Dads Pass on More Than Genetics in Their Sperm
smithsonianmag.com
smithsonianmag.com
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.
https://www.cell.com/developmental-cell/fulltext/S1534-5807(...
https://www.cell.com/developmental-cell/fulltext/S1534-5807(...
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?
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_...
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.
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.
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
> 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
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.
"Also, injection of the epididymal small RNAs into the embryos is apparently sufficient to rescue it from abortion"
From my point of view at least, this is still "genetics": tomato, tomatho, RNA, DNA. RNA has just one "building block" (and there are many of the same in each) different than DNA: no thymine but uracil. Because something is in RNA and not in DNA it's not by magic "not genetic." It's all the part of the same complex mechanism of carrying the genetic information using some complex molecules, all based on the same principle. It's just that the mechanism is more complex than some obviously unsubstantiated simplification.
Whoever ever tried to see how it actually looks like knows how complex that is:
https://youtu.be/DfB8vQokr0Q?t=193
The "life" building blocks are mind-bogglingly complex to whoever expects something where 3D forms and small differences and immense parallelization don't work at the same time in astounding number of instances (e.g. a single human body has some 37 trillion of cells.. all made from a single one!).
Moreover without the different "gene expression" mechanisms doing their job there would never be any multi-cellular life, there would be neither me nor you: every multi cellular being starts from only one instance of the "program" yet the cells develop with different functions in every multi cellular body (and all these cells still contain the same program, until some mutation happens in some of them). So there is a fundamental mechanism that allows for the same "program" to behave differently a the different moments and with the different environment, even when the "environment" means the "different neighbor cells." Not to mention that what starts the new being is never just the lone DNA (which would simply not survive alone) but the fertilized cell containing all the mechanisms around that DNA (including RNA and a lot of other stuff... the whole "factories," "supply roads," "transport vehicles", "power centrals" etc, to use the equivalent words we are familiar with. A lot of these mechanisms are provided by the mother, but why should we be surprised that some are from the father too, carried with the sperm cell? We see them there. These mechanisms are all the part of the process, it's nothing "more" than it is, and it was there since the life as we know it exists.
And the (from my understanding still misleading) title about which I asked was that claim that somehow something was "passed on" that is "more than genetics".
In short, it appears to me to be an example of
https://en.wikipedia.org/wiki/No_true_Scotsman
"No true Scotsman fallacy" when somebody redefines some term "by changing the definition in an ad hoc fashion to exclude" what he wants to present as an "counterexample."
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.
It always seemed a little dismissive of the potential of our now very complex organisms to use feedback if only purely random mutations were at play.
Instead of random mutations full stop, how about informed best guess mutations targeted at potentially stressed areas of the body.
But I suspect, as has been demonstrated in labs with bacteria, that it really is random. When their environment begins to show signs of contamination, the bacteria's inner workings don't use an "informed best guess" when mutating for reproduction - the random changes result in bacteria suited for death with exposure to the contamination, and bacteria that are more resistant to the contamination. Guess which ones survive to pass on the trait.
(if you're lucky) (also don't include masters of education, that's about teaching, not the subject matter being taught)
that they aquired a decade or so ago. It's not surprising if what they know is well what they were taught and not what is most current.
First off, if you teach at the middle or high school level, you have to have a masters in the subject you teach. It's called a single subject credential.
Secondly, just like college professors, who continue to learn about new developments in their field, a lot of K-12 teachers, and especially 7-12 teachers, do that too. They also read papers and also attend conferences to learn the latest developments in their field.
2nd case is probably fair, though I think a lot of people, myself included, have has experiences with teachers that definitely didn't pay attention in those seminars if they attended. (And in my case that's just with 1.5 years of middle school)
That’s not true, some states don’t require a Masters in any subject, let alone in one relevant to what they’re teaching.
https://study.com/articles/High_School_Teacher_Requirements_...
https://teach.com/become/teaching-credential/state-requireme...
He's written a fascinating paper exploring what other algorithms besides random search could perform the computational task required and are also biologically plausible: https://dash.harvard.edu/bitstream/handle/1/2643031/valiant_...
Some new stuff include: epigenetics, the role of 'junk dna', small RNA etc.
Overall I am very enthusiastic about epigenetics
Mostly interested in basic scientific knowledge (say high school level) that has been updated.
... or those trying to have an meaningful conversation with someone from another generation. I honestly have no idea what my parents were taught in school. I’ve often wonder how much of this plays into the narratives that get exploited in politics.
In the 19th and 20th century, scientists debated how evolution and speciation could take place. The Darwinian side said it was purely chance-based mutations combined against selective pressures--natural selection. The Lamarckist school suspected this was statistically unlikely and posited that organisms had the ability to pass down acquired traits. They debated fiercely, and the Darwinists declared victory based on Occam's razor because no mechanism was ever discovered whereby acquired traits could be transmitted.
In the 2000s, the U.S. saw some political controversies in which creationists tried to have their anti-evolutionary religious views included in classroom science. The debates around that issue helped solidify a new dichotomy of science vs. religion when it came to the discussion of evolution. During the same era, the study of epigenetics was becoming popular. Owing perhaps due to the aforementioned political discourse of the era, the public at large has allowed epigenetics to be subsumed into the existing theory of evolution as if it is no change at all. From a different perspective (a la the Lamarckists of centuries past,) it represents the possibility of a diametrically opposed paradigm shift.
In these comments there are already comments dismissing epigenetics matter-of-factly as just a part of natural selection. In the purview of scientific history, it's the opposite of natural selection.
To answer your question, the reality is this is very different than what you were taught in the 90s, except that we've rewritten history for science to save face and pretend we knew this all along, and to forget that this sort of thing was explicitly rejected by the Darwinian victors 100 years ago.
Also, the heritability and stickiness of epigenetics is still not well known. It cannot be the main driver of evolution over long intervals (i.e. hundreds of thousands of years) because it is limited in the changes it can make: methylation, for example, can only affect the expression of genes, but it cannot alter them, nor can it introduce new genes.
Yeah, don't answer questions if you don't know the answers.
It is not that different. There still is DNA and epigenetics has not proven Darwin wrong or Lamarck right.
To have a big pool for recombinations, inbreeding is to be avoided and populations must be big enough.
IIRC that's not completely true. In mammal females, there is competition at the chromosome level to determine which member of each pair will end up in the first polar body (which is discarded) and which one ends up in the secondary oocyte (which then splits up to become the ovum and the secondary polar body).
So, ignoring mutations, the next generation gets a never before seen chromosomes that are a puzzle of the chromosomes of the mother and another never before seen chromosomes that are a puzzle of the chromosomes of father.
I still can't find how common is the crossover, but in one link I got about 70 crossovers during the formation of the egg (with a lot of variations), that is approximately 3 crossovers per chromosome. I guess the crossover rate for the sperm is similar.
There is an exception with the X and Y chromosomes in males, that can't crossover, so the Y chromosome is inherited without crossovers, and it's much easier to track the male ancestor line in the Y chromosome. See https://en.wikipedia.org/wiki/Y-chromosomal_Adam
Like a virus that doesn’t need a penetration mechanism because it’s literally Trojan horsed into the egg.
A virus without a penetrator is basically like a cassette tape of DNA.
Derpy egg plays random cassette tape, baby’s DNA is... well the books are cooked as they say. Traits, emerge.
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.
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).
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.
... 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.
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.
That is flatly incorrect. Whoever convinced you this is true has a fundamental misunderstanding of natural selection.
Any time environmental pressures change such that a particular phenotypical expression leads to more reproductive success, that is natural selection. A mutation is utterly unnecessary.
I have a lot of reservations. And I often times find myself rather disgusted by the attitude and approach of many people in the scientific worldview.
That being said, I do believe there are some interesting numbers out there about how much more efficient dairy is than just simply eating your animals. It also produces a relatively large amount of fat, which is is incredibly important (for your brain, and much else) and is one of the more difficult parts of a diet to attain in most ecosystems.
There could possibly also be advantages related to the ease of lactobacillus fermentation.
Nature doesn't really care about efficient, if you want proof of that just look into various places in our body. All over the place you seem completely idiotic design that is merely a result of nature just choosing the lazy, quick and dirty route over the efficient one.
In giraffes this nerve can be 4 meters long.
The likely reason for this layout is that the nerve originally routed to the gills, which were on the height of the heart until the neck extended and the heart moved lower in the body.
https://www.theatlantic.com/magazine/archive/2018/07/carl-zi...
https://www.spectator.co.uk/2016/05/how-siddhartha-mukherjee...
This is likely being studied already, but I wonder what this means in regards to depression.
To my deferens, it vas vast over my head.
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.
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.
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.
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?
The news here seems to be that there's now scientific confirmation of what was known anecdotally.
The author couldn't resist.
"For sperm, there’s a vas deferens between start and finish [...]"
Both are good though.
"In the past several years, mounting evidence has shown that sperm can take ..."