
The ramifications of a new type of gene - nopinsight
https://www.economist.com/news/science-and-technology/21737248-it-can-pass-acquired-characteristics-ramifications-new-type-gene
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klmr
As somebody who’s working on a highly related topic, I’m thrilled to see the
research explained so well here. But unfortunately I am unable to assess the
_quality_ of the findings because the researchers have decided to buck
convention and went to the press before publishing their scientific
manuscript.

And this immediately sets off alarm bells: Unfortunately experience shows that
when researchers skip the “due process” of peer evaluation and go directly to
the press they usually oversell their findings. I hope this isn’t the case
here, and the findings hold up under scrutiny.

My own experience is that working with sperm RNA is a b*tch because of high
stochastic noise. It’s basically impossible to get any clear signal from a
whole-transcriptome assay. I’m therefore quite interested in their
quantification.

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neom
In the hypothetical, and the research is good: if I'm stressed out when I'm in
the act of procreation I'll have less stressed out kids??

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klmr
_Maybe_. It’s really too early to say. Even assuming the mechanism described
here is correct, there’s a difference between mice and humans, and there’s a
difference between merely being stressed and a systemic stress response that
would affect the sperm production (which, by the way, doesn’t occur just
during sex but before).

And, finally, the effect on the offspring is completely unclear. _One_ of the
effects, which was reported here, is that offspring is less stressed (why?
how? we don’t know; that’s a major missing puzzle piece). But systemic stress
has quite a few, and partially drastic, effects — increasing expression of a
particular microRNA is just one of many consequences. It also generally
negatively affects semen quality (e.g. [1]), which doesn’t fare well for
procreation.

And even just that particular microRNA in question, MiR-206, is tentatively
implicated in multiple disease predispositions. You might make your children
slightly less stressed. Or you might make it slightly more (or less) likely
for them to acquire muscular dystrophy or schizophrenia.

[1]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382866/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382866/)

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mygo
>and there’s a difference between merely being stressed and a systemic stress
response that would affect the sperm production (which, by the way, doesn’t
occur just during sex but before).

According to the way the research was described, this mechanism acts outside
of the genetic code, so it isn’t a matter of when sperm is produced. These
particles can latch on to the gamete long after the gamete is produced. For
example they can be present along the lining or interstitial fluids in the
epididymis, where sperm passes through from the testes during reproduction.

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petters
After the replication crisis and "Why Most Published Research Findings Are
False," I am very sceptical of statistical findings like this with a
poorly/not understood mechanism.

But the RNA theory at least sounds possible to layperson.

~~~
klmr
> I am very sceptical of statistical findings like this with a poorly/not
> understood mechanism.

And you’re right to be (in fact, this is exactly the same instinct researchers
get). We’ll have to wait until the actual research article is published before
we can assess the quality of their evidence. But in their defence, they
performed a so-called functional verification by knocking out the suspect gene
(MIR206) in mice and looking for phenotypic changes. It is _relatively_
straightforward to perform this in such a way that you get statistically
robust results. And it’s also straightforward to replicate independently,
which will happen in due course.

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bsmithers
An overblown title -- non-protein-coding genes have been known about for a
long time.

However, the transport of micro RNAs on sperm is a pretty cool mechanism -
hope it is correct!

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derivt
Don't know anything about RNA, but I wonder if some kind of small virus could
be used to test the micro RNA transport hypothesis. Googling "micro RNA
virus", first link is
[https://www.ncbi.nlm.nih.gov/pubmed/21431678](https://www.ncbi.nlm.nih.gov/pubmed/21431678)
. The paper seems promising, since 2004, more than 200 microRNAs (miRNAs) have
been discovered in double-stranded DNA viruses, mainly herpesviruses and
polyomaviruses.This chapter aims to summarize our current knowledge of viral
miRNAs, their targets and function, and the challenges lying ahead to decipher
their role in viral biology.

Using microRNA virus to test the sperm transport mechanism seems to be a good
idea. Glooging for "microRNA virus sperm transport" suggest the link:
Intercellular Transport of MicroRNAs
([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580056/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580056/)),
This review brings into focus what is currently known and outstanding in a
novel field of study with applicability to cardiovascular disease.

So, perhaps sperm transport of microRNA could be tested using some RNAvirus to
produce cardiovascular desease.

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klmr
So you’re suggesting injecting viral miRNA into the epididymis of parental
mice and checking for symptoms of viral infection in the offspring? This won’t
work because (a) the miRNA isn’t the whole virus, it probably won’t have a
clearly discernible phenotype; and (b) the mechanism suggested here relies on
specific vesicles. Export of small RNAs into vesicles isn’t an automatic
process, it requires active targeting of the RNA inside the cells for export
(RNAs essentially need to carry a “luggage tag” that directs the cell
machinery to envelope it with a membrane and send it out).

Still, your fundamental idea has some merits. A more promising experiment
would forego viral RNA and instead mutate the specific miRNA-206 in mice to
carry a specific signature. Sequencing the resulting embryo in early
development _could_ show whether the mutated miRNA was taken up. I say “could”
because there are fairly big caveat: miRNAs are short-lived (unless they are
actively regenerated) and the concentrations may be too low to pick up a
signal.

~~~
derivt
The experiment you suggest seems promising. As a math teacher, I don't know
about this field. But to suggest experiments that "could" prove or support and
hypothesis is a good way to advance science. Thanks for our suggestions. As a
Ph.D. math teacher I don't know about this field.

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josephpmay
This is potentially pretty-huge, and a surprisingly well-written non-academic
science article

~~~
Angostura
Virtually all Economist science and technology are written to this standard.
It's a good read.

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golergka
> They could equally well be attached to sperm just before sexual intercourse.
> Ms Chan therefore concentrated her attentions on part of the male genital
> tract called the epididymis. This is where sperm mature. Cells lining the
> epididymis constantly discharge small, fluid-filled, membrane-bound bubbles
> called vesicles. When Ms Chan, working with mice, looked in detail at these
> vesicles, she found that they contained lots of micro-RNAs.

So, if you have unprotected sex with a women who recently was or will be
impregnated by another man, you can still pass your microRNA and affect the
child?

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DrAwdeOccarim
No, it is taken up by the sperm and carried within it into the egg when it
fertilizes it.

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wildbunny
Can't read it due to their pay-wall, anyone post the copy?

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callesgg
[https://pastebin.com/gMQWKwFN](https://pastebin.com/gMQWKwFN)

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nwatson
There's no mention of IVF/in-vitro-fertilization techniques and whether male
micro-RNA can survive that process. There apparently are side effects of IVF
and I wonder whether they could be due to degradation of male RNA transport.

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DrAwdeOccarim
If you do ICSI with sperm taken directly from the testis, which is quite
common, then the sperm never travel through the epididymis and therefore are
not loaded with the microRNAs. So yes, you would certainly have removed the
(is life good or shitty) signal that the sperm normally would carry with them.
The Rando lab at UMass does a lot of this kind of research if you want to go
down the rabbit
hole...[https://umassmed.edu/randolab/](https://umassmed.edu/randolab/)

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j7ake
Can anybody find a link to the paper? Not even a preprint?

~~~
klmr
It hasn’t been published yet.

