
Dads Pass on More Than Genetics in Their Sperm - pagutierrezn
https://www.smithsonianmag.com/science-nature/dads-pass-more-genetics-their-sperm-180969760/?no-ist
======
stochastic_monk
I remember researchers at the Institute for Systems Biology in Seattle were
showing results in 2011 on traits inherited epigenetically from their fathers
in locations in the genome where histones were still present. (That is, not
more tightly packaged by protamines, which discard a lot of epigenetic
information.)

The point is that Lamarckian inheritance is stronger than we’ve imagined in
our DNA-centric perspective. Of course, inheritance through small RNAs is new
and exciting, but they aren’t the first mechanism for paternal inheritance
outside of DNA sequence.

I’m glad the press is starting to hear, but this isn’t news to anyone in the
field.

------
acqq
I don't see what is "passed on" "more than genetics" when reading the actual
studies:

[https://www.cell.com/developmental-
cell/fulltext/S1534-5807(...](https://www.cell.com/developmental-
cell/fulltext/S1534-5807\(18\)30540-9)

[https://www.cell.com/developmental-
cell/fulltext/S1534-5807(...](https://www.cell.com/developmental-
cell/fulltext/S1534-5807\(18\)30541-0)

Skimming through them, I only understand that the sperms go through different
phases before the fertilization and that the scientist observe some details of
that now. That the whole process is quite complex was know since a while.

Maybe somebody who understands more can explain here?

~~~
matheusmoreira
DNA is transcribed into messenger RNA (mRNA) inside the nucleus of the cell.
mRNA is a sequence of codons, which consist of 3 base pairs each. It is
transported from the nucleus to the cytoplasm where it may undergo translation
into a protein by way of a ribosome. Most codons represent a specific amino
acid, but they may also serve as stop signals.

The ribosome reads the codons off of the mRNA and translates that information
into a sequence of amino acids. In order to know which amino acid to use for
each codon, it uses another kind of RNA, the transfer RNA (tRNA). Each tRNA
contains an anticodon and a covalently linked amino acid. This anticodon is
the complement of the codon that codes for that specific amino acid, and it is
used to recognize the codon and match it to the correct amino acid. Once the
ribosome finds a matching tRNA, it takes its amino acid and adds it to the
protein.

You can see a picture of this process here:

[https://upload.wikimedia.org/wikipedia/commons/0/0f/Peptide_...](https://upload.wikimedia.org/wikipedia/commons/0/0f/Peptide_syn.png)

Why did I explain all this? Because in the first article, the following is
said:

> we confirm and extend prior observations that sperm undergo a dramatic
> switch in the RNA payload from piRNAs to tRNA fragments (tRFs) upon exiting
> the testis and entering the epididymis.

So, as sperm passes through the epididymis, it loses these piRNAs and gains
tRNA fragments. What are these tRNA fragments? They seem¹ to be incorrectly
synthesized tRNA. The tRNAs don't just appear out of nowhere, they're
synthesized in the nucleus, just like mRNA. Before they're ready to be used
for translation, they must undergo various processes such as aminoacylation.
It seems faulty (incorrectly folded?) pre-tRNA molecules are identified and
cut up into these tRNA fragments.

The authors of the article have found that this process occurs frequently in
the epididymis and that the tRNA fragments are exported to the spermatozoa
through vesicles:

> We found that tRNA cleavage occurs robustly in the epididymis and that small
> vesicles secreted by the epididymal epithelium, known as epididymosomes,
> carry a very similar population of small RNAs to that gained by sperm during
> epididymal transit

The epididymis sends tRNA fragments to sperm cells. So what? That's where the
second article comes in: the authors compared the development of embryos
fertilized by both pre-epididymis and post-epididymis sperm. They found that
the pre-epididymis embryos expressed too many regulatory factors during
development and were not able to successfully develop.

> We find that caput-derived embryos significantly overexpress ∼50 genes
> primarily encoding regulatory factors (RNA binding proteins and chromatin-
> associated factors)

If they overexpressed regulatory factors and failed to develop, it can be
inferred that they underexpressed the actual genes and proteins required for
development. This apparently causes what they describe as "pleiotropic defects
in implantation and post-implantation development".

Meanwhile, the post-epididymis embryos were able to develop normally. It can
be inferred that these normal embryos did not express as many regulatory
factors, and that the tRNA fragments gained in the epididymis suppressed the
expression of such factors.

It is already known in medicine that embryo-associated risk factors for
abortion will probably lead to abortion within the first couple of weeks. This
seems to be what's happening here: an epigenetic factor intrinsic to the
embryo prevented its development past a certain early point. In this case, the
female will likely not even know she was pregnant. This seems to be a rather
common occurrence. Nevertheless, it's still quite interesting to figure out
exactly why this happens.

Since the sperm of all males must pass through the epididymis, this seems to
be most relevant for the science assisted reproduction and the procedures
involved. It is my understanding that this knowledge can help decide the
precise location in the genitourinary tract from which to surgically extract a
male's sperm. Also, injection of the epididymal small RNAs into the embryos is
apparently sufficient to rescue it from abortion, so this research might form
the basis of a prophylactic procedure.

¹
[https://www.ncbi.nlm.nih.gov/pubmed/21976287](https://www.ncbi.nlm.nih.gov/pubmed/21976287)

~~~
subroutine
What you are calling "epigenetic factors" have been known as regulatory
molecules since the origins of biology.

 _Epigenetics_ refers to the theory that some of a parent organism's
phenotypes arise as a consequence of its environment/experiences and those
traits can be passed on to its offspring without alterations to the gamete's
DNA sequence.

With that in mind, how does any of this relates to epigenetics? Everything
described here fits under the umbrella of 'basic regulatory milieu' required
for sperm maturation, so it can fertilize an egg and commence embryonic
development. The Smithsonian article is trying to spin this as something it's
not...

 _" It turns out that sperm small RNAs undergo post-testes turnover, picking
up intel on the father’s physical health (or lack thereof) after they’re
manufactured, but before they exit the body."_

It seems like they are trying to sell a classical misconception. They might as
well have said: along the way the sperm picks up epigenetic information by
absorbing its fathers tRNA, which pass on a variety of information about the
father's life experiences, like that he was a body-builder, but also an
alcoholic; and so this offspring will likely develop into that sort of person.

~~~
matheusmoreira
> how does any of this relates to epigenetics?

Epigenetics is the study of changes in organisms caused by modification of
gene expression. If these articles are to be believed, then these tRNA
fragments positively influence the expression of regulatory factors. It seems
like an example of epigenetics to me.

> It seems like they are trying to sell a classical misconception.

I don't disagree with this assessment. The study I cited¹ said something about
tRNA fragments being a conserved response to oxidative stress. The news
article apparently takes this and somehow turns it into a "your children will
feel the consequences of your bad dietary habits" argument.

There is some discussion and references about diets and epigenetics in the
scientific text but that's not what the article is about. The articles say (1)
the epididymis sends some RNA to the sperm cells, and (2) that the lack of
this RNA can compromise embryo viability. It's interesting and all, but the
clinical relevance of this information has yet to be determined: I'm not aware
of any evidence that supports the notion that bad lifestyle habits will affect
this sperm maturation process in any way.

¹
[https://www.ncbi.nlm.nih.gov/pubmed/21976287](https://www.ncbi.nlm.nih.gov/pubmed/21976287)

> Accumulation of RNAs of 30–35 nucleotides that correspond to tRNA halves
> were first reported in Tetrahymena thermophila, and subsequently shown to be
> a conserved response to oxidative stress in a wide variety of eukaryotes.²

²
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2553748/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2553748/)

~~~
subroutine
This definition you provide...

 _Epigenetics is the study of changes in organisms caused by modification of
gene expression._

...is not sufficient. The crux of epigenetics is that it involves >heritable<
changes in gene expression.

At least that's what it originally meant. Now I feel like the definition is
transforming into the definition you gave. However the author of the
smithsonian article is confusing the two usages, because in several places the
article alludes to the heritability.

------
annamargot
How does this affect the theory of evolution?

In the 90s in high school, we were taught that _random_ mutations create
diversity among a species and then natural selection chose the winning
mutations. Do they still teach that?

Is behavior and environment generally accepted to be a factor in mutations
nowadays?

The random thing always struck me as inefficient.

Edit for clarity.

~~~
TangoTrotFox
I think there's a related issue here that's always kind of nagged at me.

We have evolved many characteristics which are handy, but which seem unlikely
to have had enough of an impact on survival to have become so ubiquitously
propagated by natural selection alone. For instance the ability to digest milk
as well as white skin are both relatively new adaptations. But the advantages
they offer, for the locations where they evolved, are pretty mild.

Fair skin could have had sexual selection factors in play helping its spread,
but being able to digest the milk of lactating animals? It just doesn't seem
like a mutation that would provide enough benefit to become ubiquitous through
the mechanisms of natural selection alone, yet it did. And both of the above
evolutions are relatively recent, making it all the more difficult to
reconcile things through random mutations filtered by natural/sexual selection
alone.

~~~
torstenvl
I'm confused by your viewpoint. How is a fuller ability to extract
nutritionally-complete food from your environment in winter _not_ an advantage
you'd expect to be selected-for?

People who are malnourished produce poorer sperm. People who are malnourished
are not looked on as good mates who can bear children or provide food for the
family. People who are malnourished die earlier, perhaps starving to death
before reproducing (or reproducing as much).

~~~
TangoTrotFox
Think about your usage of the word word people - as opposed to the singular.
In a purely random natural selection driven system, propagation relies on the
success of a single mutated individual until we get to _very_ large
populations where randomness could more regularly yield similar mutations
among different people. Because of this, in the purely random natural
selection system the magnitude of an effect is extremely important. Let's
imagine we can somehow quantify exactly how likely a specimen is to survive in
a certain area per year, we'll call that value x. Imagine x is some percent
per year. How much would a random specimen suddenly developing lactose
tolerance increase that percent?

In the case of something like Darwin's birds, the percent improvement from
beak changes would be very substantial. That mutation would open up entirely
new, and vast, resources of food available at all times and completely
independent of everything else. In the case of milk, you need a lactating
animal to start with. That already implies you have multiple sources of food
in extremely healthy shape. That little catch there already ensures that this
mutation would not provide a substantial benefit _in a one-off scenario._

By contrast, imagine our mutations are not entirely random. And that our
bodies, somehow, trend towards more desirable mutations over time -- meaning
we don't see just a one-off instance of favorable mutations but them tending
to occur over and over again. In this case your language of "people" would be
entirely appropriate. Over time, even a small survival edge means a lot and,
given enough samples, we'd certainly expect this trait (and any trait for that
matter) to start to 'stick' in any area where its net effect on survival was
basically anything above 0.

~~~
pjscott
I'm not seeing the issue here. As you say, let's talk about this at the
individual level: picture yourself as a prehistoric pastoralist raising
cattle. They eat plants you can't digest, and from them you get milk and meat.
Everybody knows that you can't just drink the milk raw -- the lactose in there
will really do a number on your digestive system -- but _processed_ milk
products like cheese make up a major part of your diet.

... Except that _you_ can digest the lactose. You don't feel sick after
drinking milk, because you have a mutation that breaks the normal mammalian
mechanism for reducing lactase production in adulthood. Sounds nice, right?
But maybe not something that'll bring a huge reproductive advantage to you and
yours; more of a cool party trick to show off to your neighbors.

And then one year there's not nearly enough rain. Famines have always been
pretty common, alas, and here's another one. Now consider this: processing the
milk so lactose-intolerant people can digest it loses about 40% of the
calories. You can drink it straight because of your freaky mutant milk-
drinking powers, and your neighbors can't. You get a lot more food at a time
when people are dying from lack of food. Is this sounding like an evolutionary
advantage? The sort of thing you might pass on to the kids you'll have because
you didn't starve?

The ability to digest lactose as an adult is potentially a _really big deal_
if you happen to live in a culture that already uses processed milk products
as a major source of calories.

~~~
TangoTrotFox
Dairy products would not have made up a substantial portion of a regions diet
until lactose tolerance had emerged. Lactose intolerance extends to all dairy
products, not just milk. And again, you need lactating animals to produce
consistent dairy products. Animals do not naturally lactate unless they're
feeding their young. And animals also do not naturally produce the freakish
amount of milk that we're able to extract now a days from millennia of
artificial selection and, in the US at least, using a lifelong cocktail of all
sorts of different drugs.

To be clear, I do agree with you that in certain uncommon scenarios lactose
tolerance could provide a tangible, though not enormous, advantage. And that's
the problem. A different shaped beak for a bird entails a never-ending
constant, and enormous, advantage. Lactose tolerance is something that's
pretty irrelevant by comparison, yet it would become ubiquitous.

------
chiefalchemist
Interesting. Very similar to some of the female-centric "tricks" mentioned in
this book (review).

[https://www.theatlantic.com/magazine/archive/2018/07/carl-
zi...](https://www.theatlantic.com/magazine/archive/2018/07/carl-zimmer-she-
has-her-mother-s-laugh/561710/)

------
victor106
If anyone is interested in this subject the book “The Gene” by Siddartha
Mukerjee is amazing. One of the best books I have read this year.

~~~
philippoi
Haven't read it but remember coming across some critique of 'The Gene' when it
came out. Could be good to read along with the book to be aware of some of its
contentious areas.

[https://www.spectator.co.uk/2016/05/how-siddhartha-
mukherjee...](https://www.spectator.co.uk/2016/05/how-siddhartha-mukherjee-
gets-the-gene-wrong/)

------
update
> For instance, mice born to fathers that experience stress can inherit the
> behavioral consequences of traumatic memories. Additionally, mouse dads with
> less-than-desirable diets can pass a wonky metabolism onto their kids.

This is likely being studied already, but I wonder what this means in regards
to depression.

------
Torwald
In the capture to the title picture, there seems to be a typo "vas deferens"
instead of "vast difference." Correct me if I am wrong, non native speaker
here!

~~~
zqbit
Look up vas deferens, it's a pun.

~~~
Torwald
Haha it is.
[https://en.wikipedia.org/wiki/Vas_deferens](https://en.wikipedia.org/wiki/Vas_deferens)

To my deferens, it vas vast over my head.

------
finmin
the 2 examples given of epigenetic inheritence are due to malnutrition and
stress - but what about timing ? What if a person was malnurished and/or
stressed in the past but is now happy and eating well - what does the
epigenetic imprinting fade or will his kids suffer due to his past ?

------
a3n
So if an individual who is less fit for survival due to behavior is still able
to reproduce, the traits that reduce that individual's fitness, or their
results, are passed on and could still stop that line due to a descendant
eventually not being able to reproduce due to their apparent unfitness.

~~~
bilbo0s
Not to put too fine a point on it...

but if an individual is able to reproduce, as far as Mother Nature is
concerned, that individual was fit for purpose. She really doesn't care about
the rest.

~~~
a3n
I don't think so. Non-optimal results are always possible at any moment. What
I'm suggesting is that natural selection doesn't merely manifest at the moment
of reproduction (and that any result at that moment is circularly optimal
because it happened), but that in addition, degrees of selection can also
gradually deter traits over a series of descendant reproductive opportunities.

The under-fit grandfather may have reproduced in his moment because there
wasn't anyone better around to displace him, in that moment, but there are
more chances to repress that particular under-fitness in any descendants that
carry it.

~~~
bilbo0s
"...but there are more chances to repress that particular under-fitness in any
descendants that carry it.."

And Mother Nature wouldn't care about that either, even if it were likely to
happen. Which it isn't.

Reproduction has nothing to do with any "fitness" other than the biological
ability to reproduce. Mother Nature really doesn't care whether we think an
organism is "fit", she just wants more kids. In fact, the poor could be
considered "less fit" in a certain view, but they reproduce the most. Because
in the eyes of Mother Nature, they are perfectly "fit". There will never be a
time that Mother Nature deems them "unfit". The unfit will _always_ have the
ability, the inclination, and the opportunity to reproduce. That's just how
she works.

We don't have to like it, but that doesn't make it any less true.

------
KenanSulayman
tl;dr "there's also epigentics"

It has been known for some time already that there's not only genetics (as in
DNA), but also epigenetics (i.e. markers that can enable or disable sections
of the DNA; they can change over time based on environmental factors). I'm not
exactly sure what's the news in this article?

~~~
delinka
Is that "known to the scientific community" or "known anecdotally"?

The news here seems to be that there's now scientific confirmation of what was
known anecdotally.

~~~
Xikkub
Epigenetics has been known about and studied for probably two decades at this
point; as SimbaOnSteroids said, the real news here is the previously unknown
role of the epididymis in changing the epigenetic cargo of sperm.

------
pyrophane
> "Seminal research reveals..."

The author couldn't resist.

~~~
subpixel
I presumed someone would beat me to this.

~~~
mrkgnao
Most sperm, too, are beaten to it by others

~~~
senectus1
Third stroke of the "pen is" quick enough..

