"Non Neutral" Synonymous mutations challenge 60 years of NeoDarwinism

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The Nature Journal article, "Synonymous Mutations in Representative Yeast Genes Are Mostly Strongly Non-neutral" by Shen et al. (2022) challenges NeoDarwinism in many ways.

Neo Darwinism is the prevailing theory of evolution, which states that evolution is driven by natural selection of random mutations. Natural selection works by favoring mutations that make an organism more fit to its environment, and eliminating mutations that make an organism less fit.

Synonymous mutations are a type of mutation that does not change the amino acid sequence of the protein that is encoded by a gene. Since synonymous mutations do not change the protein sequence, for 60 years they were thought to be neutral per NeoDarwinism, meaning that they have no effect on the fitness of an organism. This was in part to the non curious acceptance of the genetic code as a "frozen accident" by DNAs Francis Crick. He simply applied NeoDarwinism post hoc to explain synonymous codons rather than asking why they were this way.

However, this study challenges this long-held assumption. The study found that most synonymous mutations are actually strongly non-neutral, meaning that they have a significant effect on the fitness of an organism.

The Study

The study was conducted by a team of researchers from the University of California, Berkeley. The researchers used a technique called deep barcoded sequencing to measure the fitness effects of thousands of synonymous mutations in 21 representative yeast genes. This is a new technique using the Nobel work of the Cas9 Crispr genetic engineering method to generate precise mutation maps to measure ACTUAL "fitness" as opposed to derived natural selection effects based on pos hoc equations relying on the now defunct neutrality of synonymous mutations.

The researchers found that three-quarters of the synonymous mutations resulted in a significant reduction in fitness. The distribution of fitness effects was overall similar between synonymous and nonsynonymous mutations, which are mutations that do change the amino acid sequence of the protein. Again this is huge as for 60 years natural selection was claimed "mathematically" by comparing synonymous and nonsynonymous mutations in overly simplified equations like the Ka/Ks ratios.


Note how neodarwinists claimed purifying (negative), neutral and positive (Darwin's Natural selection) based on an overly simplified model which was based on flawed NeoDarwinian assumptions. The researchers also found that synonymous mutations frequently disturbed the level of mRNA expression of the mutated gene. The extent of the disturbance partially predicted the fitness effect of the mutation.

Implications for Neo Darwinism

The findings of this study have important implications for neo darwinism. If most synonymous mutations are strongly non-neutral, then it means that there is much less neutral variation in the genome than previously thought. This would have a significant impact on our understanding of how evolution works.

For example, if there is less neutral variation in the genome, then it means that  populations are more likely to be stuck in local optima, which are evolutionary traps that can prevent populations from evolving.

The findings of this study also challenge the assumption that synonymous mutations can be used to estimate neutral mutation rates. If synonymous mutations are not neutral, then they cannot be used to accurately estimate the rate at which mutations occur in the genome. Over 30,000 journal articles over recent decades "measured" natural selection based on numbers of synonymous mutations eg Ka/Ks above.

Conclusion

The study by Shen and colleagues is a significant challenge to the prevailing theory of evolution. The findings of the study suggest that most synonymous mutations are strongly non-neutral, which would have a major impact on our understanding of how evolution works.

The study also highlights the importance of further research on synonymous mutations. Synonymous mutations have traditionally been ignored because they were thought to be neutral. However, the findings of this study suggest that synonymous mutations may play an important role in evolution.

Additional Thoughts on the Implications for Neo Darwinism

In addition to the implications mentioned above, the findings of this study also challenge the following tenets of neo darwinism:

  • The assumption that evolution is gradual. If most synonymous mutations are strongly non-neutral, then it means that evolution can occur much more rapidly than previously thought. This is because synonymous mutations can have a large impact on fitness without changing the amino acid sequence of the protein.

  • The assumption that evolution is adaptive. If synonymous mutations are strongly non-neutral, then it means that evolution can be driven by non-adaptive forces, such as genetic drift. This is because synonymous mutations can have a large impact on fitness even if they are not beneficial to the organism.

  • The assumption that evolution is predictable. If most synonymous mutations are strongly non-neutral, then it means that evolution is much more unpredictable than previously thought. This is because the fitness effects of synonymous mutations are difficult to predict.

Overall, the findings of this study have the potential to revolutionize our understanding of evolution. The study challenges many of the fundamental assumptions of neo darwinism and suggests that evolution is much more complex than previously thought.

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