Prokaryotic Adaptive Immunity
In 1987, Japanese molecular biologist Yoshizumi Ishino noticed an oddity in an E. coli gene he was studying. It had short, repeating sequences of nucleotides, with 2 repeaters having unique sequences (now known as spacers) between them.
It took 2 decades for geneticists to figure out what Ishino’s discovery meant. In 2007, researchers showed that that the genic repeaters and spacers served as part of an adaptive immune system, herein called pais (an acronym for prokaryotic adaptive immune system). (The prokaryotic adaptive immune system, encapsulated as pais, has hitherto been awkwardly known as CRISPR/Cas. The gene editing tool called CRISPR/Cas9 is covered at the end of the chapter.) Microbes evolved innumerable such immune systems which work in slightly various ways.
Overall, prokaryotes appear to have evolved a nucleic acid-based “immunity” system. ~ French American geneticist Rodolphe Barrangou et al in 2007
Prokaryotes have ever been plagued by viruses. To remember the experience (if they live through it), they preserve the remnants of encountered viral villains within a DNA profile (a spacer bookended by 2 repeater caps).
Prokaryotes can store information in specific loci in their DNA to remember encounters with invaders (such as bacteriophages – viruses that infect bacteria). ~ Israeli microbiologists Rea Globus & Udi Qimron
Spacers are read by specific enzymes that then cut out any exogenous matching DNA they find, which left untouched would spell an infection.
Pais is powerful, but not all microbes have them. 90% of archaea have a pais, but only 35% of bacteria do.
Pais is useful when microbes encounter enough variety of viruses to make adaptive memory worthwhile. But if there is too much viral variety, or viruses are rapidly adapting, pais won’t help, because a microbe might never encounter the same virus again.
All known microbes that live in super-hot environments have pais, as the environment is a fairly stable ecosystem, with a middling viral diversity, which means pais might help.
No immunity comes without a cost. ~ Israeli microbial geneticist Rotem Sorek
Pais has downsides. Microbes may accidentally make spacers from bits of their own DNA, creating an auto-destruct sequence. This rarely happens, as there are built-in preventative mechanisms against it.
(Incoming viral DNA is linear, facilitating its recognition as foreign. A microbe’s genophore is protected because of its circular form. But should a sequence break off and become linear for too long, such as during a stalled replication process, there is a risk of the DNA being taken as alien and encapsulated as a spacer.)
Viruses can fight back against pais, morphing into unrecognizable forms. Alternately, they may develop counter weaponry.
The bacterium Pseudomonas aeruginosa, which resides in soil and water, and can cause dangerous infections in macrobes, has a vigorous pais. Some viruses are not in the least fazed by it. That’s because those viruses have wily proteins that gum up P. aeruginosa’s pais.
Viral anti-pais measures are so common that it leaves geneticists wondering how many pais systems are truly active. There is a tremendous diversity in how vigorously microbes employ their pais as an immune response.
Some E. coli carry a pais that they leave switched off. Why bother? Microbes decide what cellular baggage they keep. They could pitch their pais if it made no difference – thus it must, even if seemingly inactive.
There are many mysteries about pais. For one, spacers should reflect the individual story of the viruses a microbe has encountered. Some do, but most seem generic, and the contents of many remain a conundrum.
Is it the case that there is a huge, unknown amount of viral dark matter in the world? ~ Eugene Koonin
One bacteriophage (a virus that infects bacteria) carries its own pais with it, using it to fight the bacterial defense system that the virus encounters upon infection. The viral pais smartly chops up the segment of bacterial DNA that normally inhibits phage infection.
Beyond the problematic fight against viruses, it’s not always smart for a prokaryote to keep out foreign DNA, which may contain the makings of a useful trait.
Microbes that lack pais are not helpless. Far from it. As much as 10% of the genome of a pais-poor prokaryote may be dedicated to other hawkish defense systems.
Plus, a prokaryote may acquire a pais as conditions warrant. Prokaryotes are prodigious acquirers of environmentally available gene packages, through horizontal gene transfer (HGT). As a form of community altruism, bacteria commonly produce and exude helpful HGT packages for others, as well as picking up on such actionable intel when seeking a solution to their own problems.
Pais may serve as more than just an immune system. Spacers sometimes act to silence genetic expression. By selectively silencing genes, a bacterium may stop making molecules on its surface that are readily detected by a macrobe that the bacterium is intent on infecting. Without a pais in place, the bacterium would blow its cover and be killed.
This is a fairly versatile system that can be used for different things. ~ Russian geneticist Konstantin Severinov
