https://www.nature.com/articles/d41586-019-03061-x
Levy, A. (2019). How evolution builds genes from scratch. Nature, 574(7778), 314–316. https://doi.org/10.1038/d41586-019-03061-x
How evolution builds genes from scratch
Scientists long assumed that new genes appear when evolution tinkers with old ones. It turns out that natural selection is much more creative.
QT:{{”
Kat – Do you think that there are other pseudogenes lurking the genome that have this kind of roles that are actually not drunk and not dead, and could be very active and important?
Howard – Yes, indeed. So, I think over the last several years, the other investigators have found have resembled from the ENCODE project that many pseudogenes are actually being transcribed, that they’re made. They’re evidence of their activation and that work was led by a Professor Mark Gerstein from Yale. More recently, other people have realised that pseudogenes because they’re copies of normal genes, they have many of the same regulatory sequences embedded in them. And so, when the pseudogenes are made, because of these regulatory sequences, compete for different cellular factors.
“}}
https://www.thenakedscientists.com/articles/interviews/turning-pseudogenes
https://www.science.org/doi/10.1126/science.adg7492
Cheng, J., Novati, G., Pan, J., Bycroft, C., Žemgulytė, A., Applebaum, T., Pritzel, A., Wong, L. H., Zielinski, M., Sargeant, T., Schneider, R. G., W, A., Senior, Jumper, J., Hassabis, D., Kohli, P., & Avsec, Ž. (2023). Accurate proteome-wide missense variant effect prediction with AlphaMissense. Science, 381(6664).
https://doi.org/10.1126/science.adg7492
Levy, A. (2020, January 6). A world without pain. The New Yorker. https://www.newyorker.com/magazine/2020/01/13/a-world-without-pain
QT:{{”
“When I met Jo for the first time, I was just struck by her,” Cox, an affable forty-year-old with a scruffy beard, told me, one afternoon in his lab at U.C.L. …This imperviousness to pain is what makes her distinct from everyone else with a FAAH mutation. They, like even the most committed stoners, can still get hurt.
Cameron had the same FAAH mutation that many other people have—but there had to be something else at play. The scientists started their inquiry by isolating DNA from her blood, and then analyzing the protein-coding subset of her genome—the part that’s traditionally considered to be significant. “We didn’t really find anything,” Cox said. “So we decided, O.K., why don’t we look across the whole genome for bits that are deleted or duplicated? And, at the time, this new chip was just available, which enabled us to scan the whole genome and look for deletions”—snippets missing from her genetic code. “It was a lucky strike: we found that there was this deletion. But it was distinct from FAAH. It was away from FAAH, just downstream.”
The scientists noticed that the right edge of the deletion overlapped “a gene that was annotated as a pseudogene,” Cox said, and frowned. “Which is a term I don’t like.” A pseudogene is what’s been thought of as genetic detritus—a copy of a gene that’s just sitting there, not doing anything productive. One biochemist I spoke to likened a pseudogene to a rusted-out car you stumble on in the forest—only, in Cameron’s case, they put a key in the ignition and the car turned on. “To call it a pseudogene is misleading, because this is a gene that is expressed—it makes a product, a sequence in the DNA,” Cox said, with excitement. “It’s a real fascinating class of genes which have been severely overlooked in genetics until very recently.” Cox and his colleagues named this particular pseudogene—“It’s nicer to call it a gene,” he insisted—FAAH OUT. “It was a wordplay, really,” he said sheepishly. “The challenge now is to understand what it’s doing. Jo is the first person in the world that we know of with this.”
Cameron’s case is important in genetics, partly because it may supply evidence that pseudogenes are more significant than they were previously thought to be.
“}}
https://www.pnas.org/doi/10.1073/pnas.2313581121
Kogan, V., Molodtsov, I., Fleyshman, D. I., Leontieva, O. V., Koman, I. E., & Gudkov, A. V. (2024). The reconstruction of evolutionary dynamics of processed pseudogenes indicates deep silencing of “retrobiome” in naked mole rat. Proceedings of the National Academy of Sciences, 121(45). https://doi.org/10.1073/pnas.2313581121
Sequence Variants in TAAR5 & Other Loci Affect Human Odor Perception & Naming https://www.cell.com/current-biology/fulltext/S0960-9822(20)31343-9 A variant in TAAR5 affects the perception of fish odor. Interesting to consider in relation to pseudogenization of the olfactory receptors
While about half of human odorant receptors are thought to be pseudogenes with loss-of-function, the Decode Genetics folks show that some sequence variants in odorant receptor genes are not
loss-of-function.
QT:{{”
“The oestrogen receptor achieves this by binding substances that contain a chemical structure called an aromatized A ring. Because oestrogens are the only steroid hormones to have such a ring, that criterion was enough to ensure that the receptor bound only oestrogens for many millions of years. Until, that is, the chemical industry started pumping out hundreds of substances containing such aromatized rings, which the oestrogen receptor unwittingly bound. “The endocrine disrupters are taking advantage, unfortunately, of the promiscuity that is the result of the evolutionary history of receptors,” Thornton says.”
“}}
Prehistoric proteins: Raising the dead
http://www.nature.com/news/prehistoric-proteins-raising-the-dead-1.10261
Alternative evolutionary histories in the sequence space of an ancient protein https://www.Nature.com/articles/nature23902 Great viz of different potential but not necessarily realized evolutionary trajectories. Quite relevant for molecular #evolution & #pseudogenes
linkstream2 microblog 