>>So we've learned that your body is not just your human cells. That's pretty cool. But
your human cells are still unquestionably a huge part of you, right? Sort of. Now I
have another question for you. Within that minority of cells, those "human" cells that
make up your body, how much of the DNA within the genome of those cells is human DNA? Okay,
that's a trick question because all of it could be called human DNA, but calling it
human DNA also undervalues where that human DNA came from.
Let's start with the mitochondria, that remarkable energy producer of the human cell. Mitochondria
are an essential part of our cells. They are cellular organelles. They are found in nearly
every eukaryotic cell, so it's not just part of humans. What's weird is that mitochondria
resemble bacteria. They even have their own circular DNA, much like a bacteria. And it
turns out this is not a coincidence. If we were to crank back time to roughly 2 billion
years ago, we would see that the common ancestor of us and all other eukaryotes lacked a mitochondria.
We could watch what happened next. We would see where the mitochondria came from. It's
now very obvious that mitochondria were once free-living prokaryotes, bacteria-like organisms
that developed a symbiotic relationship with the precursor to the eukaryotic cell. Basically,
one cell consumes another, but instead of digesting that cell, such as using it as food,
a symbiotic relationship forms.
We still see this process happening today. It's called endosymbiosis. For one example,
let's talk about Paulinella chromatophora. It's a single-celled ameboid, a tiny blob-like
creature and a type of eukaryote that only recently began a symbiotic relationship with
another cell that can perform photosynthesis. In other words, it's getting energy from the
sun. As a result, Paulinella chromatophora can now get energy by photosynthesis. To provide
more detail on how this works, this ameba's new photosynthetic capability is from a new
cellular organelle that originated from a cyanobacteria, a completely different type
of microorganism. The organelle is so young that it's nearly an intact cyanobacteria.
Some of the cyanobacterium's DNA has transferred into the nuclear genome of the ameboid, but
most of the ancestral cyanobacterium's genome remains completely intact. You might ask,
"Why are the cyanobacterium's genes getting transferred into the nuclear genome at all?"
This process of transfer can be sufficiently explained by probability and evolution from
mutation. As you'll see, it's an important process to understand. Bacteria DNA have higher
mutation rates than nuclear DNA. In essence, a bacteria cell is a less stable environment
than the more complex, compartmentalized eukaryotic cell. When a gene from the bacteria gets duplicated
by chance, it may end up by chance in the nuclear genome. These duplication events are
quite common types of mutation. Also, having two copies of the same gene is often inconsequential.
Epigenetic aspects of the cell can typically handle that. Because mutation continues to
be high in the bacteria-like organelle, there's now a greater chance that the gene that remains
in the bacteria will get a mutational damage or potentially get deleted. If that happens,
there's no harm because a back-up copy of that gene is in the nucleus. Overall, we see
that endosymbionts increasingly have their own DNA held within the nucleus of the eukaryotic
cell, rather than remaining in their own structure.
In humans and most eukaryotes, mitochondria have evolved to have more of their mitochondrial
genes in the cell nucleus. That is, they are mitochondrial genes, but they are no longer
in the mitochondria. Using evolutionary principles, we can find these important mitochondrial
genes. Because mitochondria are major powerhouses for our cells, it's important to find these
genes. These nuclear mitochondrial genes are involved in a wide range of important functions,
and variation at these genes explain a wide range of metabolic diseases. Overall, the
mitochondrial genome is less than a tenth of its original size. If we look at what remains
of the mitochondrial genome, we find the free-living ancestor that they have today. It belongs
to a group of bacteria known as Rickettsiales. Rickettsiales bacteria are very fascinating.
In fact, many of these bacteria survive by endosymbiosis even today. And some members
of this order of bacteria are also famous pathogens, causing diseases such as typhus
and spotted fever. In other words, the major energy producer for our cells, the mitochondria,
has quite a few black sheep in its close family.
So the human cell, like nearly all eukaryotic cells, can be thought of as a composite, built
up from an intimate relationship with prokaryotes. This evolutionary relationship is important
to understand. Consider butyrate metabolism. Butyrate is a very important food for cells
that line the colon of your digestive tract. Without butyrate, these colon cells would
eventually die. Butyrate is made by free-living bacteria in your gut when you digest fiber
that you've eaten. In other words, butyrate is a byproduct of your gut microbiome. You
need it to be healthy. And guess who's involved in taking that butyrate and turning it into
energy that your cell can use? You probably guessed it, the mitochondria. I hope you've
started to see that your relationship with bacteria is extremely complicated and very
deeply rooted evolutionarily. Parts of your cells and your genome are quite literally
built up from these prokaryotic foundations, and your intimate relationship with them remains
until this very day.
Recently we have fundamentally changed our relationship with many of these bacteria.
Chlorinated water, highly sanitized food, antibiotics are a major deviation from the
deep evolutionary relationships that we've had. Also, they appear to have a serious consequence.
One of these consequences has been phrased as the hygiene hypothesis, which in brief
argues that inflammatory diseases, such as allergies and eczema and an extremely long
list of other diseases, may have been exacerbated in recent times because how we've changed
our relationship with microbes. It's a hypothesis that connects many diseases of civilization,
or more precisely, diseases of industrialization. Basically our immune systems are becoming
poorly trained, leading them to overreact, even to otherwise harmless stimulation like
pollen. For certain autoimmune diseases this hypothesis appears to be quite true, and there
are still much research to be done to find out where else it might apply.
This is not to downplay the remarkable contribution antibiotics have made to our health, and you
should certainly listen to your physician's recommendations if they prescribe you antibiotics.
I'm quite happy we have these wonderful medical interventions. Western medicine, or more accurately,
evidence-based medicine will improve as we gain a better understanding of our connections
to microbes. But even in its current form, evidence-based medicine has by far the most
reliable track record at saving lives and improving the quality of life than any other
option we have available to us at this time.