ENCODE, the $185-million successor to the Human Genome Project, promises to reveal new details about our DNA. But controversy persists as geneticists remain at odds over one little f-word?"function"
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Twelve years after the completion of the Human Genome Project, its successor made a big splash with one big number: Around 80 percent of the human genome is "functional," the researchers leading the Encyclopedia of DNA Elements (ENCODE) project said. Their claim drew immediate criticism from biologists, many of whom said it is evolutionarily impossible for so much of the genome to truly function for human health.
Seven months later, the controversy continues. Several journals and countless blogs have published opinion pieces about it. Current Biology published its second essay about it April 8. And in late February the journal Genome Biology and Evolution published an unusually harsh takedown that got some attention for zingers comparing ENCODE to Apple Maps, which had a troubled launch with the iPhone 5. How could the meaning of one word?function?be so divisive?
Funded by the National Institutes of Health?s National Human Genome Research Institute, ENCODE was designed to tackle the data generated by the NIH?s Human Genome Project, which determined the sequence of chemical bases?adenine, cytosine, thymine and guanine, the A, C, T and G sequences?that make up human DNA. Some groupings of bases spell out a code to make specific proteins, which do much of the work in cells, but scientists do not know what the lion?s share of base sequences do.
The 98 percent
So ENCODE tested nearly every part of the genome, particularly the 98 percent that is not involved in encoding proteins, looking for clues to what roles they play in the body. This next step was important because scientists were sure that some portions of that 98 percent served as regulators, telling protein-makers when, where and how much to produce. Such a job is critical for normal cellular behavior, yet scientists understood only some specific examples. They did not know if there were more regulators than they had already found or, if others existed, how they worked. Such regulatory regions may help explain the basis of many diseases that seem to be genetically inherited but escape straightforward correlations to particular protein-coding genes.
In September 2012 ENCODE's leaders formally ended the project's main phase of research. They published dozens of peer-reviewed papers, including the lead paper in Nature that said 80 percent of the genome is functional. At the same time they published a database that annotated most of the nonprotein-coding genome with notes on its chemistry. The notes essentially said things such as: "This part binds a protein"; "This part is often tagged with methyl groups"; and "This part is usually tucked away, wound around a protein called a histone." (Scientific American is part of Nature Publishing Group.)
Much of the backlash isn't in response to the database of functional parts that ENCODE created. "The ENCODE project gave the scientific community a huge amount of useful data that is being used around the world," says Chris Ponting, a genomics researcher at the University of Oxford who disagrees with some of the conclusions about functional DNA that came from ENCODE. Instead, the major criticism is that the project's lead scientists overstepped in their conclusions, especially in publicizing the idea that much of the human genome was potentially necessary to human life. Such determinations aren't supported by the science ENCODE did, critics say, and offer the public an inaccurate idea of how genetics and evolution work.
Source: http://rss.sciam.com/click.phdo?i=15c19b38451ed203b6f6c2678c3a6d3e
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