Disordered Proteins escape NeoDarwnianism

Intrinsically disordered proteins (IDPs) are proteins that don't have a fixed shape. They are flexible and can change shape to interact with other molecules. IDPs are involved in many important cellular processes, such as signaling, regulation, and transport. 

IDP have only recently (10 years) been discovered to make up the majority of proteins.

Intrinsically disordered proteins (IDRs) are more resistant to mutation effects over billions of years than ordered proteins. This is because IDRs are less structured and have more flexibility than ordered proteins. This flexibility allows IDRs to accommodate mutations without disrupting their function.

The structured sequence hypothesis was first proposed by Francis Crick in 1958. It states that the sequence of bases in the genetic material (DNA or RNA) determines the sequence of amino acids for which that segment of nucleic acid codes, and this amino acid sequence determines the three-dimensional structure into which the protein folds. The three-dimensional structure of a protein is required for a protein to be functional.

This became the key cornerstone of Neo-Darwinism. 

Evolution occurred when a random mutation caused a change in the protein structure. If an improvement occurred natural selection would fix it in place. 

And so we thought for 50 years.

IDRs are also more likely to have a high GC bias, which means that they have a higher proportion of guanine and cytosine nucleotides than adenine and thymine nucleotides. gBGC>GC bias is a natural cellular mechanism.

GC-rich regions of DNA are more resistant to mutation than AT-rich regions, because GC base pairs have 3 hydrogen bonds as oppose to 2 for AT pairs thus are more stable.

The resistance of IDRs to mutation challenges neo-Darwinism, which is the theory that evolution is driven by natural selection acting on random mutations. Neo-Darwinism predicts that mutations that are harmful to an organism will be eliminated by natural selection, while mutations that are beneficial will be passed on to future generations.

However, the resistance of IDRs to mutation suggests that some harmful mutations can be tolerated, and even passed on to future generations. This is because IDRs are able to accommodate mutations without disrupting their function.

The resistance of IDRs to mutation also suggests that GC bias can play a role in NonDarwinian outside of natural selection. GC bias can help to protect IDRs from harmful mutations, which can allow them to retain their function over long periods of time.

Researchers are still learning about the role of IDRs in evolution. However, the evidence suggests that IDRs are important players in the DNA, and that their resistance to mutation has helped to shape the genomes of living organisms.

The article "Protein condensates as flexible platforms for membrane traffic" by Anna I. Buchan and Anthony A. Hyman, published in the journal Current Opinion in Cell Biology in 2023, discusses the role of protein condensates in membrane trafficking.

Protein condensates are dynamic, liquid-like assemblies of proteins that can form in cells. They are thought to play a role in a variety of cellular processes, including membrane trafficking.

Membrane trafficking is the process by which molecules are transported between different compartments within a cell. It is a complex process that involves a variety of proteins.

Protein condensates are thought to act as flexible platforms for membrane trafficking. They can provide a site for the assembly of proteins involved in membrane trafficking. They can also help to direct the movement of vesicles, which are small sacs that transport molecules between different compartments within a cell.

The article discusses a number of recent studies that have shed light on the role of protein condensates in membrane trafficking. For example, one study showed that protein condensates are involved in the trafficking of vesicles to the plasma membrane, which is the outer membrane of the cell. Another study showed that protein condensates are involved in the trafficking of vesicles between the Golgi apparatus and the endoplasmic reticulum, which are two organelles that are involved in the processing and packaging of proteins.

The authors of the article conclude that protein condensates are important regulators of membrane trafficking. They suggest that further research on protein condensates could lead to new insights into membrane trafficking and new therapeutic strategies for diseases that affect membrane trafficking.

Protein condensates are multivalent protein assemblies that can form and dissolve rapidly, and they are often enriched in intrinsically disordered proteins (IDPs). IDPs lack a well-defined secondary structure, which allows them to interact with other proteins and membranes in a dynamic way.

The authors argue that protein condensates play a critical role in membrane trafficking by providing flexible platforms for the assembly and disassembly of trafficking vesicles. Membrane trafficking is the process by which lipids and proteins are transported throughout the cell, and it is essential for many cellular functions, such as cell signaling, metabolism, and waste disposal.

The authors provide several examples of how protein condensates are involved in membrane trafficking. For example, protein condensates are involved in the initiation of endocytosis, the process by which cells internalize molecules from the outside world. Protein condensates also play a role in the sequestration of synaptic vesicles, which are the vesicles that store and release neurotransmitters. Additionally, protein condensates are involved in the stabilization of endoplasmic reticulum exit sites, where proteins are transported from the endoplasmic reticulum to the Golgi apparatus.

The authors conclude by discussing some of the open questions in the field. For example, it is not yet fully understood how protein condensates assemble and disassemble, or how they interact with membranes. Additionally, it is not clear how protein condensates contribute to specific membrane trafficking steps.

Overall, the article provides a good overview of the emerging role of protein condensates in membrane traffic. It is clear that protein condensates play a critical role in this essential cellular process, and further research is needed to understand their precise mechanisms of action.