Example of neutral accumulation of biological complexity via evolution

[pitabread]

A new study at the University of Chicago has shown that elaborate protein structures accumulate over deep time even when they serve no purpose, because a universal biochemical property and the genetic code force natural selection to preserve them. The work was published on Dec. 9, 2020 in Nature.

Most proteins in our cells form specific complexes with other proteins, a process called multimerization. Like other kinds of complexity in biology, multimers are usually thought to persist over evolutionary time because they confer some functional benefit that is favored by natural selection.

...

The researchers showed that simple biochemical, genetic and evolutionary principles make entrenchment of molecular complexes inevitable. The genes that code for every protein are subject to a constant hail of mutations over generations, many of which would disrupt the protein's ability to fold up and function properly. A form of natural selection called purifying selection removes these deleterious mutations from the population.

Once a protein evolves to multimerize, the parts that form the interface can accumulate mutations that would be deleterious if the protein were in the solo state, so long as they can be tolerated in the multimer. Purifying selection then entrenches the complex form, preventing a return to the solo state.

The researchers showed that a simple and universal rule of biochemistry underlies entrenchment. Proteins are made up of amino acids, which may be water soluble, or hydrophobic, meaning they dissolve easily in oil but not water. Usually, proteins fold so the water-soluble amino acids are on the outside and the hydrophobic amino acids are on the inside. Mutations that make a protein's surface more oil soluble impair its folding, so purifying selection removes them if they occur in solo proteins.

If the protein evolves to multimerize, however, those hydrophobic amino acids on the interface surface are hidden from water, and become invisible to purifying selection. The multimer is then entrenched, because returning to the solo state would expose the now-oil-soluble and deleterious interface.​

Story here: A simple rule drives the evolution of useless complexity: New study shows that proteins become biochemically addicted to complex interactions without adaptation.

Paper here: A hydrophobic ratchet entrenches molecular complexes | Nature

​

This actually seems like another example of how the evolution of irreducible complexity, whereby a pathway to a more complex state followed by mutation prevents a return to a simpler state.

What is especially fascinating about this example is it doesn't seem driven by beneficial mutations, but as the article describes, selective pressures relative to deleterious mutations.

 

[inquiring mind]

A new study at the University of Chicago has shown that elaborate protein structures accumulate over deep time even when they serve no purpose, because a universal biochemical property and the genetic code force natural selection to preserve them. The work was published on Dec. 9, 2020 in Nature.

Most proteins in our cells form specific complexes with other proteins, a process called multimerization. Like other kinds of complexity in biology, multimers are usually thought to persist over evolutionary time because they confer some functional benefit that is favored by natural selection.

...

The researchers showed that simple biochemical, genetic and evolutionary principles make entrenchment of molecular complexes inevitable. The genes that code for every protein are subject to a constant hail of mutations over generations, many of which would disrupt the protein's ability to fold up and function properly. A form of natural selection called purifying selection removes these deleterious mutations from the population.

Once a protein evolves to multimerize, the parts that form the interface can accumulate mutations that would be deleterious if the protein were in the solo state, so long as they can be tolerated in the multimer. Purifying selection then entrenches the complex form, preventing a return to the solo state.

The researchers showed that a simple and universal rule of biochemistry underlies entrenchment. Proteins are made up of amino acids, which may be water soluble, or hydrophobic, meaning they dissolve easily in oil but not water. Usually, proteins fold so the water-soluble amino acids are on the outside and the hydrophobic amino acids are on the inside. Mutations that make a protein's surface more oil soluble impair its folding, so purifying selection removes them if they occur in solo proteins.

If the protein evolves to multimerize, however, those hydrophobic amino acids on the interface surface are hidden from water, and become invisible to purifying selection. The multimer is then entrenched, because returning to the solo state would expose the now-oil-soluble and deleterious interface.​

Story here: A simple rule drives the evolution of useless complexity: New study shows that proteins become biochemically addicted to complex interactions without adaptation.

Paper here: A hydrophobic ratchet entrenches molecular complexes | Nature

​

This actually seems like another example of how the evolution of irreducible complexity, whereby a pathway to a more complex state followed by mutation prevents a return to a simpler state.

What is especially fascinating about this example is it doesn't seem driven by beneficial mutations, but as the article describes, selective pressures relative to deleterious mutations.

Not even the University of Chicago can say what definitely (100%) happens over deep time. They were smart enough to use ‘could,’ ‘may,’ ‘possibly’ (50% chance) and ‘probably’ (75% chance) appropriately though.

 

[pitabread]

Not even the University of Chicago can say what definitely (100%) happens over deep time. They were smart enough to use ‘could,’ ‘may,’ ‘possibly’ (50% chance) and ‘probably’ (75% chance) appropriately though.

Do you have anything to say about the findings themselves?

 

[QvQ]

Do you have anything to say about the findings themselves?

"What is especially fascinating about this example is it doesn't seem driven by beneficial mutations, but as the article describes, selective pressures relative to deleterious mutations." (I added your quote manually as I don't know how to make multiple quotes)

From what I understand, if this is the same mutation, it is extremely deleterious as I believe the proteins that cannot be degraded due to this mutation inducing multimerization would be drusen, which is what causes blindness in macular degeneration and some other eye diseases.

This is the only disease I have researched concerning multimerization so maybe the article you posted refers to something else;

" By directly measuring the turnover of TIMP-3 and SFD-TIMP-3 protein in the matrix of human RPE cells, we show that in all cases mutation induces multimerization, rendering a proportion of the SFD proteins resistant to degradation and providing a mechanism for TIMP-3 accumulation in the disease."

"SFD and DHRD are monogenic diseases caused by mutations in TIMP3 and EFEMP1 genes, respectively. Histopathologic studies on donor eyes of both SFD and DHRD patients have shown abnormal lipid- and protein-rich sub-RPE deposits (drusen)"

 

[Tolworth John]

What they are basically saying is that inside a written chapter there can be a paragraph that makes no sense to the reader but the use of symbols like ' ( ' and ' ) ' prevent that paragraph being editted out.

The problem is, how does the random accumulation of words and letters actually become something that makes grammatical sense, together with how is this grammatical correct paragraph inserted into the book where it will still make grammatical sense.

 

[QvQ]

"It is therefore likely that many protein complexes persist because a simple ratchet-like mechanism entrenches them across evolutionary time, even when they are functionally gratuitous."

The problem with drusen is that it appears so late in life the mutation is unlikely to be winnowed out by selection.
I am really pleased to see this research because if the accumulations are understood, then how to untie that knot, that "ratchet - like mechanism that entrenches" proteins and solve the problem of "drusen" by some mechanical operation then wet and dry macular degeneration might be successfully treatable.

Thanks for posting this, very informative!

 

[FrumiousBandersnatch]

What they are basically saying is that inside a written chapter there can be a paragraph that makes no sense to the reader but the use of symbols like ' ( ' and ' ) ' prevent that paragraph being editted out.

The problem is, how does the random accumulation of words and letters actually become something that makes grammatical sense, together with how is this grammatical correct paragraph inserted into the book where it will still make grammatical sense.

Because DNA isn't like a book. If anything, it's more like a recipe where genes code for the ingredients, and in these cases, by analogy, some of the ingredients that would otherwise tend to go off get bound to preservatives that prolong their life - even when they don't usefully contribute to the cake...