June 21, 2022 | Jerry Bergman

Mutations Are Not the Main Source of Genetic Variety for Evolution

New research study has created
more problems for neo-Darwinism


by Jerry Bergman, PhD

A new study out of the University of Michigan has presented another problem for Neo-Darwinism.

Neo-Darwinism is the belief that the existence of all life on Earth is due to genetic mutations, which produce genetic variety that is then culled by natural selection. This process, the theory concludes, causes evolution from lower life forms to higher, more advanced, life forms. In standard evolutionary theory, life is built on the back of mutations. Since the beginning days of neo-Darwinism in the 1930s, geneticists have come to the realization that the vast majority of mutations are harmful. Some are thought to be slightly harmful, others greatly so. Evolutionists have attempted to come to terms with this fact by adopting a common assumption that the vast majority of the genome is useless junk. Thus, they argue that these many harmful mutations have no adverse effect on life. Another response has been to assume that a great percentage of mutations are “neutral” or silent, with no effect on fitness.

A new research program printed in Nature this month has discovered that most ‘silent’ genetic mutations are harmful—not neutral as evolutionists have long believed. This finding has broad implications for evolutionary biology. The authors of the new study reviewed here, by Xukang Shen et al., hint in their conclusion that their findings may add another nail in the Darwinian coffin. They say that the

strong non-neutrality of most synonymous mutations, if it holds true for other genes and in other organisms, would require re-examination of numerous biological conclusions about mutation, selection, effective population size, divergence time and disease mechanisms that rely on the assumption that synonymous mutations are neutral.[1]

Nonsynonymous vs. synonymous mutations

Single-letter mutations called point mutations do not change the protein the gene produces because the new codon codes for the same amino acid. For example, if the triplet codon ACU is changed to ACA, the code still produces threonine, so no change in the amino acid  sequence results. If UGG is mutated, producing UGA, this change is called a nonsynonymous mutation. In that instance the codon for an amino acid is changed into a stop code, truncating the chain. When that happens, the likely result will be a non-functional protein that will be recycled.

Conversely, those mutations that do not alter the protein sequences have been called silent or synonymous mutations. They were long-considered neutral. The “strong non-neutrality of most synonymous mutations” that Xukang et al. discovered, if found to be the case for other genes and in other organisms, has major implications for evolutionary biology.[2]

Synonymous mutations have been long-ignored in the study of disease-causing mutations. But as Xukang et al. found, they might be a cause of (or contribute to) mutation-caused diseases such as cancer.[3] They would also play a role in contributing to the deterioration of the genome. The implications are profound. Mutations, rather than driving evolutionary progress from slime to humans, actually facilitate the degeneration of the genome, driving evolution downward into devolution.

Why would synonymous mutations cause problems if the same amino acid is inserted into the growing protein chain? The answer has to do with tRNA supply. The translation machinery is based on the number of specific codes. If ACU is changed to ACA the code still produces threonine but the number of transcription RNAs (tRNA) is matched to the ACU and ACA codons. If ACU is twice as common as ACA, the matching tRNA produced for ACU will be twice that produced for ACA.

The Xukang et al. finding means that genomes are deteriorating faster than thought. The study found between one-quarter and one-third of all point mutations in protein-coding DNA sequences are not silent as previously believed, but expressed.[4] The research study, furthermore, was not based on a few isolated cases. The team created 8,341 mutant yeast strains using the CRISPR/Cas9 technique. Each strain carried a synonymous, nonsynonymous, or nonsense mutation in one of 21 genes the scientists targeted.

The measure of fitness used

The researchers quantified the “fitness” of each mutant strain by measuring how rapidly it reproduced using the common assumption of Darwinian fitness: the higher the reproductive rate, measured by number of offspring, the higher the fitness.

The researchers concluded that fully 75.9% of synonymous mutations were significantly deleterious, and only 1.3% were significantly beneficial. There is no reason to believe these results are restricted to yeast, since mutations are common to all organisms. Confirmation studies with diverse organisms, though, will be necessary to verify the generality of their findings.

This paper overturns a long-believed assumption (based on ignorance of the genome’s functions) that most mutations do not cause eventual ‘mutation catastrophe.’  That assumption led Darwinians to claim that as much as 98 percent of the DNA was “junk” because those regions of the genome do not code for proteins. Because geneticists did not know the actual function of the 98% of non-coding regions, they assumed they had no function at all, thereby incorrectly assuming that non-coding regions of the genome are vestiges of evolution. Consequently, they assumed that mutations in non-coding regions did not cause damage to the functional parts (i.e., protein-producing parts) of the genome.[5]

Biologists now know that most of the genome once commonly considered “junk” is used for genetic regulation. Non-coding regions are transcribed into large numbers of micro-RNAs (miRNA), short interfering RNAs (siRNA), long noncoding RNAs (lncRNA) and other transcripts with a variety of functions, such as mutational sponges, scaffolding material, decoys and regulators.[6] The ENCODE project in 2012 reported evidence that 80 percent or more of the DNA once classified as “junk” has critical functions, mostly regulatory.

This means that the vast majority of mutations that were considered neutral because they occurred in the junk, i e., useless DNA, are actually harmful. The discovery that non-coding DNA has many critical functions means that many of these formerly neutral mutations do cause harm and contribute to the deterioration of the genome. A further implication of the Xukang et al. study is that most of the endogenous genes cannot tolerate mutations.

Consequently, most or even the majority, of mutations contribute to genetic deterioration, and thus genetic meltdown. This conclusion is lethal to progressive evolution. Mutations are not a seed plot for progress. Mutations cause devolution.

In the same issue of Nature, Nathan Sharp noted another problematic implication for evolutionary theory. Evolutionists have assumed that mutation rates can be used to infer when species diverged over time. That assumption is now cast into doubt:

[T]he number of synonymous differences between species is used as a ‘molecular clock’ to estimate how long ago speciation events took place — but these estimates would be inaccurate if selection actually constrains a lot of synonymous variation, effectively slowing the clock.[7]


If further research confirms the results of the Xukang study, it has enormous implications for evolution. One conclusion is all mutations are significant, not neutral. Thus, it is very likely that all mutations contribute to the deterioration of the genome. Simultaneously, the study reveals that the complexity of the genome is greatly increased, as is the requirement to possess a much more specific genomic code. The old, ignorant view allowed for more sloppiness. Alas, it appears those days are gone!


[1] Xukang Shen et al., Synonymous mutations in representative yeast genes are mostly strongly non-neutral Nature 361; https://www.nature.com/articles/s41586-022-04823-w, 8 June 2022. Bold added.

[2] Erickson, Jim. University of Michigan. Michigan News Study: Most ‘silent’ genetic mutations are harmful, not neutral, a finding with broad implications; https://news.umich.edu/study-most-silent-genetic-mutations-are-harmful-not-neutral-a-finding-with-broad-implications/, 8 June 2022.

[3] Erickson, 2022.

[4] Erickson, 2022.

[5] Bai, Nina, and Dana Smith. The Mysterious 98%: Scientists Look to Shine Light on Our Dark Genome. UCSF (University of California, San Francisco); https://www.ucsf.edu/news/2017/02/405686/mysterious-98-scientists-look-shine-light-our-dark-genome, 2 February 2017.

[6] Makalowski, Wojciech. Perspectives genomics: Not junk after all. Science 300(5623):1246–1247, 23 May 2003; Kondrashov, Alexey S. Evolutionary biology: Fruit fly genome is not junk. Nature 437(7062):1106a, 20 October 2005.

[7] Sharp, Nathan. Mutations matter even if proteins stay the same. Nature, doi: 10.1038/d41586-022-01091-6, 8 June 2022.

Dr. Jerry Bergman has taught biology, genetics, chemistry, biochemistry, anthropology, geology, and microbiology for over 40 years at several colleges and universities including Bowling Green State University, Medical College of Ohio where he was a research associate in experimental pathology, and The University of Toledo. He is a graduate of the Medical College of Ohio, Wayne State University in Detroit, the University of Toledo, and Bowling Green State University. He has over 1,300 publications in 12 languages and 40 books and monographs. His books and textbooks that include chapters that he authored are in over 1,500 college libraries in 27 countries. So far over 80,000 copies of the 40 books and monographs that he has authored or co-authored are in print. For more articles by Dr Bergman, see his Author Profile.

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  • tjguy says:

    It’s nice to see that the data supports the creationist position and challenges the Darwinian hypothesis.

    “Mutations, rather than driving evolutionary progress from slime to humans, actually facilitate the degeneration of the genome, driving evolution downward into devolution.”

    Creationists have been saying this for over a hundred years!

    I doubt it will change anything because evolution is unfalsifiable. They just keep tweaking it to accommodate whatever theory challenging data they encounter, but at least, it’s getting harder and harder to keep the faith. And things long assumed to be true by evolutionists are proving to be false. Their theory is no longer a theory. It is a failing hypothesis.

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