Intrinsically Disordered Proteins- adaptation over deep time without NeoDarwinism


Intrinsically disordered proteins (IDPs) can maintain function over millions of years due to their intrinsic disorder regions (IDRs). It's now known IDP makes up the majority of proteins. Many feel that all proteins have some level of intrinsic disorder.

IDRs are characterized by their lack of a fixed three-dimensional structure, which allows them to be highly flexible and adaptable. This flexibility is essential for many IDP functions, such as signal transduction, molecular regulation, and protein-protein interactions.

One of the ways that IDRs contribute to the functional stability of IDPs over time is by allowing them to adapt more rapidly than structured proteins. This is because IDRs are less constrained by the need to maintain a specific structure, and therefore can tolerate more mutations without losing function. This directly challenges NeoDarwinian mutation models which claim increased mutations cause change.

Another way that IDRs contribute to the functional stability of IDPs is by allowing them to interact with a wide range of other proteins and molecules. This is because IDRs can adopt multiple different conformations, which allows them to bind to different targets with different affinities. This versatility is essential for many IDP functions, such as signal transduction and molecular regulation.

Finally, IDRs are often involved in post-translational modifications (PTMs), which are chemical changes that can alter the structure and function of proteins. PTMs can be used to regulate the activity of IDPs, and can also help to protect them from degradation. This makes IDRs even more robust to changes in the environment and over time.

Overall, IDRs play an important role in the functional stability of IDPs over millions of years. IDRs allow IDPs to be highly flexible and adaptable, to adapt rapidly, and to interact with a wide range of other proteins and molecules. All of these factors contribute to the ability of IDPs to maintain function over long periods of time outside of NeoDarwinian gradualism.

Here are some examples of IDPs that have maintained function over millions of years:

  • Histone proteins are IDPs that play a vital role in DNA packaging and gene regulation. Histone proteins have been shown to be highly conserved across a wide range of organisms, from bacteria to humans.

  • Transcription factors are IDPs that regulate the expression of genes. Transcription factors are also highly conserved across a wide range of organisms.

  • Signal transduction proteins are IDPs that transmit signals from the outside of the cell to the inside of the cell. Signal transduction proteins are essential for many cellular processes, such as cell growth and development.

These are just a few examples of the many IDPs that have maintained function over millions of years. IDPs play a vital role in many cellular processes, and their intrinsic disorder is essential for their functional stability.

The NonDarwinian process of GC bias maintains GC-enriched gene regions and are correlated with the amount of intrinsic disorder in proteins across species. This is because GC-rich codons are more likely to encode disorder-promoting amino acids.

There are a few reasons for this. First, GC-rich codons are more likely to encode amino acids with polar side chains, which are more likely to be exposed to the solvent and less likely to form stable interactions with other amino acids. Second, GC-rich codons are more likely to encode amino acids that are flexible and can adopt multiple conformations.

As a result, proteins with a high proportion of GC-rich codons are more likely to be disordered. This is especially true for proteins that are involved in signaling and regulation, as these proteins often need to be able to interact with a variety of different partners.

The correlation between GC-content and intrinsic disorder is present in all eukaryotes that have been studied, including humans, yeast, and plants. It is also present in bacteria, although the correlation is weaker.

This suggests that the relationship between GC-content and intrinsic disorder is a fundamental feature of protein evolution. It is possible that the high GC-content of disordered proteins is due to the fact that GC-rich codons are less likely to mutate, which can lead to the development of new protein functions.

It is also possible that the high GC-content of disordered proteins is due to the fact that GC-rich codons are more likely to be translated accurately, which is important for proteins that need to be able to interact with a variety of different partners.

The correlation between GC-content and intrinsic disorder is a fascinating example of how the composition of DNA can influence the structure and function of proteins.


GC-rich codons are more likely to encode amino acids with polar side chains. This is important for intrinsically disordered proteins (IDPs) because polar side chains can interact with water and other molecules, which helps to stabilize IDPs. IDPs are important for many cellular processes, such as signaling and regulation.

Here is a table of the GC-rich codons and the amino acids they encode:

| Codon | Amino acid | |---|---|---| | GCU | Alanine | | GCC | Alanine | | GCA | Alanine | | GCG | Alanine | | CGU | Arginine | | CGC | Arginine | | CGA | Arginine | | CGG | Arginine | | AGA | Arginine | | AGG | Arginine |

Four of these amino acids (alanine, arginine, histidine, and lysine) have polar side chains. This means that they can form hydrogen bonds with water, which helps to stabilize IDPs.

IDPs are important for many cellular processes because they are flexible and can interact with other proteins and molecules in many different ways. IDPs are also often involved in signaling and regulation, where they can play a role in turning genes on and off or controlling the activity of other proteins.

Overall, the fact that GC-rich codons are more likely to encode amino acids with polar side chains is important for IDPs because it helps to stabilize them and make them more functional.

Here are some examples of IDPs that are important for cellular processes:

  • P53: A tumor suppressor protein that helps to prevent cancer.

  • Histone proteins: Proteins that package DNA into chromatin.

  • Transcription factors: Proteins that regulate gene expression.

IDPs are also involved in many other cellular processes, such as cell signaling, protein folding, and metabolism.

The fact that intrinsically disordered proteins (IDPs) can maintain function over millions of years due to their intrinsic disorder regions (IDRs) challenges Neo-Darwinian gradual mutations.

Neo-Darwinian evolution proposes that new traits arise through the accumulation of small, random mutations that are then selected for or against by the environment. However, IDPs are often highly flexible and dynamic, and their function does not rely on a specific three-dimensional structure. This means that even large mutations to an IDR may not have a significant impact on its function.

For example, the IDR of the protein p53 is involved in a variety of functions, including tumor suppression and apoptosis. Mutations to this IDR are common in cancer, but many of these mutations do not affect the protein's function. This is because the IDR is able to maintain its flexibility and dynamics even when mutated.

The ability of IDPs to maintain function over long periods of time has been observed in a variety of organisms, including bacteria, plants, and animals. For example, a study of IDPs in the human proteome found that they are more likely to be conserved across different species than structured proteins.

This suggests that IDPs may play an important role in evolution, even though they do not fit into the Neo-Darwinian model of gradual mutations. One possibility is that IDPs allow for more rapid changes in protein function, which could be advantageous in rapidly changing environments.

Another possibility is that IDPs are more likely to develope new functions, as mutations to IDRs are less likely to disrupt the protein's existing function. This could help to explain the diversity of functions that IDPs play in biology.

Overall, the ability of IDPs to maintain function over long periods of time is a fascinating phenomenon that challenges our understanding of evolution. More research is needed to understand how IDPs develope and how they contribute to the diversity of life.

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