GC bias of IDPs keeps evolution away for billions of years


The paper "Evolutionary Forces and Codon Bias in Different Flavors of Intrinsic Disorder in the Human Proteome" investigates the evolutionary forces that shape the codon usage bias of human genes encoding proteins characterized by different flavors of intrinsic disorder (IDPs).

The authors found that IDPs are preferentially encoded by GC-rich genes, which is consistent with the fact that GC-rich genes are more tolerant to mutations. This defeats the random mutation model of NeoDarwinism. They also found that IDPs are characterized by the highest fraction of CpG sites in the sequences, which implies that they are more susceptible to epigenetic methylation resulting in C-T transition mutations.

The authors also found that codon usage in IDPs is affected by a basic mutational bias not darwinian random mutations.

The authors speculate that this pressure may be due to the fact that IDPs have a high tolerance to mutations and can still function even if they are slightly altered. This allows them to adapt more rapidly than well-folded proteins, which are more sensitive to mutations. Therefore IDPs can maintain function over billions of years despite mutations. This is in direct opposition to Neo Darwinism. According to it evolution occurs by increased numbers of mutations. IDPs maintain function over billions of year's despite mutations.

The authors' findings provide new insights into the evolutionary forces that shape the codon usage bias of IDPs. They also suggest that IDPs play an important role in the evolutionary adaptability and evolvability of proteins.

Here are some additional thoughts on the paper:

  • The authors' findings suggest that there is a trade-off between the structural stability and evolutionary adaptability of proteins. Well-folded proteins are more structurally stable, but they are also more sensitive to mutations. IDPs are less structurally stable, but they are more tolerant to mutations and can adapt more rapidly.

  • The authors' findings also suggest that the evolutionary forces that shape the codon usage bias of proteins are complex and can vary depending on the protein's function and structure.

  • IDPs are increasingly being recognized as playing important roles in a variety of biological processes, including protein folding, regulation, and signaling. The authors' findings provide new insights into the evolutionary mechanisms that underlie the function and evolution of IDPs.

Article Snippets

Well-structured proteins are expected to be more under control by purifying natural selection than intrinsically disordered proteins because one or few mutations (even synonymous) in the genes can result in a protein that no longer folds correctly.

intrinsically disordered proteins are thought to adapt more rapidly than well-folded proteins, due to an increased role of mutational bias.

codon usage in IDPs is affected by a basic mutational bias.

We speculate that intrinsically disordered proteins have not only a high tolerance to mutations but also a propensity to preserve their structural disorder under physiological conditions.

Well-structured proteins are expected to be more under control by purifying natural selection than intrinsically disordered proteins because one or few mutations (even synonymous) in the genes can result in a protein that no longer folds correctly.

we confirm not only that intrinsically disordered proteins are preferentially encoded by GC-rich genes, but also that they are characterized by the highest fraction of CpG sites in the sequences, implying a higher susceptibility to methylation resulting in C–T transition mutations.

On the contrary, intrinsically disordered proteins are thought to adapt more rapidly than well-folded proteins due to the increased role of mutational bias.

our results corroborate the essential role of intrinsic disorder for the evolutionary adaptability and evolvability of proteins, offering new insight about protein evolution not only in terms of functional properties and roles in diseases but also in terms of evolutionary forces they are subjected to.

we find evidence that codon usage in IDPs is not only affected by a basic mutational bias, but it is also more constrained than the rest of the human proteome.

We speculate that intrinsically disordered proteins have not only a high tolerance to mutations but also a selective propensity to preserve their structural disorder under physiological conditions.

Additionally, we confirm not only that intrinsically disordered proteins are preferentially encoded by GC-rich genes, but also that they are characterized by the highest fraction of CpG sites in the sequences, implying a higher susceptibility to methylation resulting in C–T transition mutations

Overall, our results corroborate the essential role of intrinsic disorder for the evolutionary adaptability and evolvability of proteins, offering new insight about protein evolution not only in terms of functional properties and roles in diseases but also in terms of evolutionary forces they are subjected to.

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