IDP - more mutations with less evolution over billions of years


Intrinsically Disordered Proteins (IDP) can resist change over billions of years, but not because mutations don't change them. In fact, IDP are more susceptible to mutations than globular proteins. However, IDP have a number of features that allow them to tolerate mutations more easily.

One feature that makes IDP more tolerant of mutations is their lack of a fixed structure. Globular proteins have a specific three-dimensional structure that is essential for their function. If a mutation changes the structure of a globular protein, it can often render the protein non-functional. NeoDarwinism was developed not knowing IDP's existed. By neoDarwinism a beneficial mutation is envisioned that changes the globular protein in an advantageous manner for an improved phenotype for natural selection to select.


 But now we know the majority of proteins are IDP this has caused a rethink of NeoDarwinism.


IDP, on the other hand, do not have a fixed structure. They are more flexible and can tolerate a wider range of mutations without losing their function.

Another feature that makes IDP more tolerant of mutations is their ability to form transient interactions with other proteins. Globular proteins typically interact with other proteins through specific binding sites. If a mutation changes the structure of a binding site, it can prevent the protein from interacting with its partner protein.  This was an open question with NeoDarwinism mainly how beneficial mutations out pace the more probable harmful mutations. On the other hand, IDPs can interact with other proteins through a variety of different mechanisms. This makes them less dependent on specific binding sites and more tolerant of mutations.

As a result of these features, IDP can resist change over billions of years. They are more susceptible to mutations than globular proteins, but they are also more tolerant of mutations. This allows them to evolve more slowly and to retain their function even in the face of environmental changes. This is counter intuitive to the NeoDarwinian mutational model as we have increased mutations with little effect.

Here are some additional details about the features of IDP that make them tolerant of mutations:

  • Low sequence complexity: IDP typically have a low sequence complexity, meaning that they have a repetitive amino acid sequence. This makes them less susceptible to mutations that change the amino acid sequence.

  • High flexibility: IDP are highly flexible, meaning that they can change their shape easily. This allows them to tolerate mutations that would disrupt the structure of a globular protein.

  • Ability to form transient interactions: IDP can form transient interactions with other proteins. This means that they do not need to have specific binding sites to interact with other proteins. This makes them less dependent on specific amino acids and more tolerant of mutations.

IDP play a variety of important roles in cells, including:

  • Regulating gene expression: IDP can bind to DNA and RNA and regulate gene expression.

  • Signaling: IDP can transmit signals between cells and within cells.

  • Cell adhesion: IDP can help cells to adhere to each other and to the extracellular matrix.

  • Enzyme activity: IDP can act as enzymes and catalyze chemical reactions.

IDP can act outside of neo darwinism in a number of ways. For example, they can:

  • Play a role in epigenetics: Epigenetic changes are changes in gene expression that are not caused by changes in the DNA sequence. IDP can help to regulate epigenetic changes, which can have a significant impact on the phenotype of an organism.

  • Contribute to phenotypic plasticity: Phenotypic plasticity is the ability of an organism to change its phenotype in response to environmental changes. IDP can help to mediate phenotypic plasticity, which can allow organisms to adapt to new environments.

  • IDP can be involved in a variety of processes, such as adaptation, and gene regulation.

Here are some specific examples of how IDP can act outside of neo darwinism:

  • In epigenetics: IDP can bind to DNA and RNA and regulate the expression of genes. This can be done by changing the structure of DNA, by recruiting other proteins to the DNA, or by blocking the binding of other proteins to the DNA.

  • In phenotypic plasticity: IDP can help cells to respond to changes in their environment. For example, IDP can help cells to sense changes in temperature, light, or nutrient availability. They can also help cells to respond to changes in the levels of hormones or other signaling molecules.

  • In evolutionary processes: IDP can be involved in a variety of processes. They can also help to promote adaptation, by allowing organisms to evolve new traits in response to environmental changes.

IDP are a fascinating class of proteins that are still being studied. Their unique properties make them well-suited for a variety of different roles in cells, including those that fall outside of the traditional neo-Darwinian paradigm.


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