30 years of Natural Selection calculations (Ka/Ks) down the drain


The Ka/Ks ratio is a measure of the ratio of nonsynonymous (amino acid changing) mutations to synonymous (silent) mutations in two DNA sequences. It has been used for over 30 years in over 10,000 research articles to estimate the strength of natural selection on a gene or protein. However, it has been shown that the Ka/Ks ratio is inaccurate due to non-neutral synonymous mutations.

Non-neutral synonymous mutations are synonymous mutations that have a functional (fitness) effect. This can happen if the mutation changes the expression of the gene, the stability of the protein, or the interaction of the protein with other proteins. These mutations can influence the fitness of the organism even though they do not change the amino acid sequence of the protein. NeoDarwinism assumes that if no change occurs in the amino acid sequence (Ks) then no change in natural selection. This proves neodarwinian assumptions were clearly wrong.

As a result, the Ka/Ks ratio overestimates the strength of natural selection on a gene or protein if it does not take into account non-neutral synonymous mutations.

Synonymous mutations are mutations in the DNA sequence of a gene that do not change the amino acid sequence of the protein that the gene encodes. These mutations are often assumed to be neutral, per NeoDarwinism meaning that they have no effect on the fitness of the organism. However, recent studies have shown that a significant proportion of synonymous mutations are actually non-neutral, meaning that they can have either beneficial or harmful effects on fitness disproving NeoDarwinism.

There are a number of reasons why synonymous mutations might be non-neutral. One possibility is that they can affect the expression of the gene, either by changing the level of mRNA production or by altering the stability of the mRNA. Another possibility is that they can affect the folding of the protein, which can lead to changes in its function.

The finding that a significant proportion of synonymous mutations are non-neutral has important implications for our understanding of evolution. It proves that calculations of natural selection (Ka/Ks) are inaccurate per NeoDarwinism.

Here are some of the potential consequences of non-neutral synonymous mutations:

  • They affect the way scientists calculate natural selection using the Ka/Ks ratio. These calculations are on average 40% to high making over 10,000 articles incorrect in predicting natural selection.

  • They can lead to changes in the expression of genes, which can have a variety of effects on the organism's phenotype.

  • They can alter the folding of proteins, which can lead to changes in their function.

  • They can affect the stability of mRNA, which can reduce the amount of protein that is produced.

  • They can interact with other mutations to produce a cumulative effect.

The study of non-neutral synonymous mutations is a growing field of research, and it discounts NeoDarwinian effects on evolution.


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