Neutral Theory of Evolution Debunked

Elaborating on Michael Behe’s refutation of “neutral evolution”

by Jerry Bergman, PhD

Introduction

Michael Behe’s new book Darwin Devolves is already number one in new releases on Amazon.[1] To adequately summarize it would take a small book, so I will look at one small section where he reviews the attempts to salvage Darwinism, which he shows always fail. I have also added a few references to support Behe’s conclusions.

The main problem in evolution, as stated by the late Harvard Biology Professor William E. Castle, is the origin “of a new organism is one of the least understood of all natural phenomena. Even to the trained biologist it is an unexplained mystery.”[2] This statement is still true over a century later. One attempt to explain the origin of new organisms is the neutral theory of evolution. Neutral theory, along with genetic drift, natural selection and random mutation, is viewed by its supporters to be a basic mechanism of macroevolution.[3]

The Neutral Theory of Evolution

A neutral mutation is one that does not adversely affect either an organism’s phenotype nor its fitness.[4] The neutral theory of evolution postulates the accumulation of neutral mutations, such as accidental duplication of a section of DNA that causes no harm. This occurs until a new combination produces a DNA set that, in the future, confers some specific survival advantage to the organism.[5]

The theory accepts the view that about one percent of the human DNA codes for proteins, and significant portions of the rest is evidence of, or could be due to, neutral mutations.[6] Later,

other lucky mutations could occur in the extra DNA to confer some helpful feature, perhaps a regulatory site. Repeat this scenario many times over, and small populations of bacteria could evolve larger and larger genomes with more and more sophisticated features.[7]

The theory proposes that, when environmental conditions change, some of these neutral mutations may have produced a new gene, or a set of bases, that turns out to be beneficial in the new environment.[8] Neutral evolution theory has earned the qualified support of many leading evolutionary scientists, including Arizona State University Professor Michael Lynch, Eugene Koonin of the National Center for Biotechnology, and the late Harvard Professor Steven Jay Gould.[9]

University of Chicago evolutionist Jerry Coyne wrote, the two main neo-Darwinian evolutionary mechanisms are natural selection and the genetic variety produced by genetic drift.[10] The theory is anti-neo-Darwinian as explained by one of the early leaders of the idea, Motoo Kimura, who wrote that in

sharp contrast to the Darwinian theory of evolution by natural selection, the neutral theory claims that the overwhelming majority of evolutionary changes at the molecular level are caused by random fixation (due to random sampling drift in finite populations) of selectively neutral (i.e., selectively equivalent) mutants under continued inputs of mutations.[11]

Neo-Darwinism postulates that evolution works by fine-tuning genes that give a slight survival advantage to the population so that it gradually gives the organism a progressively greater survival advantage. Evolution is not the active agent in this scenario. It is a result, not an action. The neutral theory of evolution holds that most evolutionary changes are random, and most of the variation within, and between, species is ultimately not caused by natural selection, but by random genetic drift of neutral alleles originally produced by mutations. Kimura adds that neutral theory

also asserts that most of the genetic variability within species at the molecular level (such as protein and DNA polymorphism) are selectively neutral or very nearly neutral and that they are maintained in the species by the balance between mutational input and random extinction.[12]

He concludes that “since the origin of life on Earth, neutral evolutionary changes have predominated over Darwinian evolutionary changes” (1991, p. 367).

Genetic Drift

The basis of neutral theory is genetic drift, which postulates that genomic DNA base pairs change primarily by random genetic mutations and other genetic events. Genetic drift (or allelic drift) is a change in the frequency of a gene variant (allele) in a population that does not confer an immediate selection advantage to the organism. If this event occurs in gametes, the end result is the creation of new genetic variety that may, in the future, be evolutionarily advantageous. Drift can also occur in selective alleles, and can also have a selective disadvantage.

A major reason neutral theory was proposed is because “all the central assumptions of the Modern Synthesis (often called Neo-Darwinism) have been disproved.”[13] The late geneticist Dr. Motoo Kimura proposed neutral theory in 1968 because many molecular research findings were “quite incompatible with the expectations of Neo-Darwinism.”[14] A major problem was that evolution from one gene family type to another different family type, has never been directly documented. Furthermore, intermediate gene forms between the old, less-functional or non-functional and new, more-functional, gene by random mutations as proposed by Darwinism, is seriously problematic.

Thus, neutral theory “is in sharp contrast to the traditional neo-Darwinian (i.e., the synthetic) theory of evolution, which claims that the spreading of mutants within the species in the course of evolution can occur only with the help of positive natural selection.”[15] Neutral theory also, in contrast to Darwinism, postulates that, if selection occurs, the genes selected in the next generation are more likely to be those genes from a “lucky” few individuals, and not necessarily from those life-forms that are healthier or in some way “better.”

Neutral theory supporters accept the conclusion that most mutations are slightly deleterious, but claim that, because these mutant genes are rapidly purged by natural selection, they do not make significant contributions to the variation within and between species at the molecular level. They claim that only neutral mutations, or those that are close-to-neutral, can achieve this.

In contrast to the neutral theory, much evidence now exists for the view that most mutations are not strictly neutral, but near-neutral, meaning not harmful as a single entity, but collectively accumulate, eventually causing disease or death. Aging is the most well-documented example of the accumulation of near-neutral mutations. As all animals age and die, so too does a species by the same mechanism, the accumulation of near-neutral mutations.

The Junk and Duplicated DNA Problem

A major difficulty with neutral theory is the assumption that most or at least much DNA is selectively neutral based on the belief that most DNA is non-functional. As Kimura concluded, neutral theory “asserts that most intraspecific variability … is selectively neutral.”[16] Junk DNA was assumed to be a major source of raw, genetic material that can gradually be modified by genetic drift or mutations to change into a gene that eventually becomes functional. However, the ENCODE project has documented that over 80 percent of all so-called junk DNA is actually functional,[17] thus creating a major problem for neutral theory.

Biology Professor Nathan Lents admits, even if only one mutation renders a gene broken, repair “is like a lightning strike… The odds of lightning striking the same place twice are so infinitesimally tiny as to be nonexistent…. it’s exceeding unlikely that a mutation will fix a broken gene because, following the initial damage, the gene will soon rack up additional mutations.”[18]  He adds, if over half of our genes are broken, how can we survive as a species?

His answer is “the majority of these pseudogenes are the result of accidental gene duplications [which] .. . explains why the disrupting mutations and subsequent death of the gene didn’t have any deleterious effects on the individual.”  This is the common explanation for why most mutations do not appear to adversely affect the genome, a view that was falsified by the ENCODE findings. If one specific base change is very unlikely, the probability of massive changes that result in a new gene that proves beneficial in the future is far less likely.

Another hypothesized source of new genes is gene duplication, enabling one gene to continue to carry out the function that it was originally evolved to fulfill, and the other gene to evolve into a new gene that can serve another, new function in the genome.[19] The problems with this view have been well documented.[20] One problem with the duplication theory is that both genes are generally equally susceptible to new mutations, likely damaging both the original and the new gene.

Another problem is, if one gene is duplicated and mutations occur in the original, or the copied gene, it will not be selected until, and unless, the new protein the gene produces is functional and confers some selective advantage to the organism. Until then, if it produces a protein, the protein will often be cut up and the parts recycled. The evolution from junk DNA theory faces the same problem. To solve these problems was one reason why the neutral theory was originally proposed.

The major problem with the neutral theory is the fact that a non-functional gene is not just useless, but worse. If it does not serve some beneficial function in the organism it could adversely affect the organism. The high cost of duplicating and maintaining the gene is one reason why nonfunctional genes are costly for the cell.

Another problem is mutations are not always random. Most occur in hot spots and tend to degenerate into certain bases, such as thymine, and also into a code for certain amino acids, namely those produced by six different sets of bases such as Serine, which is coded for by TCT, TCC, TCA, TCG, ATG, AGC). Both Arginine, and Leucine are also coded for by six combinations of base pairs. The result is random combinations will code for these amino acids 9.4 percent of the time and those produced by one different base set, such as Tryptophan (coded for by TGG) and Methionine (coded for by ATG) will be produced by chance only 1.6 percent of the time.

Gene Regulation

To be functional, a gene requires the proper transcription factors and other regulation and control systems. A gene that has evolved by neutral theory, even if it could produce a useful product, is useless until it has the proper regularity and control mechanisms, including the spliceosome system required to remove introns. Control of both up- and down-regulation of all genes is also critical for cell and organism survival.

This is illustrated by the transposition of a gene somewhere else in the genome, such next to a gene that, as a result, is improperly regulated. An example is a housekeeping gene that is transposed to a gene which causes up-regulation of cell division.[21] Also, transposition of a gene next to a regulatory sequence that is constitutively expressed can also cause that gene to be over-expressed, resulting in cancer or other problems.[22]

DNA Repair

The DNA repair systems also work against genetic drift. It is now well-documented that “DNA is an alarmingly fragile molecule…. vulnerable to UV light and mutagenic chemicals, as well as spontaneous decay. Life has survived through the ages because enzymes inside every cell ensure that DNA remains in proper working order.”[23] Critical to this survival are the dozen or so DNA repair mechanisms that resist genetic drift, thus working against neutral evolution theory.

The mechanism that repairs DNA to ensure that the molecule is very stable repairs most genetic-drift changes in spite of the fact that without this repair system “under normal conditions, DNA quickly suffers enough damage to make life impossible.”[24]

The DNA repair system is highly effective except in cells that have accumulated a large amount of DNA damage, such as cancer cells. Cancer is often due to mutations of key parts of the repair system, such as p53, the so-called “guardian of the genome.” Cells that can no longer effectively repair DNA damage enter one of three possible states: 1) an irreversible state of dormancy known as senescence, 2) cell suicide known as apoptosis or programmed cell death, or 3) unregulated cell division, which can lead to a cancerous tumor. None of these conditions permits the genetic drift that allows for neutral evolution.

The Molecular Clock Problem

The main factors that motivated the neutral theory proposal include two observations that created problems for Neo-Darwinism. One was the so-called evolutionary genetic clock that was based on base substitutions of amino acids that resulted from DNA changes.[25] Functioning of this clock requires a fairly consistent rate of change in most organisms.

In large populations, if mutation rates are roughly the same for most genes, then simple, random models will predict a molecular clock.[26] Because both of these considerations are erroneous, the molecular clock is not consistent. The major problem is that the genetic clock

makes no sense in Darwin’s world, where molecules subject to strong selection should evolve faster than others, and where organisms exposed to different changes and challenges from the environment should vary their evolutionary rates accordingly.[27]

Gould acknowledged that the “molecular clock is neither as consistent nor as regular as Kimura once hoped.”[28]

The refutation of the molecular clock was only one of several major blows to neutral theory.[29] Kimura referred to the discovery that high levels of variation are maintained by many genes in the population. The problem for neutral theory was too much variation in genetic changes

poses a problem for conventional Darwinism because a cost can be associated with the replacement of an ancestral gene by a new and more advantageous state of the same gene—namely, the differential death, by natural selection, of the new disfavored parental forms. This cost poses no problem if only a few old genes are being pushed out of a population at any time.[30]

Furthermore, “if hundreds of genes are being eliminated” by natural selection because they are deleterious, then any one organism likely possesses many of the deleterious mutant genes, impairing its survival chances. Consequently,

the data on copious variability seemed to indicate a caldron of evolutionary activity at far too many genetic sites—too many, that is, if selection governs the changes in each varying gene. Kimura, however, recognized a simple and elegant way out of this paradox. If most of the varying forms of a gene are neutral with respect to selection, then they are drifting in frequency by the luck of the draw, invisible to natural selection because they make no difference to the organism.[31]

Today, the term neutral theory is often defined narrowly in terms of the result of sampling disparities, although this narrow definition is problematic.

Neutral Theory Conflicts with Darwinism

Kimura’s  conception of neutral theory obviously posed serious problems for Darwinism. To avoid the problem of directly challenging Darwinism, which could produce enormous opposition to his theory, Kimura does not openly deny it, but rather views the Darwinian “processes as quantitatively insignificant to the total picture—a superficial and minor ripple upon the ocean of neutral molecular change, imposed every now and again when selection casts a stone upon the waters of evolution.”[32] Conversely, orthodox Darwinians, “tended to argue that neutral change occupied a tiny and insignificant corner of evolution—an odd process occasionally operating in small populations at the brink of extinction anyway.”[33]

Conclusions

A major evolutionary problem that neutral theory attempts to address is, ever since

Darwin proposed his theory of natural selection to explain evolution, most evolutionary theories have always been a matter of debate and controversy. The neutral theory was not an exception.[34]

Genetics research has progressed well beyond that in Kimura’s day, refuting neutral theory. Furthermore, because “the neutral theory is quantitative, it is able to make testable predictions.”[35] As the late Cornell Professor William Provine and others have documented, the testable predictions for neutral theory, especially random drift, have largely failed.[36] The evidence against neutral theory is now overwhelming, and as a result the theory has been regulated to the  dustpan of history. As Alvarez-Valin noted, the predictions of neutral theory flatly do not agree with many of the scientific facts.[37]

References

[1] Behe, Michael. 2019. Darwin Devolves: New Science About DNA that Challenges Evolution. New York, NY: HarperOne.

[2]Castle, William E.. 1916. Genetics and Eugenics. A Textbook for Students of Biology. Cambridge, MA: Harvard University Press, p. 4.

[3] Tomkins, Jeffrey and Jerry Bergman. 2017. Neutral model, genetic drift and the third way—A synopsis of the self-inflicted demise of the evolutionary paradigm. Journal of Creation. 31(3):94–102

[4]Duret, Laurent. 2008. Neutral theory: The null hypothesis of molecular evolution. Nature Education. 1(1):218.

[5] Alvarez-Valin, F. 2002. Neutral theory. Encyclopedia of Evolution. New York, NY: Oxford University Press, pp. 815–821; Behe, 2019, p. 99.

[6] Behe, 2019, pp. 98-99.

[7] Behe, 2019, p. 100.

[8] Kimura, M. 1979. “The Neutral Theory of Molecular Evolution.” Scientific American. November, 241:98-129.

[9] Behe, 2019, p. 104.

[10] Coyne, Jerry. 2015. Faith vs Fact: Why Science and Religion Are Incompatible. New York, NY: Viking, pp. 139–140..

[11]Kimura, M. 1991. Recent development of the neutral theory viewed from the Wrightian tradition of theoretical population genetics. Proceedings of the National Academy of Science. 88:5969–5973, p. 367. Kimura, M. 1991. The neutral theory of molecular evolution: a review of recent evidence. Japanese Journal of Genetics. 6(4):367-386.

[12] Kimura, 1991, p. 367.

[13]Noble, D. 2013. Physiology is rocking the foundations of evolutionary biology. Experimental Physiology. 98(8):1235–1243, p. 1235.

[14]Kimura, M. 1983. The Neutral Theory of Molecular Evolution. New York, NY: Cambridge, p. 25.

[15] Kimura, 1991, p. 5969.

[16] Kimura, 1991, p. 5969.

[17] Luskin, C. (2012, September 5) “Junk No More: ENCODE Project Nature Paper Finds ’Biochemical Functions for 80% of the Genome’.” Evolution News. Retrieved June 7, 2018 from https://evolutionnews.org/2012/09/junk_no_more_en_1/

[18] Lents, Nathan. 2018. Human Errors. Boston, MA: Houghton Mifflin. p. 72.

[19] Behe, 2019, p. 99.

[20] Bergman, Jerry. 2006. Does gene duplication provide the engine for evolution? Journal of Creation. 20(1):99–104

[21]Prelich, G. 2012. Gene overexpression: Uses, mechanisms, and interpretation. Genetics. 190:841–854.  Retrieved June 7, 2018 from http://www.genetics.org/content/genetics/190/3/841.full.pdf.

[22] http://www.genetics.org/content/190/3/841.full.pdf+html.

[23]Stokstad, E. 2015. DNA’s repair tricks win chemistry’s top prize.[not a subtitle; only the website’s tease for the article] Science. 350(6258):266, p. 266.

[24] Stokstad, 2015, p. 266.

[25] Kimura, M. 1987. Molecular evolutionary clock and the neutral theory. Journal of Molecular Evolution. 26:24–33. Kimura, M. 1968. Evolutionary rate at the molecular level. Nature. 217:624–626.

[26]Gould, S.J. 1989. Through a lens darkly. Natural History. September, pp. 16–24, p. 17.

[27] Gould, 1989, p. 17.

[28] Gould, 1989, p. 17.

[29] Tomkins, Jeffrey and Jerry Bergman. 2015. Evolutionary molecular genetic clocks—A perpetual exercise in futility and failure. Journal of Creation. 29(2):26–35.

[30] Gould, 1989, p. 17.

[31] Gould, 1989, p. 17.

[32] Gould, 1989, p. 17.

[33] Gould, 1989, p. 17.

[34] Alvarez-Valin. 2002, p. 821.

[35] Alvarez-Valin. 2002, p. 821.

[36] Provine, William B. 2014. The “Random Genetic Drift” Fallacy. Published by Author.

[37] Alvarez-Valin, 2002, p. 821; Wolf, J.B., E.D. Brodie, III, and M.J. Wade, eds. 2000. Epistasis and the Evolutionary Process. New York, NY: Oxford University Press.

---

Dr. Jerry Bergman has taught biology, genetics, chemistry, biochemistry, anthropology, geology, and microbiology at several colleges and universities including for over 40 years at 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.