Natural Selections last stand- IDPs


The selection-mutation-drift (SMD) model (1991) is a theoretical model that describes the evolution of genes in a population. It takes into account the three main processes that can change the frequency of alleles in a population: natural selection, mutation, and genetic drift.

  • Natural selection is the process by which individuals with certain traits are more likely to survive and reproduce than individuals with other traits. This can lead to an increase in the frequency of the beneficial traits in the population over time.

  • Mutation is the process by which new genetic variants are created. Mutations can be either beneficial, neutral, or harmful. Beneficial mutations can increase the fitness of individuals and lead to their increased representation in the population. 

  • Genetic drift is the random change in allele frequencies in a population. This can happen due to chance events, such as the founder effect or the bottleneck effect.

The study below defeats the 30 year old selection-mutation-drift model. This model states that the frequency of synonymous codons is determined by the balance of selection for optimal codons and mutational drift. However, the study found that there is a strong negative correlation between codon usage scores and protein disorder, meaning that there is a preferential use of nonoptimal codons in regions predicted to be intrinsically disordered. This suggests that other factors, such as the need for rapid translation or the avoidance of mistranslation, are more important than natural selection for optimal codons in determining codon usage.

The study also found that the correlations between codon usage and protein disorder are conserved in other eukaryotes. This suggests that these correlations are not simply a consequence of the specific properties of Neurospora, but are a general feature of eukaryotic protein folding.

These findings have important implications for our understanding of protein folding. They suggest that codon usage is not simply a random process (SMD) but is instead influenced by the need to ensure proper protein folding. 

The SMD model may explain codon usage in some cases. For example, it is likely to be more important in genes that encode highly structured proteins. However IDP make up the majority of proteins ergo the SMD model does not work on the majority of proteins.

The article "Nonoptimal codon usage influences protein structure in intrinsically disordered regions" by Mian Zhou et al. (2015) investigates the relationship between codon usage and protein structure, with a particular focus on intrinsically disordered regions (IDRs). IDRs are regions of proteins that lack a well-defined secondary structure and are therefore often highly flexible and dynamic.

The authors first showed that there is a strong codon usage bias in the filamentous fungus Neurospora. They found that nonoptimal codons (i.e., codons that are less efficiently translated) are preferentially used in IDRs, while more optimal codons are used in structured domains. This suggests that codon usage may play a role in regulating the folding of IDRs.

To further investigate this, the authors performed structure-based codon manipulation of the Neurospora circadian clock gene frequency (frq). FRQ is a protein that contains both IDRs and structured domains. The authors found that codon optimization of the predicted disordered regions of FRQ impaired clock function and altered FRQ structures. These results suggest that nonoptimal codons in IDRs may play a functional role in regulating protein folding and function.

The authors also found that the correlations between codon usage and protein disorder tendency are conserved in other eukaryotes. This suggests that codon usage and protein structure co-evolve to ensure proper protein folding in eukaryotic organisms.

The findings of this study have important implications for our understanding of protein folding and function. They suggest that codon usage may be a previously unrecognized factor that regulates the folding of IDRs. This could lead to new strategies for engineering proteins with desired folding properties.

In addition, the findings of this study suggest that codon usage may be a potential target for the development of new therapeutic interventions. For example, codon optimization could be used to improve the folding of proteins that are misfolded in disease.

Overall, the study by Zhou et al. (2015) provides new insights into the relationship between codon usage and protein structure. These findings could have a significant impact on our understanding of protein folding and function, and could lead to new strategies for engineering and therapeutic interventions.

Here are some additional thoughts on the article:

  • The study provides strong evidence that codon usage can influence protein structure, especially in IDRs. This is a significant finding, as it suggests that codon usage is not just a neutral factor that affects translation efficiency, but can also have a direct impact on protein folding.

  • The study also provides evidence that codon usage and protein structure co-evolve. This suggests that there is a selective pressure for codon usage that is optimized for protein folding. This is an important finding, as it suggests that codon usage is not just a random process, but is instead actively regulated by the cell.

The study by Zhou et al. (2015) is an important contribution to our understanding of the relationship between codon usage and protein structure. The findings of this study could have a significant impact on our understanding of protein folding and function, and could lead to new strategies for engineering and therapeutic interventions.

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