CRISPR #2 - Billion-Year War

In 1986, Yoshizumi Ishino found something weird in the DNA of the E.coli bacteria, writes Walter Isaacson in The Code Breaker:

“He found five segments of DNA that were identical to each other. These repeated sequences… were sprinkled between normal looking sequences of DNA, what he called “spacers”.”

He didn’t dig deeper, but did publish his observation.

 

By 1992, such repeated sequences and spacer segments were being found in more and more bacteria. Weirdly, these repeated sequences were palindromes.

(Palindromes are words and even sentences that read the same from front to back, and back to front. Examples include Malayalam and “Able was I ere I saw Elba”. DNA palindromes means the DNA letters – A, T, G and C - read the same in both directions).

 

This raised the question - The genetic code of bacteria is very small (obviously). Why would they “waste” it in duplicating stuff? Unlikely, right? Did that then mean that it must serve some purpose after all?

 

Francisco Mojica dug deeper, trying to understand the biological usefulness of such repeated sequences of DNA in bacteria. But first, he gave it a name: CRISPR - clustered regularly interspaced short palindromic repeats. (Few can remember the expansion, but the acronym was/is easy to pronounce).

 

Ruud Jansen realized that CRISPRs (the repeated sequences) always had genes that had instructions for making enzymes. This was curious – there are so many different types of proteins, so why were there only enzyme coding genes next to CRISPR’s? He decided to call them CRISPR-associated, or Cas enzymes.

 

Remember those spacers? They were the sequences of regularly looking DNA between CRISPR snippets. Mojica found something intriguing about the spacers – they matched DNA sequences of viruses that attacked the bacteria…

 

It all made sense – the CRISPR’s were like markers or flags. Between these markers lay a snippet of DNA code corresponding to a virus that attacked the bacteria. In other words, the details of the attacker virus was stored in the bacteria’s DNA. It was like an immune system mechanism to “remember”.

 

Even better, if a new virus attacked the bacteria, and the bacteria survived the attack, it would add a snippet of the new attacker’s DNA into its own DNA. In the CRISPR format. This was a learn-and-add-as-you-go mechanism.

“Sort of like cutting and pasting a mug shot of dangerous viruses.”

 

The icing on the cake? Since DNA is transmitted to one’s offspring, the bacteria could now transfer all this “knowledge” to its descendants.

 

CRISPR, it turned out, was an ancient defense mechanism invented by bacteria in their billion-year war with viruses that attacked them.

 

Interesting indeed. And, as happens so often, writes Isaacson:

“Discoveries can have unexpected applications.”