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Dads Pass on More Than Genetics in Their Sperm
- acqq 8y agoI don't see what is "passed on" "more than genetics" when reading the actual studies: 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 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?
- subroutine 8y agoThis article is egregious in its sensationalization of epigenetics, which is nothing new, but particularly odd in this case given this research had nothing to do with epigenetics whatsoever.
- matheusmoreira 8y agoDNA 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_syn.png 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. ¹ https://www.ncbi.nlm.nih.gov/pubmed/21976287 https://www.ncbi.nlm.nih.gov/pubmed/21976287
- euyyn 8y agoThanks for the informative and clear explanation!
- deleted 8y ago[deleted]
- subroutine 8y agoWhat 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 8y ago> 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/
- pyrophane 8y ago> "Seminal research reveals..." The author couldn't resist.
- subpixel 8y agoI presumed someone would beat me to this.
- jkaplowitz 8y agoNor could the photo caption writer resist an even better pun: "For sperm, there’s a vas deferens between start and finish [...]" Both are good though.
- anonu 8y agoYes! Great use of words.
- jjdredd 8y agoAlso: "In the past several years, mounting evidence has shown that sperm can take ..."
- KenanSulayman 8y agotl;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 8y agoIs 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 8y agoEpigenetics 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.
- SimbaOnSteroids 8y agoThe new part of the article is the previously unnoticed role of the epididymis. It turned out that upon entering the epididymis sperm shed a bunch of small RNAs(which play a major role in epigenetic expression) and then reaquire small RNA's that reflect more closely the father's environment, later along in the duct.
- annamargot 8y agoHow 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.
- delinka 8y ago"The random thing" is indeed efficient. That's why it takes millions of years to evolve from single-celled organism to what you see on the planet today.
- annamargot 8y agoYeah, that’s what my teachers said too. “Millions of years. End of conversation. Put your hand down, son.” 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.
- delinka 8y agoWhile I suppose "informed best guess" might be possible, I don't see how this 'intelligence' makes it into the process. Liver more stressed in this particular organism? Tweak the DNA in the reproductive organs. I don't think we even have a theory that could explain how that should work. Maybe we'll get there one day. 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.
- dahlueblojen 8y agoTo be fair most grade school teachers just have a bachelor's in their subject (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.
- victor106 8y agoIf 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 8y agoHaven'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-gets-the-gene-wrong/ https://www.spectator.co.uk/2016/05/how-siddhartha-mukherjee...
- chiefalchemist 8y agoInteresting. Very similar to some of the female-centric "tricks" mentioned in this book (review). https://www.theatlantic.com/magazine/archive/2018/07/carl-zimmer-she-has-her-mother-s-laugh/561710/ https://www.theatlantic.com/magazine/archive/2018/07/carl-zi...
- a3n 8y agoSo 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.
- isoprophlex 8y agoIn a similar vein, what will happen to our species given the availability of cesarean sectiond?
- bilbo0s 8y agoNot 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 8y agoI 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 8y ago"...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.
- stochastic_monk 8y agoI 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.
- update 8y ago> 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.
- finmin 8y agothe 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 ?
- Torwald 8y agoIn 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!