A wikipedia of Dr. D'Adamo's research


See Also

  • [ABO and Secretor Blood group Genetics]?
  • [Genetic drift]?
  • [Motoo Kimura]?
  • [Synonymous (silent) substitution]?


The neutral theory of molecular evolution (also, simply the neutral theory of evolution) is an influential theory that was introduced with provocative effect by [Motoo Kimura]? in the late 1960s and early 1970s. Although the theory was received by some as an argument against Darwin's theory of evolution by natural selection, Kimura and most evolutionary biologists today maintain that the two theories are compatible. The theory attributes a large role to genetic drift.


While some scientists had hinted that maybe neutral mutations were widespread, like Sueoka (1), a coherent theory of neutral evolution was first formalized by Motoo Kimura in 1968, followed quickly by King and Jukes provocative article, "Non-Darwinian Evolution" (2).

According to Kimura, when one compares the genomes of existing species, the vast majority of molecular differences are selectively "neutral." That is, these differences do not influence the fitness of either the species or the individuals who make up the species. As a result, the theory regards these genome features as neither subject to, nor explicable by, natural selection. This view is based in part on the genetic code, according to which sequences of three nucleotides (codons) may differ and yet encode the same amino acid (GCC and GCA both encode alanine, for example). Consequently, many potential single-nucleotide changes are in effect "silent" or "unexpressed" (synonymous or silent substitution). Such changes are presumed to have little or no biological effect. However, it should be noted that the original theory was based on the consistency in rates of amino acid changes, and hypothesized that the majority of those changes too were neutral.

A second assertion or hypothesis of the neutral theory is that most evolutionary change is the result of genetic drift acting on neutral alleles. A new allele arises typically through the spontaneous mutation of a single nucleotide within the sequence of a gene. In single-celled organisms, such an event immediately contributes a new allele to the population, and this allele is subject to drift. In sexually reproducing, multicellular organisms, the nucleotide substitution must arise within one of the many sex cells that an individual carries. Then only if that sex cell participates in the genesis of an embryo and offspring does the mutation contribute a new allele to the population. Neutral substitutions create new neutral alleles.

Through drift, these new alleles may become more common within the population. They may subsequently decline and disappear, or in rare cases they may become "fixed"--meaning that the substitution they carry becomes a universal feature of the population or species. When an allele carrying one of these new substitutions becomes fixed, the effect is to add a substitution to the sequence of the previously fixed allele. In this way, neutral substitutions tend to accumulate, and genomes tend to evolve.

According to the mathematics of drift, when looking between two species or two isolated populations, most of their single-nucleotide differences can be assumed to have accumulated at the same rate as individuals with mutations are born. This latter rate, it has been argued, is predictable from the error rate of the enzymes that carry out DNA replication--enzymes that have been well studied and are highly conserved across all species. Thus, the neutral theory is the foundation of the molecular clock technique, which evolutionary molecular biologists use to measure how much time has passed since species diverged from a common ancestor. While the mutation rate is no longer considered a constant, diverse and more sophisticated clock techniques have emerged.

Many molecular biologists and population geneticists, besides Kimura, contributed to the development of the neutral theory, which may be viewed as an offshoot of the modern evolutionary synthesis.

The "neutralist-selectionist" debate

A heated debate arose on the initial publication of Kimura's theory, in which discussion largely revolved around the relative percentages of alleles that are "neutral" versus "non-neutral" in any given genome. Contrary to the perception of many onlookers, the debate was not about whether or not natural selection acts at all.

After flirting with the idea that slightly deleterious mutations might be quite common (3), Tomoko Ohta, Kimura's student, made an important generalisation of the neutral theory by including the concept of "near-neutrality" (4,5), that is, genes that are affected mostly by drift or mostly by selection depending on the effective size of a breeding population. The neutralist-selectionist quarrel has since cooled, yet the question of the relative percentages of neutral and non-neutral alleles remains. Graur & Li (6), go as far as to say; "There are only two predictions we are willing to make about the future of molecular evolution. The first concerns old controversies. Issues such as the neutralist-selectionist controversy or the antiquity of introns, will continue to be debated with varying degrees of ferocity, and roars of "The Neutral Theory Is Dead" and "Long Live the Neutral Theory" will continue to reverberate, sometimes in the title of a single article."

As of the early 2000s, the neutral theory is widely used as a "null model" for so-called null hypothesis testing. Researchers typically apply such a test when they already have an estimate of the amount of time that has passed since two species or lineages diverged--for example, from radiocarbon dating at fossil excavation sites, or from historical records in the case of human families. The test compares the actual number of differences between two sequences and the number that the neutral theory predicts given the independently estimated divergence time. If the actual number of differences is much less than the prediction, the null hypothesis has failed, and researchers may reasonably assume that selection has acted on the sequences in question. Thus such tests contribute to the ongoing investigation into the extent to which molecular evolution is neutral.

Significance with regard to ABO blood groups

From Matt Ridley's Genome: A History of a species in 23 Chapters:

"But this is where things get interesting. If blood groups are invisible and neutral, then how did they evolve to the present state? Was it pure chance that landed the inhabitants of the Americas with type 0 blood? At first glance the blood groups seem to be an example of the neutral theory of evolution, promulgated by Motoo Kimura in 1968: the notion that most genetic diversity is there because it makes no difference, not because it has been picked by natural selection for a purpose. Kimura's theory was that mutation pumps a continual stream of mutations that do not affect anything into the gene pool, and that they are gradually purged again by genetic drift – random change. So there is constant turnover without adaptive significance. Return to earth in a million years and large chunks of the human genome would read differently for entirely neutral reasons.

`Neutralists' and `selectionists' for a while grew quite exercised about their respective beliefs, and when the dust settled Kimura was left with a respectable following. Much variation does indeed seem to be neutral in its effects. In particular, the closer scientists look at how proteins change, the more they conclude that most changes do not affect the 'active site' where the protein does its chemical tricks. In one protein, there have been 250 genetic changes since the Cambrian age between one group of creatures and another, yet only six of them matter at all." (7)


1. Sueoka, N. (1962). "On the genetic basis of variation and heterogeneity of DNA base composition". PNAS USA 48: 582–592.

2. King, J.L. and Jukes, T.H (1969). "Non-Darwinian Evolution". Science 164: 788-798.

3. Ohta, T (1973). "Slightly deleterious mutant substitutions in evolution". Nature 246: 96-98.

4. Ohta, T (1992). "The nearly neutral theory of molecular evolution". Annual Review of Ecology and Systematics 23: 263-286.

5. Ohta, T. (2002). "Near-neutrality in evolution of genes and gene regulation". Proceedings of the National Academy of Sciences 99: 16134-16137.

6. Graur, D. and Li, W-H (2000). Fundamentals of Molecular Evolution, 2nd edition. Sinauer Associates.

7. Ridley, M. A History of a a species in 23 Chapters. Harper Perennial, New York. 2006



The Complete Blood Type Encyclopedia is the essential desk reference for Dr. D'Adamo's work. This is the first book to draw on the thousands of medical studies proving the connection between blood type and disease.

Click to learn more

Click the Play button to hear to Dr. Peter J. D'Adamo discuss .

The statements made on our websites have not been evaluated by the FDA (U.S. Food & Drug Administration).
Our products and services are not intended to diagnose, cure or prevent any disease. If a condition persists, please contact your physician.
Copyright © 2015-2023, Hoop-A-Joop, LLC, Inc. All Rights Reserved.     Log In