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Many "silent" DNA mutations could be harmful - scary stuff!


jimmydasaint

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The DNA code can have changes in it called mutations. DNA sequences specifically codes for amino acid sequences which are built into proteins. Proteins control the development  of organisms from a starting point to final organism itself. 

If the DNA mutations are in areas of the DNA code which can cause changes in the amino acid sequence, the final protein could be faulty and affect the final organism. Diseases such as  Sickle cell anaemia or cystic fibrosis are caused by a harmful DNA mutation arising from a single letter change in the DNA  sequence. 

I have grown up, and taught to my A-level (K12/13) students that some DNA mutations which do not affect the amino acid sequence are "neutral", "silent" or harmless. 

To my surprise, I read this recently and wanted to share it. 

Quote

 

Most 'silent' genetic mutations are harmful, not neutral -- a finding with broad implications

Date:

June 8, 2022

Source:

University of Michigan

Summary:

Occasionally, single-letter misspellings in the genetic code, known as point mutations, occur. Point mutations that alter the resulting protein sequences are called nonsynonymous mutations, while those that do not alter protein sequences are called silent or synonymous mutations. Between one-quarter and one-third of point mutations in protein-coding DNA sequences are synonymous. Those mutations have generally been assumed to be neutral, or nearly so. A new study involving the genetic manipulation of yeast cells shows that most synonymous mutations are strongly harmful.

 

ScienceDaily

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I'm merely a student of evolutionary biology but this article reads like an alarmist piece. And because it's not peer reviewed it carries no weight with me. I suspect were it presented for scrutiny we would find that most mutations are harmless and any harmful ones eliminated quickly. If the opposite were true many species would be seriously hindered since only a limited amount of offspring would survive to reach sexual maturity. Perhaps humans have found a way to increase harmful variations within our own genus but it's only because those born with defects in fitness reach sexual maturity instead of being eliminated. If natural selection is not permitted to function the fitness of any species will suffer.

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On 8/6/2022 at 10:11 PM, JimBlob said:

I'm merely a student of evolutionary biology but this article reads like an alarmist piece. And because it's not peer reviewed it carries no weight with me. I suspect were it presented for scrutiny we would find that most mutations are harmless and any harmful ones eliminated quickly. If the opposite were true many species would be seriously hindered since only a limited amount of offspring would survive to reach sexual maturity. Perhaps humans have found a way to increase harmful variations within our own genus but it's only because those born with defects in fitness reach sexual maturity instead of being eliminated. If natural selection is not permitted to function the fitness of any species will suffer.

More genetic diversity is really a good thing. Shows that we're starting to recover from the genetic bottlenecks that we've been through as a species.

Who knows what mutations might be required in the future?

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On 8/7/2022 at 3:11 AM, JimBlob said:

I'm merely a student of evolutionary biology but this article reads like an alarmist piece. And because it's not peer reviewed it carries no weight with me. I suspect were it presented for scrutiny we would find that most mutations are harmless and any harmful ones eliminated quickly. If the opposite were true many species would be seriously hindered since only a limited amount of offspring would survive to reach sexual maturity. Perhaps humans have found a way to increase harmful variations within our own genus but it's only because those born with defects in fitness reach sexual maturity instead of being eliminated. If natural selection is not permitted to function the fitness of any species will suffer.

It's good that you are reading with a critical eye. This will serve your studies well. The studies were performed on the yeast Saccharomyces cerevisiae, and the authors assumed that a wider number of species would show similar trends. As far as the article being peer-reviewed, if you had read to the end of the Science Daily article you would found the following reference:

Quote

Journal Reference:

  1. Xukang Shen, Siliang Song, Chuan Li & Jianzhi Zhang. Synonymous mutations in representative yeast genes are mostly strongly nonneutral. Nature, 2022 DOI: 10.1038/s41586-022-04823-w

I hope that the journal Nature is stringent and peer-reviewed enough for your liking as it is quite well known. I think the research and the conclusions are not alarmist but quite pragmatic and, if they are found reproducible from a number of different scientists, overturn my old fuddy-duddy beliefs about so-called neutral mutations.  

On 8/14/2022 at 5:41 PM, GREYEANNIUS said:

Perhaps time is of essense. Old news sometimes lightens up to new news. sorry :(

Thanks for the reply. The news was published in 2022 and is quite dramatic. If proved, Biology books at school level would have to rewrite sections on genetic mutations. 

Edited by jimmydasaint
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I don't get why this should be a surprise. If you think about your own genome, all of it originated with a mutation. And they all proved beneficial at the time, otherwise they would not have persisted in the population. So what you've ended up with is a genome of the best available genes, and the worse ones have disappeared over the ages. 

So if a mutation occurs, it's up against a collection of elite genes, and the chances are low that it will be better than the established genes. They have thousands or millions of years of selection in their favour. So the mutation's chances of being better just by chance is pretty low. 

Of course, it's more complicated than that, and it's gene combinations that sometimes count, but the principle still remains. I would expect most mutations to be less fit than the predecessor. 

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