We hear so much about “CRISPR/Cas9 gene-editing” and the (independent, nearly-simultaneous) co-discoverers (Emanuelle Charpentier and Jennifer Doudna) have won dozens of prizes and recognitions, and they highly likely to win the Nobel Prize soon. On the other hand, some of us ponder things and think more deeply. WHY does CRISPR-Cas exist? How many types are there, and how common is it? I recall having conversations with Stanley N. Cohen (Stanford, early 1970s) “Why do restriction enzymes exist –– in the first place”…?? The attached article delves into the mystery of CRISPR-Cas in semi-layman terms.
The biological advantages of something like CRISPR–Cas are clear. Prokaryotes — bacteria and less-well-known single-celled organisms called archaea, many of which live in extreme environments (heat or cold) — face a constant onslaught of genetic invaders. Viruses outnumber prokaryotes by ten-to-one and are said to kill half of the world’s bacteria every two days…!! Prokaryotes also swap scraps of DNA, called plasmids, which can be parasitic — draining resources from their host and forcing it to self-destruct –– if it tries to expel its molecular hitch-hiker. It seems as if nowhere is safe: from soil to sea to the most inhospitable places on the planet, genetic invaders are present.
Prokaryotes have evolved a variety of weapons to cope with these threats. Restriction enzymes, for example, are proteins that cut DNA at or near a specific sequence. But these defenses are more obvious: 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 manner similar to how human antibodies provide long-term immunity after an infection. “When we first heard about this hypothesis, we thought that would be way too sophisticated for simple prokaryotes,” says microbiologist John van der Oost.
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 (which led to Barbara McClintock, being laughed at for decades, before winning the Nobel Prize). Evolutionary biologist Eugene Koonin and colleagues have found 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.
Researchers have officially recognized today that there exist six different types of CRISPR systems, with 19 subtypes. “And we really only know how a fraction of them actually work,” says Luciano Marraffini (a microbiologist at the Rockefeller University, NY).
Nature 19 Jan 2o17; 541: 280–282