Phenotype Bias of RNA Structures outside of Neo-Darwinism

The article "Phenotype Bias Determines How Natural RNA Structures Occupy the Morphospace of All Possible Shapes" by Dingle et al. (2023) investigates how the set of all possible RNA secondary structure (SS) shapes is populated in nature. 

The authors argue that a strong phenotype bias, which limits evolutionary dynamics to a subset of structures that are easy to "find," is the primary explanation for this pattern. Phenotype bias is the tendency of certain phenotypes to arise more readily than others due to the constraints of development. It is also referred to as developmental bias.

To support their argument, Dingle et al. use a combination of theoretical and computational methods. They first show that the number of possible RNA SS shapes is extremely large, far exceeding the number of shapes that have been observed in nature. 

RNA SS shapes, or RNA secondary structure shapes, are the two-dimensional representations of RNA molecules. They are derived from the base pairing interactions between complementary nucleotides in the RNA sequence. RNA SS shapes are important because they can influence the function of RNA molecules, such as their ability to interact with proteins and other RNAs.

They then use a random sampling approach to show that only a small fraction of the possible shapes are easily accessible from random RNA sequences. This suggests that the vast majority of possible RNA SS shapes are unlikely to be found in nature, even given enough evolutionary time.

Dingle et al. also show that the distribution of RNA SS shapes in nature is highly skewed, with only a few shapes being very common and many shapes being very rare. This pattern is consistent with the presence of a strong phenotype bias.

The authors conclude that phenotype bias is the primary explanation for how RNA SS shapes occupy the morphospace of all possible shapes. A morphospace is a representation of the possible forms, shapes, or structures of an organism. They also argue that their findings have implications for understanding the evolution of RNA and other biological systems.

Specifically, the authors' findings suggest that:

• Only the most frequent RNA SS shapes appear in nature.

• The vast majority of possible RNA SS shapes in the morphospace have not yet been explored.

• Remarkably small numbers of random sequences are needed to produce all the RNA SS shapes found in nature so far.

• Perhaps most surprisingly, the natural RNA SS shapes are not evenly distributed in the morphospace. Instead, they are clustered in a few regions, suggesting that there is a strong phenotype bias towards certain shapes.

The authors' findings are important because they provide a new perspective on how RNA SS shapes evolve. 

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The article challenges neo-Darwinism in a number of ways.

First, the article provides evidence that the distribution of RNA structures in nature is not random, but is instead biased towards certain shapes. This suggests that the evolutionary process is not simply a matter of natural selection acting on random mutations, but is also influenced by the underlying physical and chemical constraints on RNA folding.

Second, the article shows that this phenotype bias can have a significant impact on the rate and direction of evolution. For example, the authors show that RNA structures that are biased towards certain shapes are more likely to evolve new functions. This is because these structures are more likely to be compatible with other RNA molecules and proteins, and are also more likely to be able to perform new tasks.

Third, the article suggests that phenotype bias can help to explain some of the major patterns of evolution, such as the repeated evolution (homoplasy) of similar structures in different lineages. For example, the authors show that the same RNA folds are often used to build different types of enzymes, even in organisms that are only distantly related. This suggests that these folds are particularly well-suited for performing certain tasks, and that they are therefore more likely to evolve independently in different lineages.

Overall, the article provides strong evidence that phenotype bias plays an important role in NonDarwinian evolution. This challenges the traditional neo-Darwinian view of evolution as a purely random process. Instead, the article suggests that evolution is a more complex process that is influenced by a variety of factors, including phenotype bias.

Here are some specific examples of how the article challenges neo-Darwinism:

• Neo-Darwinism typically assumes that mutations are random with respect to their phenotypic effects. However, the article shows that mutations in RNA are more likely to occur in certain regions of the genome, and that these regions are more likely to produce RNA structures with certain shapes. This suggests that mutations are not truly random, and that they can be biased towards certain phenotypes.

• Neo-Darwinism also typically assumes that natural selection is the only force that drives evolution. However, the article shows that phenotype bias can also influence the rate and direction of evolution. This suggests that evolution is a more complex process than neo-Darwinism typically assumes.

• Neo-Darwinism has difficulty explaining the repeated evolution of similar structures in different lineages. However, the article shows that phenotype bias can help to explain this phenomenon. This suggests that phenotype bias is a more important force in evolution than neo-Darwinism typically assumes.

Overall, the article provides a significant challenge to the traditional neo-Darwinian view of evolution. It suggests that evolution is a more complex process that is influenced by a variety of factors, including phenotype bias.

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Article snippets

Here we demonstrate quantitatively that developmental bias is the primary explanation for the occupation of the morphospace of RNA secondary structure (SS) shapes.

The ultimate cause of these patterns is not natural selection, but rather a strong phenotype bias in the RNA genotype–phenotype map, a type of developmental bias or “findability constraint,” which limits evolutionary dynamics to a hugely reduced subset of structures that are easy to “find.”

Much of evolutionary theory has focused on this second step. By contrast, the study of variation has been relatively underdeveloped.

If there are strong anisotropic developmental biases, then structure in the arrival of variation may well play an important explanatory role in the biological phenomena we observe today.

The fundamental reason for the anisotropic occupation of a morphospace could simply be some form of contingency.

noncoding RNA (ncRNA) found in nature populates the morphospace of all possible RNA SS shapes.

This system thus provides, to our knowledge, the cleanest evidence yet for developmental bias strongly affecting evolutionary outcomes.

An important question for future work will be whether there is a universal structure to this phenotype bias that holds more widely and whether it also has such a clear effect on evolutionary outcomes in other biological systems.

If it is indeed the case that strong simplicity bias is common in nature, and if, as also suggested in (Johnston et al. 2021), the arrival of the frequent mechanism is important for the evolutionary dynamics of this much wider set of systems, then the conclusions for evolutionary causation driven by strong phenotype bias we draw here for RNA should hold much more widely in nature.