A new study finds that most "silent" mutations are harmful rather than neutral:
Marshall Nirenberg, a University of Michigan alumni, and a small group of researchers cracked the genetic code of life in the early 1960s, figuring out the rule by which information stored in DNA molecules is converted into proteins, the functional components of living cells.
They discovered three-letter DNA units called codons that describe each of the 20 amino acids that make up proteins. This discovery would win Nirenberg and two others the Nobel Prize.
Occasionally, single-letter misspellings in the genetic code, known as point mutations, occur. Nonsynonymous mutations are point modifications that alter the protein sequences that result from them, while silent or synonymous mutations do not change the protein sequences.
[...] “Since the genetic code was solved in the 1960s, synonymous mutations have been generally thought to be benign. We now show that this belief is false,” said study senior author Jianzhi “George” Zhang, the Marshall W. Nirenberg Collegiate Professor in the U-M Department of Ecology and Evolutionary Biology.
“Because many biological conclusions rely on the presumption that synonymous mutations are neutral, its invalidation has broad implications. For example, synonymous mutations are generally ignored in the study of disease-causing mutations, but they might be an underappreciated and common mechanism.”
[...] Zhang said the researchers knew beforehand, based on the anecdotal reports, that some synonymous mutations would likely turn out to be nonneutral.
“But we were shocked by the large number of such mutations,” he said. “Our results imply that synonymous mutations are nearly as important as nonsynonymous mutations in causing disease and call for strengthened effort in predicting and identifying pathogenic synonymous mutations.”
The U-M-led team said that while there is no particular reason why their results would be restricted to yeast, confirmations in diverse organisms are required to verify the generality of their findings.
Reference: “Synonymous mutations in representative yeast genes are mostly strongly non-neutral” by Xukang Shen, Siliang Song, Chuan Li, and Jianzhi Zhang, 8 June 2022, Nature. DOI: 10.1038/s41586-022-04823-w
(Score: 2) by bzipitidoo on Monday August 29 2022, @01:33PM (7 children)
Lot of wrong ideas floating around. Like the idea that a significant proportion of DNA is "junk". Another one, that random mutations could be a driver of evolution because a very few turn out to be good. These never made much sense intuitively. Change one character at random in some source code (that doesn't have comments), and you've almost certainly broken the program. The possibilities are all pretty bad. Maybe the program still starts, and even functions for a while, until the affected section is used, then it crashes. Or, it could fail in other ways, such as, producing bad data. The program could even finish, but output garbage. About the best that can happen is that some unimportant data was changed, perhaps a pixel of an icon was changed to a different color, and thus the program was not materially affected.
(Score: 2, Insightful) by shrewdsheep on Monday August 29 2022, @02:07PM (2 children)
I seem to be a supporter of these "wrong ideas". To get to your point of random mutations: keep in mind that DNA is not "programmed" the same way computer programs are. While there seem to be examples of lethal mutaions, the DNA "program" is quite resistant to accruing mutations. We accrue mutations every millisecond and keep alive while we speak. One reason is DNA is like raw silicon: everythings runs in parallel. Any functional path can choose the best set of proteins to run along and if one breaks, other sets of proteins can compensate.
I'm curious: if not for random mutations, what is driving evolution in your opinion?
(Score: 3, Interesting) by bzipitidoo on Monday August 29 2022, @06:14PM
What I suspect is that we don't fully appreciate biology. I realize that's a bold thing to say. We know DNA is a physical medium for information. We know a lot less about how that information is utilized. Most of all, we don't much know how biological systems modify it, expanding-- or sometimes contracting-- the plans for building a living organism, in a way that can evolve. We are barely able to make the connection between specific sections of DNA and various conditions.
To suppose that evolution happens through chance mutation is simply not credible. No. What's happening is that individuals all have minor variations between one another. Variations that confer net advantages are naturally expanded upon. It takes an awful lot of incremental changes over a very long time, but eventually, the cumulative change is so great that the organism qualifies as a separate species, and can no longer breed with the ancestor from which they diverged. Another method is DNA transfer between organisms of different species. Bacteria, I understand, do that quite often. Multicellular organisms, not so much.
Decades ago, some seriously thought that Roman engineers just got lucky. Was mere luck that the aqueducts worked, and lasted. Didn't believe Roman tech and knowledge was up to the job of calculating exactly how steep to slope them, and that therefore they had to resort to lots of trial and error, intuition, and luck. That notion has been thoroughly debunked. Roman engineers knew how to get it right the first time.
(Score: 3, Funny) by darkfeline on Friday September 02 2022, @01:08AM
So you're saying computer programs aren't written by randomly copying and mutating snippets of code? StackOverflow would like to have a word.
Join the SDF Public Access UNIX System today!
(Score: 3, Interesting) by Common Joe on Monday August 29 2022, @03:35PM (3 children)
The idea that most mutations are harmful was always silly. If most mutations were harmful, we wouldn't be able to build up such a diverse ecosystem of plants and animals. At worst (and probably best), we can say a collection of mutations are neutral. The few collections of mutations that are better will float to the top and spread around under Darwinism. Thus, we have evolution.
If most mutations were a net negative, we'd have a downward trend of mutations (which might include a few spikes of improvements, but not enough to offset the negatives). We would de-evolve into nothing.
(Score: 3, Informative) by bloodnok on Monday August 29 2022, @06:49PM (2 children)
You're missing the power of natural selection. If a mutation is, or becomes, harmful your chances of having successful progeny are reduced. Harmful mutations are mostly selected against.
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The major
(Score: 2) by Common Joe on Tuesday August 30 2022, @02:34AM (1 child)
I wasn't trying to fully define our current understanding of evolution. (I wouldn't be qualified anyway.) And my point wasn't about harmful vs beneficial mutations. You're correct in that evolution of an organism depends upon its environment. (It's the environment which defines whether a mutation is harmful or not.)
My point is purely a thought experiment (because it can't exist in the real world): If the environment is neutral towards an organism, and the organism can survive with it's neutral mutation, the net result is that it's easier for a mutation to de-evolve than to evolve. An example: It's easier to de-evolve an eyeball rather than to create one through purely random mutations. A "monkeys writing Shakespeare" kind of thing. Because of this, all organisms would de-evolve in the long run. Bigger organisms would lose the ability to see, hear, taste, etc. Smaller organisms like cells would simply lose the ability to hold themselves together.
(Score: 2) by Common Joe on Tuesday August 30 2022, @03:06AM
Ugh. Forgive me. I'm really tired. It looks like I just argued against myself. But both of my comments can still fit together, though. And now I'll try to address your comment, bloodnok.
In a neutral environment, we would de-evolve... into nothing. I'll rephrase this: Most mutations are harmful in a neutral environment which is achieved only in a thought experiment.
But we aren't in a neutral environment. We're in a closed environment. If evolution was more harmful, we wouldn't have life on this planet at all; if life were dropped on a planet in a neutral environment, it would de-evolve. Things like eyeballs would go away and cells would eventually go away too. Thus, it's pretty clear that evolution (which takes into account the environment) is not harmful to life. Evolution pushes changes in a net positive direction for a given environment, but that environment changes as soon as you get that new organism with that new mutation.
You know what, I don't feel I'm making any sense here nor converging on any point I want to make. It seems my ability to respond to your comment just falls flat. Unfortunately, I can't go back to sleep either because I have to get ready for work. I'll just give up and pretend to be awake at my work environment. I hope my mutations allow me to be more coherent there so no one notices I'm asleep.
(Score: 1) by unhandyandy on Tuesday August 30 2022, @02:22AM
Can someone explain to me, like I'm a HS student, why synonymous mutations could ever be harmful? TFA says that " both synonymous and nonsynonymous mutations alter the gene-expression level" but how is that possible, if synonymous mutations don't affect the protein sequencing?