Preventing Misfolding by Preventing Folding | Hacker News Reader

Preventing Misfolding by Preventing Folding

science.org

63 pointssurprisetalk5 comments

Finding a cogent explanation for yet another category of "junk-DNA"/non-coding region is quite encouraging. Yes, things are turning out to be more complicated than we thought, but they are also more comprehensible than we feared, at least once we figure out the right way to look at things.

> There are people who will tell you that a cell is just the way that ribosomes make more ribosomes, and I’m not in a position to say that they’re wrong. It’s for sure that these protein-synthesizing factories are extremely ancient, extremely well-optimized, and they’re constantly at work in every living cell reading off sequences from messenger RNA molecules and extruding the corresponding protein sequences.

I recognize that our bodies are biomechanics in action. I’ve read this multiple times over the years. But there’s something fresh (to me) in the way Dr. Lowe describes them as (paraphrasing): “ancient technology, in use, today”.

It’s both a comfort and a curse as I think about it from this perspective.

These are called highly conserved sequences [1] meaning that they reappear all over the evolutionary tree and studying how they mutate is how we got a lot of our most fundamental knowledge about evolution, especially the first few billion years.

The peptidyl transferase center that helps form the main catalytic binding site [2] on ribosomes is so conserved that it’s immediate ancestors could predate protein synthesis altogether (it’s made of RNA instead of amino acids). Some like the Hilstone H4 protein mutate so slowly that there’s a two amino acid difference out of 102 across complex multicellular organisms, so it’s thought to be critical for gene expression. Then there are ultraconserved non-coding elements which haven’t changed all even though they seem to be unexpressed introns.

There’s lots more like that, many of them used to align sequences so we can actually compare genetics across species.

[1] https://en.wikipedia.org/wiki/Conserved_sequence

[2] This is what uses the 3’UTR to know when to terminate the protein sequence.

Derek Lowe has a very distinct voice.

My joints may be inflexible, but at least I can't be misfolded!

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