
Mosaicism: The genome varies from cell to cell - bookofjoe
https://www.nytimes.com/2018/05/21/science/mosaicism-dna-genome-cancer.html
======
lisper
I sometimes give lectures on evolution and I usually open with this classic
puzzle (due to Dawkins): most ants (and other social insects) are sterile. How
is this possible? Why would evolution select for genes that produce sterile
individuals? (You might want to see if you can figure this out before
continuing.)

The answer is that ants are not organisms, they are _organs_. The ant _colony_
is the organism. It just happens to be made of parts that are not physically
connected to each other.

Well, it turns out that humans are much like ants in this regard. A single
human individual cannot reproduce. Even a single fertile couple cannot
successfully reproduce in the wild (if you doubt this, watch a few episodes of
Naked and Afraid). The minimum viable reproductive unit for homo sapiens is a
tribe or a village.

This sort of organizational grouping is found at _all_ of the levels of
abstraction in life. Even your DNA is not really a unified whole, it's a bunch
of genes that have glommed together in a cooperative effort to reproduce
themselves, but it's not an organized or homogeneous effort. That's why you
have freeloaders ("junk DNA") and defectors (cancer genes) who put their own
interests above those of the group. What happens at the cellular and molecular
level is really not so different from what happens in human societies. The
presence of brains changes the dynamic, but not in any fundamental way. At the
end of the day, it's all just self-replicating information looking for an
ecological niche and a reproductive edge. The idea that human individuals are
somehow special in this process is mostly a prejudice brought on by our
particular point of view, namely, the fact that our thoughts reside in brains
that are strongly bound to bodies. The ability to see beyond onesself can be
both powerful and humbling.

~~~
hnaccy
>Even a single fertile couple cannot successfully reproduce in the wild (if
you doubt this, watch a few episodes of Naked and Afraid). The minimum viable
reproductive unit for homo sapiens is a tribe or a village.

Do you have evidence for this that's not a reality TV show?

Edit: I have found the Lykov family who had two children in isolation; they
did already have two children who would have been 13 and 6 at the time of the
third child's birth in isolation.
[https://en.wikipedia.org/wiki/Lykov_family](https://en.wikipedia.org/wiki/Lykov_family)

~~~
lisper
> Do you have evidence for this that's not a reality TV show?

Yes. Let's start with the fact that there are no recorded instances of an
isolated human couple successfully reproducing in the wild ever. Merely having
a baby doesn't count. To be a viable evolutionary strategy you have to raise
that baby to maturity and then that baby has to reproduce themselves.

In fact, this is not unique to humans. It's true of _all_ simians. In fact,
it's true for the vast majority of mammals. The only exceptions I can think of
are some species of cats: leopards, cheetahs, tigers, mountain lions.

We can also reason from first principles: you need a minimum viable population
in order to maintain genetic diversity. So even if it were possible for
isolated human couples to reproduce, you'd need more than one instance of
this, and these families would somehow have to _find_ each other in order to
procure mates. How are they going to do that?

~~~
Retric
Don't mistake modern density for a requirement. It's hard to find instances of
anyone living alone for long periods, but that likely changes as you go back
and there where fewer people and those people where more able to survive in
the wild.

I remember going into back country with some friends as a teen, miles into
'the middle of nowhere'. Second day camping I see someone run by in yoga pants
pushing a stroller as it turns out we where about 300 feet from a ski trail
and people would run down the mountain in the summer for fun.

~~~
lisper
Don't mistake a small loose end in a complex argument condensed to fit in an
HN comment for proof that the argument is wrong.

~~~
Retric
Well the holes in your arguments are deeper than that. A viable strategy need
not be the only or even the optimal strategy.

If couple has kids and those kids find someone in a local tribe then both
tribes and lone families would have worked. In effect you are trying to
redefine his argument not just in terms of recorded history but also both
couples not an individual one.

~~~
lisper
> If couple has kids and those kids find someone in a local tribe then both
> tribes and lone families would have worked.

You're attacking a straw man. Of course a couple can reproduce _if_ they are
in proximity to a tribe. But that still requires a tribe. It is a couple _in
isolation_ that is not viable.

~~~
Retric
The couple are irrelevant at that point. People can travel ~10,000 miles a
year on foot. The fact their kids leave in no way impacts them being in
isolation. Heck, someone can know where other people are and still be
isolated.

QED they can reproduce in isolation.

~~~
lisper
I rarely see people on HN miss the point quite this badly. Reddit, yes, but
not here.

The point is: for your scenario to play out, a tribe has to _exist_ (and it
has to be close enough for the couple's offspring to find it, but that's a
detail). No tribe, no viable reproduction. Hence, the tribe is the minimum
viable unit, _even if_ it also occasionally supports an isolated couple
somewhere in the vicinity.

~~~
barrkel
Your argument is only true in the trivial sense that sexually reproducing
organisms are only viable in larger numbers than a single pair; but that's a
distinction that doesn't demarcate anything interesting. Humans are like ants,
you say, but your argument also leads to the same conclusion about tigers,
bears and other solitary animals in that they need more than a breeding pair
to be viable. It descends into tautology.

Yes, humans are somewhat like ants in that they are usually social. Humans are
adaptable enough to survive in pairs, though lack of specialization means they
won't necessarily live the most comfortable life, so it would be an unusual
choice. But there's nothing elective about ants' socialism. So in the end I
don't think your argument works.

~~~
lisper
> your argument also leads to the same conclusion about tigers, bears and
> other solitary animals in that they need more than a breeding pair to be
> viable

No. Those species have specialized adaptations that allow them to live in
isolation, which humans lack. And it's not just humans. All simians lack these
adaptations. Indeed, the vast majority (perhaps all -- I can't think of a
single counterexample) of non-carnivore mammals lack them.

------
jessriedel
I found that spending a bit of time visualizing the scale and complexity of
cells is helpful for not finding this sort of messiness surprising. A similar
thing that used to surprising me was the idea that some viruses, like herpes
simplex, hide out inside cells for years and years.

A cartoon of the HIV life cycle:
[https://blogs.scientificamerican.com/observations/watch-
the-...](https://blogs.scientificamerican.com/observations/watch-the-life-
cycle-of-hiv-in-colorful-new-detail/)

The complexity insides eukaryotic cells is startling, and compared to
individual molecules they are massive. (Prokaryotic cells are 0.1 - 5 microns,
while eukaryotic ones are 10-100 microns. That means eukaryotic cells are
larger in volume by 2-9 orders of magnitude! It also lowers the impressiveness
of comparisons between the number of gut bacteria cells and human cells.) If
you think of each cell as a person, then the body is an army of 30 trillion
soldiers each with his own copy of instructions to follow (which he copied
from someone else) and many possible ways to get hurt or die. It's not so
surprising that some fractions of the soldiers will have very small errors in
their copy of the instructions, which they will pass on as copies to other
soldiers, or that individuals could get a tape worm and still fight.

~~~
eternalban
Scale factors in biological systems are collosal. It amuses me when I hear
e.g. Alan Kay talk about objects as biological cells. (Conceptually, sure.)

~~~
Balgair
Yes, the thermodynamics alone are vastly different between an Elephant and a
mouse, let alone between an Elephant and a bacterium. We are somewhat
fortunate that life can exist across such vast scales, as it really gives us a
lot of things to study and think about.

~~~
eternalban
I meant the scale range when considering the constituent components of any
given biological organism:

Let's say we take the hardware basis -- cpu, instruction sets, registers,
buses, etc. -- as the 'organic chemistry' analogue -- the substrate. Just the
basic cell, which is a profoundly amazing machine, would require layer upon
layer of software. By the time we reach the level of an 'organ' or 'system'
along the biological model, it would be a monster.

We humans, for example, have apparently (per my search engine) somewhere
between 10^13 to 10^14 cells. That's 4 to 5 orders of magnitude larger than
the total number of computers on this planet.

------
karimf
I'm amazed at how much we still don't know about our human body. Engineering
in other areas, like computer sciences, is much easier because we understand
the fundamental concept behind it. But in bioengineering or pharmacy, a lot of
them are trial and error, and serendipity, because I think we simply don't
really understand how the cell actually work in details yet. [0]

[0] One discussion about this:
[https://news.ycombinator.com/item?id=16079735](https://news.ycombinator.com/item?id=16079735)

~~~
adrianN
It would be easier if cells had an intelligent designer and weren't just soups
of chemicals that interact in millions of ways.

~~~
gowld
Looking at my job's code base, I'm not sure that would help.

~~~
shagie
I am reminded of an old Usenet post... proof of the existence of the System
Administrator.
[https://everything2.com/title/Existence+of+the+System+Admini...](https://everything2.com/title/Existence+of+the+System+Administrator)
is the copy I can find on google.

From the argument from design:

> One looks at a simple computer, and sees evidence of intelligent design.

> One looks at a Sun Sparc 20 and... um... well... Okay, One looks at a DEC
> Alpha and sees evidence of intelligent design.

And from the counter argument:

> If you think the network implies intelligent design, you haven't seen our
> network.

------
blacksmith_tb
The article doesn't touch on X-chromosome Inactivation[1] which makes all
female animals mosaic. Though in the specific case in the article SCN5A isn't
on the X[2].

1:
[https://en.wikipedia.org/wiki/X-inactivation](https://en.wikipedia.org/wiki/X-inactivation)

2:
[https://ghr.nlm.nih.gov/gene/SCN5A#location](https://ghr.nlm.nih.gov/gene/SCN5A#location)

~~~
tamcap
X-chromosome inactivation is a type of an epigenetic change. It is one of many
that happen throughout the body - I would say there are very few cells in our
bodies that have the same epigenetic markup. We've known about this for a
while.

The article discusses genetic post-meiotic changes that propagate
differentially through the body. We knew it happened for a while now too, but
it was always presented as a curiosity or an anomaly. We are now learning that
it is much more common than we anticipated. Like presented in the article, it
might actually explain some clinical phenotypes as well.

~~~
hinkley
Don’t organs, limbs, spots and stripes form in a fetus due to epigenetics?

~~~
rubatuga
You're not wrong, it's a mixture of epigenetic changes, and local environment
changes. As a cell differentiates, it definitely changes its epigenome. These
changes are also mediated by cell-cell interactions, and other morphogenic
proteins, for example, the SHH gene:
[https://en.wikipedia.org/wiki/Sonic_hedgehog](https://en.wikipedia.org/wiki/Sonic_hedgehog)

------
Symmetry
I'm surprised the article didn't mention immune system mosaicism, where
populations of immune cells have mutations that allow them to look for
different proteins. And I've heard a neuroscientist speculate that the reason
there is so much brain mosaicism is to allow different neurons to express
different surface proteins and allow them to recognize and avoid attaching to
themselves.

~~~
rubatuga
I'm not so sure if you mean mosaicism for the immune cells. Do you mean VDJ
and VJ recombination in TCR and BCR chains?

------
stevenwoo
Does this effect or render incomplete the results people get from services
like 23 And Me? The doctor treating the baby had to do multiple DNA tests to
verify the mosaicness, and was only able to determine the 5%/12% _bad_ cells
in the heart right/left after it was removed.

~~~
rubatuga
It definitely changes a few gene results. An interesting and related topic to
mosaicism is chimerism, where in the case of Lydia Fairchild, she was told her
daughter wasn't hers because of different DNA populations in the mother's
body.

[https://en.wikipedia.org/wiki/Lydia_Fairchild](https://en.wikipedia.org/wiki/Lydia_Fairchild)

------
chiefalchemist
Is this related to epigenetics? If so, how?

I mean, I would think that it's not so much external factors influencing your
genes directly, per se. But certain genes being called into play and others
not.

Or is - likely? - a combo of both? That is internal genetic variance, as well
as the ability to be influences by external factors. It would seem, the latter
would be the ideal, the most flexible / advantageous.

------
stochastic_monk
I'm looking forward to everyone understanding this. In the field, we've known
that somatic mosaicism is important for decades. (And there was the bombshell
somatic retrotransposition within the brain discovery back in 2011 [1]) that
showed that more active rearrangements were happening.) But public
understanding of scientific issues takes time. I think they're starting to
know that sexual orientation and transgender identity are driven by
biochemical processes, and that took decades as well.

[1]
[https://www.nature.com/articles/nature10531](https://www.nature.com/articles/nature10531)

~~~
milankovic
So, crime is driven by biochemical processes as well?

~~~
javier2
Maybe a predisposition to moral deviance is biochemical?

~~~
milankovic
Downvoted for asking a simple question?

Is that what HN has come to? Really?

I'm really sorry my friend.

They (downvoters) fail to realize that they are shooting the messengers,
nothing more. But smart people understand. They know and will never cease to
keeping them honest..

~~~
abiox
> Downvoted for asking a simple question

this seems a bit reductive.

sometimes people asking leading questions that are a bit... let's say tired,
aren't all that interesting. if there is a point to be made, they should just
make it.

"smart people" (as you say) sometimes prefer forthright discussion.

------
bookofjoe
Wait, what? When I posted this article an hour ago I did so with the exact
headline used in the New York Times: "Every Cell in Your Body Has the Same
DNA. Except It Doesn’t." Now it's got a new title (here, not in the Times).
What gives? Who did this?

~~~
jMyles
From the HN guidelines:

> use the original title, unless it is misleading or linkbait.

The original title was arguably both. :-)

~~~
bookofjoe
You know, at first I said WTF? — but you are right. Frankly, I've noticed the
Times is increasingly resorting to headlines that wouldn't be out of place in
USA Today or the Daily Mail. :-)

~~~
sctb
You've got that right.

------
GuiA
Can someone explain the grammar behind the title? It feels wrong, but the fact
that it presumably passed NYT's copyediting leads me to believe it is correct.

What's the "it" referring to in the title?

The body? But the body itself has no DNA to properly speak of.

A single cell? That is not what the article is saying.

Trying to use the same construct for a different sentence:

 _" Every person in this room should have worn a suit. Except he didn't"_ -> a
single person in the room didn't wear a suit, and I am probably looking at him
while saying this.

 _" Every person in this room should have worn a suit. Except they didn't"_ ->
there are several people in the room who didn't wear a suit, this feels closer
to the meaning of the piece's title?

~~~
raverbashing
"It is raining" "It isn't"

It's the same thing.

