The Lie of Totally Neutral Mutations


Is eye colour a neutral mutation?
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An Example of a Neutral Mutation?

It is common belief that almost all mutations are neutral — they are neither harmful nor beneficial. As an example of such a mutation, one could say that a change in eye colour is neutral. After all, it has no noticeable harmful or beneficial effect.

But the idea of neutral mutations arises from a misunderstanding of genetics. Sure, a change in eye colour does not have a harmful or beneficial effect on the overall fitness of the animal (phenotype), but it does have an effect on the genetic content (genotype).

In other words, changing eye colour does not make the organism better or worse able to survive, but it does have a tiny effect on the actual genome and its processes. In much the same way, a single rust spot does not make the car less or better able to function, but it is slightly harmful to the car’s metal itself.

So how do we come to the conclusion that seemingly neutral mutations have an effect on the animal’s ‘building instructions’ (more specifically, the genotype)? Why is it that there is no such thing as a neutral mutation?

Nucleotides Cannot Be Neutral By Existence

By its very existence, a nucleotide cannot be neutral. This is because nucleotides take up space, affect spacing between other nucleotide sites, affect regional nucleotide composition, DNA folding, and nucleosome building.[1]

In fact, even if a nucleotide contains absolutely no information, it is still not neutral as it slows cell replication and wastes energy.[2]

Just like individual rust spots harm the metal of a car (but not the performance), nucleotides take up space, and affect other genetic factors (but do not affect the overall fitness of the organism). If given enough time, rust spots accumulate, eventually destroying the entire car. The same is true for mutations. If given enough time to build up, they will destroy the hosting organism. Now please take note that we are notsaying ‘mutations cannot be neutral to an animal’s overall appearance, or fitness’. Indeed, they often are. We are only saying that there is no such thing as a truly neutral mutation — one which affects absolutely nothing.

The Implications

So what’s the big deal? Who cares if mutations can never be completely neutral? Who cares if one organism dies off thanks to miniscule mutations?
Actually, these tiny mutations (we will call them “near neutral mutations” because they are not truly neutral) threaten the entire population — not just one individual! Here’s why:

An animal that has a harmful near-neutral mutation will not die out because the mutation is not big enough to be ‘noticeable’. The animal lives on to reproduce — with its offspring also acquiring that mutation (if it affected the reproductive cells). But now, those offspring not only have the mutation it got from its parents, but 100-300 entirely new near-neutral mutations.[3] By stark contrast, the famous geneticist, H.J. Muller, told us many years ago that a rate of only 0.5 mutations per person per generation would doom the human race![4]

The near-neutral mutations will spread throughout the entire population, and when enough time has elapsed, they will have accumulated to the point where the whole population dies out.
One thing is for sure: it becomes ‘beggars belief’ to think that humanity could last for hundreds of thousands of years without becoming extinct.


So, we have learnt that, by its existence, a nucleotide position cannot be neutral. This means that there is no way to mutate or change an individual without a biological effect. Ultimately, the entire population will become extinct because essentially all near neutrals are harmful.[5] And there are no truly neutral mutations to stop this genetic meltdown.

Possible Responses

  1. “Non-coding DNA absorbs mutations, making them neutral.”
    Non-coding DNA does not code for proteins and scientists have previously thought it is largely useless. But this idea is illogical for two reasons.
    Reason 1: it is wrong since non-coding DNA helps during embryonic development and can be a part of many diseases. Reason 2: just because scientists cannot see any function in non-coding DNA (in fact, we now know there is function and effects), that does not mean there is no function!
    The idea that non-coding DNA absorbs mutations making them neutral is plausibly false.
  2. “The proper definition for neutral in genetics is ‘a mutation which has no effect on the organism’s physical fitness (phenotype)’. You can’t even get that right.”
    This article is referring to truly neutral mutations (that which has absolutely no effect) as opposed to the typical definition of neutral mutations. Many lay evolutionists confuse the two and say that neutral mutations are truly neutral – hence the need for this article.
  3. “Some codons code for the same amino acid. Therefore, a change from one to the other will not produce any change — even to the genotype.”
    This is a convincing response, but it too fails. Since certain codons (genetic ‘words’ composed of 3 nucleotides or ‘letters’) are less-used than others, the body does not produce as much tRNA for that specific codon[6]. Therefore, protein synthesis can be slowed. So even a seeming neutral change such as TCC to TCT (both of which produce the amino acid serine) is not completely neutral.


  1. Sanford, John C., Genetic Entropy and the Mystery of the Genome (New York: FMS Publications, 2005), 3rd edition, p. 21. Back to text
  2. Sanford, John C., Same as Reference 1. Back to text
  3. Kondrashov, A.S., “Direct Estimate of Human Per Nucleotide Mutation Rates at 20 Loci Causing Mendelian Diseases,” Human Mutation 21:12-27, 2002; Nachman, M.W., Crowell, S.L., “Estimation of the Mutation Rate Per Nucleotide in Humans,” Genetics 156:297-304, 2000; Sanford, John C., Genetic Entropy and the Mystery of the Genome (New York: FMS Publications, 2005), third edition, p. 21. Back to text
  4. Muller. H.J., “Our Load of Mutations,” American Journal of Human Genetics 2: 111-176.Back to text
  5. Sanford, John C., Genetic Entropy and the Mystery of the Genome (New York: FMS Publications, 2005), third edition. See also, Gerrish, P.J., Lenski. R., “The fate of Competing Beneficial Mutations in an Asexual Population,” Genetica 102/103: 127-144, 1998. Back to text
  6. D. Clark and L. Russell, Biochemistry (Cache River Press, Vienna, IL), 1999, p. 220. Back to text
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