Evolution calculations by Ka/Ks ratios are being challenged

The Ka/Ks ratio is affected by new views that synonymous mutations are not neutral. For 30 years thousands of papers used the ratio to imply Natural selection. This is changing but will scientists publish errata corrections? I think not.

The Ka/Ks ratio is a measure of the relative rates of nonsynonymous and synonymous substitutions in a gene or genome. Nonsynonymous substitutions are those that change the amino acid sequence of a protein, while synonymous substitutions are those that do not. Per NeoDarwinism nonsynonymous mutations causes evolution. A high Ka/Ks ratio suggests that the gene is under strong selective pressure, while a low Ka/Ks ratio suggests that the gene is under weak or no selective pressure.The Ka/Ks ratio till now was used to infer the evolutionary history of a gene or genome

Per NeoDarwinism, Synonymous mutations are those that do not change the amino acid sequence ergo don't change the phenotype for natural selection to act.

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A 2022 study found that synonymous mutations in representative yeast genes are mostly strongly non-neutral. This is completely different than NeoDarwinism. This means that they are not simply neutral changes that have no impact on the protein's function. Instead, they are more likely to be beneficial or deleterious. This finding has implications for the use of the Ka/Ks ratio to estimate the strength of selection on a gene. The Ka/Ks ratio is calculated as the ratio of nonsynonymous substitutions to synonymous substitutions. If synonymous mutations are not neutral, then the Ka/Ks ratio will underestimate the strength of selection on a gene.

The new view that synonymous mutations are not neutral has important implications for our understanding of evolution. It suggests "fitness" outside of natural selection on the DNA sequence itself. This represents a second code in the DNA.This could explain why some genes are more conserved than others. Genes that are under strong epigenetic changes are being used  are not changes in the amino acid sequence.

The new view of synonymous mutations is still under investigation. It is not yet clear how widespread this phenomenon is, or what the exact mechanisms are that are driving it. However, the finding that synonymous mutations are not neutral is a significant advance in our understanding of evolution which challenges 60 years of Neo-Darwinism.


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