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Re:DNA Mutations Do Not Occur Randomly – Discovery Transform... by dekhn on Saturday January 29, 2022 @02:15PM (#30129424)
I think there are entire different categories of genes that lead to nonviable offspring, where some genes are "truly essential for all life" (say, coding for a single ribosomal protein), some genes are "not essential in some rare conditions" (genes for surviving extreme desiccation during wet times), and other genes exist in groups that complex relations where a different subsets could be removed (various synthetic pathways, nothing is truly "necessary", but nothing is truly "sufficient"). These differences have to be addressed through different techniques.

I had a wonderful moment during my postdoc where I discovered a large fractions of genes falsely marked as "essential to life" happened to overlapping genes that were essential to life (IE, parts of both got deleted in the experiment). The underlying paper reporting this was never retracfted but later experiments show if you control for this, many genes aren't "essential" but happen to be overlapping ones that are (thus, you can delete the nonoverlapping part of the nonessential gene and the organism is still viable).

And yes, you're 100% right we already knew that mutation rates are varible. IIUC this paper is arguing for some special process that "protects" functionally important regions from mutation, but I haven't read it in detail and I'm too long gone from the field to make reasonable criticisms.

Re:DNA Mutations Do Not Occur Randomly – Discovery Transform... by gus_massa on Saturday January 29, 2022 @06:34PM (#30131756)
Are there overlapping genes in plants or animals?

I remember about overlapping genes in bacteriophages, but I though is was a weird trick because a big part of the bacteriophages is the DNA.

Re:DNA Mutations Do Not Occur Randomly – Discovery Transform... by dekhn on Sunday January 30, 2022 @10:09AM (#30137810)
yes, yeast have them. I think all organisms have some number of overlapping genes.
Re:DNA Mutations Do Not Occur Randomly – Discovery Transform... by gus_massa on Monday January 31, 2022 @10:44AM (#30149208)
Very interesting! I found this https://en.wikipedia.org/wiki/Overlapping_gene Do you have a better link? [Armchair biologist here :) .]
Re:DNA Mutations Do Not Occur Randomly – Discovery Transform... by dekhn on Monday January 31, 2022 @11:47AM (#30150064)
That's a great summary. If you want to go further, I think it's only really addressed in the literature and not much in textbooks.

The one interesting bit that I studied/researched and attempted to publish (no luck) was the observation that organisms that have RNAi, a process by which cells detect double-stranded RNA inside and eliminate it (likely a virus), tend to have fewer overlapping genes. When two different overlapping genes are transcribed to mRNA, they can form duplexes that kinda sorta look like viral RNA and get taken out by the RNAi surveillance system, even though they're legit transcripts.