Barbarian
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When it comes to genome size, a rare Japanese flower, called Paris japonica, is the current heavyweight champ, with 50 times more DNA than humans. At the other end of the scale, there’s now a new lightweight record-holder growing in petri dishes in California. This week in
Science, researchers led by genome sequencing pioneer Craig Venter report engineering a bacterium to have the smallest genome—and the fewest genes—of any freely living organism, smaller than the flower’s by a factor of 282,000. Known as Syn 3.0, the new organism has a genome whittled down to the bare essentials needed to survive and reproduce, just 473 genes. “It’s a tour de force,” says George Church, a synthetic biologist at Harvard University.
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In their current work, Venter, along with project leader Clyde Hutchison at JCVI, set out to determine the minimal set of genes needed for life by stripping nonessential genes from Syn 1.0. They initially formed two teams, each with the same task: using all available genomic knowledge to design a bacterial chromosome with the hypothetical minimum genome. Both proposals were then synthesized and transplanted into M. capricolum to see whether either would produce a viable organism.
“The big news is we failed,” Venter says. “I was surprised.” Neither chromosome produced a living microbe. It’s clear, Venter says, that “our current knowledge of bio logy is not sufficient to sit down and design a living organism and build it.”
Venter and his colleagues had better success with trial and error. They divided Syn 1.0’s genome, with its 901 genes, into eight sections. To the beginning and end of each section they added identical DNA tags that made the pieces easy to reassemble. That allowed them to treat the sections as independent modules, removing each one in turn, deleting chunks of DNA, then reassembling the full genome and reinserting it into M. capricolum to see whether it produced a living cell. If the altered genome wasn’t viable, they knew they had cut out an essential gene that had to be restored. The researchers also assessed the necessity of numerous genes in the microbe by inserting foreign genetic material, called transposons, to disrupt their function.
All this enabled them to systematically whittle away genes that either had nonessential functions or duplicated the function of another gene. In the end, Venter says, his team built, designed, and tested “multiple hundreds” of constructs before settling on Syn 3.0, with a genome about half the size of Syn 1.0’s. (Syn 2.0 was an intermediate stage in this process, the first microbe with a genome smaller than that of M. genitalium, which with 525 genes has the fewest of any free-living natural organism.)
http://www.sciencemag.org/news/2016/03/synthetic-microbe-lives-less-500-genes
The remaining task is to find out what those unknown 150 or so genes do. Once that's clear, the development of a completely synthetic organism is possible.
Brave new world that has such organisms in it.
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In their current work, Venter, along with project leader Clyde Hutchison at JCVI, set out to determine the minimal set of genes needed for life by stripping nonessential genes from Syn 1.0. They initially formed two teams, each with the same task: using all available genomic knowledge to design a bacterial chromosome with the hypothetical minimum genome. Both proposals were then synthesized and transplanted into M. capricolum to see whether either would produce a viable organism.
“The big news is we failed,” Venter says. “I was surprised.” Neither chromosome produced a living microbe. It’s clear, Venter says, that “our current knowledge of bio logy is not sufficient to sit down and design a living organism and build it.”
Venter and his colleagues had better success with trial and error. They divided Syn 1.0’s genome, with its 901 genes, into eight sections. To the beginning and end of each section they added identical DNA tags that made the pieces easy to reassemble. That allowed them to treat the sections as independent modules, removing each one in turn, deleting chunks of DNA, then reassembling the full genome and reinserting it into M. capricolum to see whether it produced a living cell. If the altered genome wasn’t viable, they knew they had cut out an essential gene that had to be restored. The researchers also assessed the necessity of numerous genes in the microbe by inserting foreign genetic material, called transposons, to disrupt their function.
All this enabled them to systematically whittle away genes that either had nonessential functions or duplicated the function of another gene. In the end, Venter says, his team built, designed, and tested “multiple hundreds” of constructs before settling on Syn 3.0, with a genome about half the size of Syn 1.0’s. (Syn 2.0 was an intermediate stage in this process, the first microbe with a genome smaller than that of M. genitalium, which with 525 genes has the fewest of any free-living natural organism.)
http://www.sciencemag.org/news/2016/03/synthetic-microbe-lives-less-500-genes
The remaining task is to find out what those unknown 150 or so genes do. Once that's clear, the development of a completely synthetic organism is possible.
Brave new world that has such organisms in it.