Immunity; Crispr in bacteria (Introduction)

by David Turell , Thursday, January 19, 2017, 01:10 (2867 days ago) @ David Turell

A mechanisms that bacteria use to fight viruses by destroying their DNA, called CRISPR is used by scientists to slice DNA and edit it in experiments:

http://www.nature.com/news/five-big-mysteries-about-crispr-s-origins-1.21294?WT.ec_id=N...

"Today, much more is known about the clustered, regularly interspaced short palindromic repeats that give CRISPR its name and help the CRISPR–Cas microbial immune system to destroy invading viruses. But although most in biomedicine have come to revere the mechanics of the system — particularly of a version called CRISPR–Cas9 — for the ways in which it can be harnessed to edit genes, Mojica and other microbiologists are still puzzling over some basic questions about the system and how it works. How did it evolve, and how did it shape microbial evolution? Why do some microbes use it, whereas others don't? And might it have other, yet-to-be-appreciated roles in their basic biology?

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"Prokaryotes have evolved a slew of weapons to cope with these threats. Restriction enzymes, for example, are proteins that cut DNA at or near a specific sequence. But these defences are blunt. Each enzyme is programmed to recognize certain sequences, and a microbe is protected only if it has a copy of the right gene. CRISPR–Cas is more dynamic. It adapts to and remembers specific genetic invaders in a similar way to how human antibodies provide long-term immunity after an infection.

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"How did bacteria and archaea come to possess such sophisticated immune systems? That question has yet to be answered, but the leading theory is that the systems are derived from transposons — 'jumping genes' that can hop from one position to another in the genome. Evolutionary biologist Eugene Koonin of the US National Institutes of Health in Bethesda, Maryland, and his colleagues have found1 a class of these mobile genetic elements that encodes the protein Cas1, which is involved in inserting spacers into the genome. These 'casposons', he reasons, could have been the origin of CRISPR–Cas immunity. Researchers are now working to understand how these bits of DNA hop from one place to another — and then to track how that mechanism may have led to the sophistication of CRISPR–Cas.

"Many of the molecular details of how Cas proteins add spacers have been worked out in fine detail2 in recent years. But viral DNA is chemically nearly identical to host DNA. How, in a cell packed with DNA, do the proteins know which DNA to add to the CRISPR–Cas memory?

"The stakes are high: if a bacterium adds a piece of its own DNA, it risks suicide by autoimmune attack, says Virginijus Siksnys, a biochemist at Vilnius University in Lithuania. “These enzymes are a double-edged sword.”

It may be that populations of bacteria and archaea can absorb some error, says Rodolphe Barrangou, a microbiologist at North Carolina State University in Raleigh. A few cellular suicides may not matter if other cells can thrive after a viral attack.

"In fact, when viruses infiltrate a bacterial ecosystem, often only about one bacterium in 10 million will gain a spacer that lets it defend itself. Those odds make it hard to study what drives spacer acquisition, and to learn why a cell succeeded where others failed. “It's difficult to catch that bacterium when it actually is happening,” says Luciano Marraffini, a microbiologist at the Rockefeller University in New York City.

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"Whatever other functions CRISPR–Cas has, it is clear that some microbes use it more than others. More than 90% of archaea have CRISPR-based immunity, whereas only about one-third of sequenced bacteria bother with it, says Koonin. And no non-prokaryotic organisms, even single-celled ones, have been caught troubling with CRISPR–Cas at all"

Comment: This is a highly sophisticated immune mechanism that had to be present in the beginning of life for Archaea, the oldest branch of bacteria, to defend themselves against the attacking viruses that probably were present at the same time. It has a form of memory just as we see in humans, which allows for a rapid response to future infections after an initial encounter. Early life was tolo complex for a chance appearance.