This episode is brought to you by the Music for Scientists album, now available on all
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For more than a billion years, the only life on Earth were single-celled organisms without much of an internal structure.
We call them prokaryotes, and they include bacteria and archaea.
Then, about two billion years ago, something groundbreaking happened:
Some of these organisms developed an internal
compartment where they started storing their genetic material — the nucleus.
Having a compartment like this may not sound like a big deal,
but this more organized structure paved the way for life to become multicellular,
and for it to diversify into plants, animals,
fungi, and algae — a whole new group we call the eukaryotes.
Now, almost every cell in our bodies has a nucleus that protects our genetic code
and commands the activities that keep us alive.
So, given all that, you’d think we’d have a
solid idea of how the nucleus evolved and why. But we don’t.
Scientists do have several ideas, though.
And exploring them can give us clues as to how complex creatures like us came to be.
The basic textbook explanation of how the nucleus evolved is called invagination.
In this hypothesis, a prokaryote’s outer membrane folded inward to form a cavity.
That’s actually why it’s called invagination — because it’s similar
to the word “vagina,” which essentially means a cavity.
Regardless, over time,
lots of invaginations created little wrinkles and pockets inside the cell.
Then, those infolds pinched themselves off,
forming self-contained bubbles — one of which happened to surround the cell’s genetic material.
And voilà: the nucleus.
This hypothesis offers a simple and elegant model of nucleus formation.
Plus, it explains a few things about why the nucleus looks like it does.
For instance, it explains why the nucleus is surrounded by a double membrane instead
of just a single one — because when the outer membrane folded in on itself, it doubled up.
But despite what textbooks say, there are a few reasons this explanation doesn’t hold water.
The big one is that we can’t explain why it would happen. Like,
what would make a cell just start folding in like this?
It doesn’t make sense that it would happen just to create a pocket to protect genetic material,
because invagination involves lots of folds creating several different structures.
To answer this, some researchers have proposed that the infolds evolved for feeding
and acted like mouths. Then, nucleus formation was just a side effect.
But that’s a pretty important side effect for
something that’s stuck around for billions of generations.
Also, invagination by itself just isn’t great at explaining other features of cells,
like the evolution of some of their organelles, or mini-organs.
One of these is the mitochondria, which are the energy centers of cells.
The classic invagination hypothesis says mitochondria evolved from material
that was already in the cell. But... mitochondria have their own, separate DNA.
Really, it seems like they were once another organism that somehow got inside the cell.
So, eventually, scientists came up with other hypotheses to better
explain the evolution of both the nucleus and mitochondria.
The most famous of these is endosymbiosis. It’s a really
popular idea, and over the years scientists have proposed at least 20 versions of it.
The basic idea of all of them is that at some point in history,
one prokaryote swallowed another one, but didn’t digest it.
Scientists aren’t sure which prokaryotes were involved,
but most of them think an archaeon swallowed a bacterium.
Then, the bacterium just kind of hung around, and the two provided
mutual benefits to each other — like offering protection and sharing energy and nutrients.
In the end, this friendship lasted so long that,
eventually, the bacteria evolved into mitochondria.
And either before or after that, the nucleus formed through invagination.
So, this model is a little more complex, and it does solve some things. But it also has its
own problems. Like, there’s a sort of chicken and egg thing with the mitochondria themselves.
It takes a lot of energy for one organism to swallow
another. And the way organisms typically get lots of energy is from mitochondria.
So how did the archaea get the energy to eat that bacterium in the first
place? It’s a question we can’t answer.
Also, this hypothesis retains a lot of the original problems with pure invagination,
too — like why it would happen.
So in 2014, scientists proposed another hypothesis
about how the nucleus got here that dodges these problems altogether.
It’s called the “inside-out” model. And it takes a pretty different approach.
In this idea, the starting point was an archaeal cell
that had bacteria living on its outer surface.
To feed on these bacteria, the archaeon oozed blobby protrusions from its outer membrane,
which very serious scientists have named blebs.
The blebs trapped the bacteria between them.
Then, the archaeon took some of the bacteria’s energy and used it to grow and swell its blebs,
so that it would have even more surface area to trap and feed on more bacteria.
And eventually, the blebs completely engulfed the bacteria and incorporated them into the cells.
In the end, the bacteria went on to evolve into mitochondria.
The archaeon itself turned into the nucleus.
And the blebs became so large that they evolved into a few things — including
the cell’s outer membrane, but also the outer membrane of the nucleus.
Overall, the inside-out hypothesis has several things going for it.
Like, it explains why nuclei have a double membrane. But also,
it jibes with things archaea actually do.
Because they really do form blebs!
Like, in 2020, researchers described an archaeal cell that has a nucleus-like
cell body with bleb-like protrusions.
And they may use these protrusions to exchange material with organisms living on the cell.
So, there is precedence for this sort of thing.
Also? This cell is an Asgard archaea, which scientists think are the closest
living relatives of the archaea that became the first eukaryotes.
And beyond all that, this hypothesis also explains why and how the nucleus evolved: It
was basically a side effect of an archaeon trying to interact with bacteria living on its surface.
That said... there’s still one piece missing.
If the nucleus were originally a standalone archaeon, it would have had the ability to
take the information from its DNA, and use that information to make proteins.
So theoretically, there should be machinery for protein assembly
inside the nucleus. And there isn’t.
In eukaryotes, DNA is copied into another molecule, called RNA. And then, RNA leaves
the nucleus and goes to make proteins elsewhere in the cell, with the help of another organelle.
So, how did that happen?
Well, some scientists have proposed a fourth hypothesis that’s pretty controversial,
but also pretty fascinating: giant viruses.
Scientists discovered these in 2003. And they’re roughly the size of bacteria,
which is huge compared to normal. Like, many viruses are half that size or less.
These giants enter cells and then build compartments called viral factories,
which the viruses use to replicate themselves.
And there are a couple interesting things about these factories.
First, the process of copying DNA takes place inside them,
while the construction of the proteins happens outside.
Which sounds a lot like what happens inside and outside the nucleus in eukaryotes.
Second, giant viral factories happen to be roughly the size of a nucleus.
So, there are two ways these viruses could have played a
role in the evolution of these key structures.
In one version of the hypothesis, a giant virus infected an archaeon and built a viral factory.
The virus stole genes from the archaeon and stashed them in the factory. And then,
over time, it evolved into the nucleus.
This is great, in that it explains why a nucleus would form as a mechanism of protecting DNA:
The virus needed somewhere safe to set up shop and replicate.
And if it’s true, it means that inside every one of your cells are the remnants
of a giant virus! Which is a little disturbing!
The other version of this hypothesis starts the
same way: A giant virus infected an archaeon and built a viral factory.
But in this scenario, the viral factory surrounded both the virus’s genetic material
and the archaeon’s.
Then, the archaeon learned from the virus how to make a factory-like compartment of its own
to protect its precious genetic material.
Overall, this idea that an ancient virus infected a prokaryote is plausible,
because we do see that happening today.
Like, in 2017, researchers found a virus
that infects bacteria and builds viral factories inside of them.
And in 2020, scientists discovered that another
virus forms viral factories that have double membranes.
The downside is,
neither of the giant virus hypotheses explain how these things could have happened.
For example, there’s no explanation of the evolutionary process that
would have turned a viral factory into a nucleus.
Also, scientists haven’t yet found a giant virus
that builds viral factories inside archaea specifically.
So in the end, despite it being this fundamental thing about us and complex life on Earth… we still
don’t know where the nucleus came from, and the only way to sort it out is to do more research.
Fortunately, scientists are constantly discovering new archaea, bacteria, and giant viruses,
in places as diverse as the bottom of the ocean and inside your mouth.
And the more we find out about these ancient organisms,
the closer we’ll get to understanding how nuclei formed, and how we came to be.
If you enjoy thinking about big questions and mysteries like this,
you might also be interested in the Music for Scientists album.
It was inspired by the beauty of science,
as it pushes the boundaries of our understanding and our view of the
world. And it’s a tribute to those who’ve dedicated themselves to science-driven work.
If you want to check it out, click the link in the description to start streaming.
All the songs are great, but we recommend starting with “The Current.”
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