Thanks to Brilliant for supporting this episode of SciShow. Go to Brilliant.org/SciShow to
check out their Computational Biology course.
{♫Intro♫}
Hot springs and hydrothermal vents might not be the first places you’d look to find ways
to fight a pandemic.
But they’ve given us some of the most important tools we have for identifying, tracking, and
understanding pathogens.
In fact, without them, the entire field of molecular biology would be stuck in the 1960s,
and not in the fun way.
See, that’s when researchers discovered a microbe in Yellowstone that allowed them
to actually replicate DNA at will.
This process—known as Polymerase Chain Reaction, or PCR for short—was really a game changer
for genetics.
And we here at SciShow do not use that phrase lightly.
The pathway to developing PCR began way back in the middle of the twentieth century.
Scientists had just really seen DNA for the first time, but already, they were searching
for ways to read these genetic blueprints. FST01
Problem was, sequencing DNA—and its simpler cousin, RNA—required a lot of genetic material,
because it relied on cutting longer strings into smaller ones with enzymes that sliced
at certain sequences, and then back-calculating what the whole string looked like from those
pieces.
And, simply put, it wasn’t easy to obtain that volume of genetic material—especially
for anything not microbial in nature.
So they knew being able to make copies of DNA would open the door to all kinds of research.
And the potential to do that traces back to 1957—just a few years after the structure
of DNA was first described—when researchers identified the first DNA polymerase.
These enzymes build strands of DNA from nucleotides, the essential building blocks of nucleic acids.
They take a single strand of DNA as a template, and string together a complementary strand.
And all organisms have the blueprints for at least one of these enzymes written into
their genetic code. That’s how they make copies of their genome when their cells divide.
Researchers soon discovered that they could isolate these enzymes from bacteria like E.
coli, which meant, hypothetically, they could use them to replicate any DNA they wanted.
Except, there was a small catch.
Before the polymerase can start copying DNA, the tightly wound, paired strands of DNA found
in organisms like us have to be separated into single strands.
That way, short sequences of single-stranded DNA called primers can bind to the open strand
and tell the polymerase where to start and stop copying.
In nature, this unwinding requires yet another enzyme, plus a several other proteins—too
complicated to recreate in a tube.
Luckily, DNA strands can be separated another way.
Above 90°C, the bonds holding the strands together break apart.
So you can heat up DNA to get single strands, then cool things down a bit to let the primers
bind and so DNA polymerase can make its copies.
After each heating and cooling cycle, you essentially double the amount of DNA.
Today, each of these cycles takes about five minutes, so within a few hours, you can go
from a very small number of copies to millions of copies of a given DNA sequence.
But in the ‘60s, the whole process took much longer than that.
See, heat also permanently inactivates the DNA polymerases from E. coli.
So, in early DNA replication efforts, fresh polymerase had to be added each time a copy
of DNA was made—making the process very slow and very expensive.
That’s where extreme microbes come into play.
P05 In 1966, scientists discovered a microbe living
in the 70-plus degree waters of hot springs in Yellowstone National Park.
They named it Thermus aquaticus, after its ability to thrive in the hot spring’s high
temperatures.
And in 1976, researchers isolated one of its DNA polymerases.
They called it Taq polymerase—or, just Taq, for short.
And, like the microbe itself, it could withstand the high temperatures needed for separating
DNA strands.
So you could throw it in with your sample, some primers, and nucleic acids, and then
let a machine heat and cool everything over and over again to produce millions of copies
of DNA.
And that, in a nutshell, is Polymerase Chain Reaction.
Ever since researchers developed these methods in the mid eighties, PCR has allowed scientists
to turn teeny amounts of DNA into much larger ones in a matter of hours.
For geneticists, it was like going from carbon-copy paper to a Xerox machine!
It meant they could figure out whose cells are on the end of a hair at a crime scene.
Or, spot the genes of a virus hiding in someone’s blood.
In short, Taq polymerase revolutionized genetics. And it’s still widely used for PCR today.
But newer enzymes are coming into play, too.
See, Taq sometimes makes mistakes. It grabs the wrong nucleotide and attaches it instead.
This is a problem for applications that need a high level of accuracy—like, if you’re
trying to detect the small mutations that can happen to a virus over time.
Doing that can help experts understand how the pathogen is moving about and changing.
Luckily, researchers discovered Pyrococcus
abyssi—a deep sea microbe that lives in even more extreme conditions.
Its enzymes are more resilient than Taq, but more importantly, they also proofread themselves
while making copies—which is why they’re forty to fifty times more accurate.
They’re now among the several specialized polymerases available to geneticists.
And researchers keep going back to extreme environments because their microbes have all
sorts of unique and useful molecular tricks up their sleeves.
So who knows what else we’ll discover by studying these remarkably resourceful organisms.
PCR didn’t just provide new tools for studying viral outbreaks, of course. Suddenly, scientists
could use genetic information to study all sorts of evolutionary and biological questions.
And you can learn all about that with the Computational Biology course from Brilliant.
Brilliant offers dozens of interactive and engaging STEM courses to take your science,
math, and engineering skills to the next level. And with their Computational Biology course,
you can really dig deep into all the amazing things researchers can learn from sequencing
genetic molecules.
Plus, if you’re one of the first two hundred people to sign up for an annual Premium subscription
at Brilliant.org/SciShow, you’ll get twenty percent off! So if you’re interested,
check it out!
{♫Outro♫}