Genome complexity: idle egg self-protection (Introduction)

by David Turell , Friday, May 17, 2024, 20:00 (16 days ago) @ David Turell

Waiting to be fertilized, should not change:

https://www.quantamagazine.org/how-idle-egg-cells-defend-their-dna-from-damage-20240513/

"Out of all the cells in the body, oocytes are the most patient. The immature egg cells form inside a female’s body when she’s still a fetus in her mother’s womb, and then they wait in a quiescent state for years, if not decades. Cocooned inside ovaries, they pause, neither dividing nor replicating their DNA, so that one day they may pass along pristinely preserved genetic information to the next generation.

"Yet sitting quietly for year upon year without degrading is immensely challenging for cells. Dormancy may reduce the wear and tear on oocytes, but it also reduces their ability to repair the inevitable damage they sustain at the molecular level. Recently, in a study published in Cell, researchers discovered how mouse oocytes keep DNA safe from damaging proteins. The cells construct special compartments within themselves to temporarily sequester the proteins. Then, heeding a molecular signal, the storage units disperse all at once, practically vanishing along with their dangerous cargo. Thus cleaned, the oocyte is left to mature safely.

***

"Oocytes are long-lived, an uncommon trait among cells. A female human baby is typically born with 1 million to 2 million of them. Early in life, the cells are tiny and generally don’t do much — researchers often call them “idle.” But over time they get much bigger: During the first decade of life, human oocytes grow 64-fold — a “massive expansion” that demands a lot from the energy-producing cellular organelles called mitochondria, said Elvan Böke, a cell biologist at the Center for Genomic Regulation in Barcelona, Spain. The number of mitochondria in oocytes balloons from just a few thousand to hundreds of thousands.

"Having lots of mitochondria is normally risky for cells because their chemical activity generates toxic byproducts known as free radicals. But when Böke peered inside dormant human and frog oocytes, they weren’t overloaded with free radicals at all. As she reported in a Nature paper published in 2022, the oocytes’ mitochondria were doing something surprising: They were skipping the step in their energy-generating process that produces these dangerous molecules. This meant that they produced less energy overall; Böke speculated that they direct all the energy they do produce for growth. No other cell had been observed to do this.

***

"Because oocytes expand so massively and produce proteins so intensively during their growth period, Böke expected to see high protein activity in the two major pathways responsible for clearing aggregates. Instead, she saw less activity in immature oocytes than in mature egg cells.

“'It doesn’t make much sense,” she said. “Why would you put your degradative activity down if you’re going to grow and make lots of things?”

"It was because the oocytes weren’t degrading the damaging proteins — they were storing them to destroy later.

"When Böke and her team infused oocytes with a dye that illuminates protein aggregates, she saw the proteins clustered in large compartments. Probing further, she used electron microscopy to reveal these distinct storage units as super-organelles, which she named ELVAs, or endolysosomal vesicular assemblies. These pouchlike objects are composed of lysosomes — the cell’s waste-disposal organelles — and other protein-degrading machinery.

"In young oocytes, they are situated throughout the cytoplasm. Later, as oocytes mature, ELVAs fuse together, relocate and ramp up their degradative machinery. By the time an oocyte is fully mature, harmful protein aggregates are undetectable, and the ELVAs vanish, revealing a clean cytoplasm.

***

"For example, researchers have found that some long-lived stem cells also have ELVA-like components, which capture and store aggregates until the cells are ready to divide. Neurons, too, can develop triage centers, called aggresomes, for organizing misfolded proteins. However, neurons destroy their cellular detritus throughout their life spans, while oocytes store them and then wipe them out all at once. Böke speculated that the oocytes’ method is more energy-efficient: Since their mitochondria produce less energy overall, they need all of it for necessary growth to reach reproductive maturity."

Comment: we all see the concept here, protect myself until I am needed later. These cells show purposeful activity to fuel the concept. Chance mutations cannot do this. Only purposeful design fits.