have more Twist compared to lower-grade breast cancers, and that Twist-expressing cells are more resistant to radiation.
Twist is what scientists refer to as an oncogene, one that if expressed when and where it's not supposed to be expressed, causes oncogenesis or cancer because the molecules and pathways that once regulated it and kept it in check are gone.
This finding that Twist is integral to the breast cancer stem cell phenotype has fundamental implications for early detection, treatment and prevention, Raman says. Some cancer treatments may kill ordinary tumor cells while sparing the rare cancer stem cell population, sabotaging treatment efforts. More effective cancer therapies likely require drugs that kill this important stem cell population.
This study was supported by the Maryland Stem Cell Research Foundation.
In addition to Vesuna and Raman, authors of the paper include Ala Lisok and Brian Kimble, also of Johns Hopkins.
Source: Johns Hopkins Medicine
Building on recent work suggesting that it is a relatively rare subgroup of stem cells in breast tumors that drives breast cancer, scientists have surmised that this subgroup of cells must have some very distinctive qualities and characteristics.
In experiments designed to identify those special qualities, the Hopkins team focused on the gene "Twist" (or TWIST1) named for its winding shape because of its known role as the producer of a so-called transcription factor, or protein that switches on or off other genes. Twist is an oncogene, one of many genes we are born with that have the potential to turn normal cells into malignant ones.
"Our experiments show that Twist is a driving force among a lot of other players in causing some forms of breast cancer," says Venu Raman, Ph.D., associate professor of radiology and oncology, Johns Hopkins University School of Medicine. "The protein it makes is one of a growing collection of markers that, when present, flag a tumor cell as a breast cancer stem cell."
Previous stem cell research identified a Twist-promoted process known as epithelial-to-mesenchymal transition, or EMT, as an important marker denoting the special subgroup of breast cancer stem cells. EMT essentially gets cells to detach from a primary tumor and metastasize. The new Hopkins research shows that the presence of Twist, along with changes in two other biomarkers CD 24 and CD44 even without EMT, announces the presence of this critical sub-group of stem cells.
"The conventional thinking is that the EMT is crucial for recognizing the breast cancer cell as stem cells, and the potential for metastasis, but our studies show that when Twist shows up in excess or even at all, it can work independently of EMT," says Farhad Vesuna, Ph.D., an instructor of radiology in the Johns Hopkins University School of Medicine. "EMT is not mandatory for identifying a breast cancer stem cell."
Working with human breast cancer cells transplanted into mice, all of which had the oncogene Twist, the scientists tagged cell surface markers CD24 and CD44 with fluorescent chemicals. Following isolation of the subpopulation containing high CD44 and low CD24 by flow cytometry, they counted 20 of these putative breast cancer stem cells. They then injected these cells into the breast tissue of 12 mice. All developed cancerous tumors.
"Normally, it takes approximately a million cells to grow a xenograft, or transplanted tumor," Vesuna says. "And here we're talking just 20 cells. There is something about these cells something different compared to the whole bulk of the tumor cell that makes them potent. That's the acid test if you can take a very small number of purified "stem cells" and grow a cancerous tumor, this means you have a pure population."
Previously, the team showed that 65 percent of aggressive breast cancers have more Twist compared to lower-grade breast cancers, and that Twist-expressing cells are more resistant to radiation.
Twist is what scientists refer to as an oncogene, one that if expressed when and where it's not supposed to be expressed, causes oncogenesis or cancer because the molecules and pathways that once regulated it and kept it in check are gone.
This finding that Twist is integral to the breast cancer stem cell phenotype has fundamental implications for early detection, treatment and prevention, Raman says. Some cancer treatments may kill ordinary tumor cells while sparing the rare cancer stem cell population, sabotaging treatment efforts. More effective cancer therapies likely require drugs that kill this important stem cell population.
This study was supported by the Maryland Stem Cell Research Foundation.
In addition to Vesuna and Raman, authors of the paper include Ala Lisok and Brian Kimble, also of Johns Hopkins.
Source: Johns Hopkins Medicine
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