Neutral theory of molecular evolution

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The neutral theory of molecular evolution (English neutral theory of molecular evolution ) is part of the evolution theory , it was founded in the late 1960s by Motoo Kimura . Their key message is that most genetic changes are neutral with regard to natural selection , so they do not offer the individual any direct advantages or disadvantages. It follows that random events such as genetic drift play a far greater role in the evolution of genetic information than changes that are driven by selection. The neutral theory of molecular evolution expressly does not exclude the importance of selection-driven changes for certain gene sequences. While these sequences can play a major role in the observable and therefore selectable phenotype , they only make up a small part of the genetic information.


The neutral theory was formulated by Motoo Kimura in the 1960s . By comparing the amino acid sequences of proteins in different species , he found that the rate of evolution of the amino acid sequences of some proteins is constant. This constancy cannot be explained by selection, but only by genetic drift. It was a counterbalance to the prevailing view at the time that every mutation was important for selection. However, it was expressly not an alternative to selection theory, but an extension.

The title of an article by JL King and TH Jukes, Non-Darwinian Evolution in Science (Volume 164, 1969, p. 788 ff.), However, led to a discussion as to whether the neutral theory and molecular biology generally question Darwinian-style evolutionary theory put. However, it soon became clear that this was not the case. However, they show that not all mutations are subject to selection (so-called silent mutations).

In the so-called neutralist-selectionist debate, the first issue was whether there are neutral mutations at all. This is widely recognized today. The extent of the proportion of neutral mutations is still being discussed.

Causes and occurrence of neutral mutations

Various changes in the genome can lead to mutations that are neutral in terms of selection . On the one hand, the genetic code is degenerate , so that changes in the nucleotide sequence in the nucleic acid do not necessarily lead to changes in the amino acid sequence of a protein . Furthermore, due to similar properties with regard to protein biosynthesis , many amino acid exchanges are largely neutral for the form and function of the protein formed. In addition, large parts of most genomes do not even code for proteins.

Comparisons of various protein-coding genes in humans and in various rodents showed that the rate of synonymous mutations , i.e. those in which the amino acid sequence does not change, is significantly higher than the rate of non-synonymous mutations, i.e. those that are not neutral.

The mutation rate is higher in sequences that do not code for proteins: in the intron of the gene for insulin , the mutation rate is about 6 times higher than in the two exons . This is explained by the fact that such sections are much less subject to selection than the protein-coding ones . Synonymous mutations are equally common in different lines of mammals , while non-synonymous mutations are much rarer in primates than in rodents. The mutation rate is highest in pseudogenes that are not transcribed at all .


An important conclusion from the neutral theory is that neutral mutations occur at a constant rate, at least within similar life forms. The concept of the molecular clock , which is often used in evolutionary research today, is based on this .

For understanding the mechanisms of evolution plays neutral theory especially in explaining the evolvability ( evolvability ) or the ability to self-adaptation ( self-adaptability ) a role. Since neutral mutations do not change biological fitness under the given conditions, they can vary characteristics that become relevant for selection when environmental conditions change. In addition, selection-neutral mutations can influence the potential for a subsequent, selection-relevant change. For example, 9 different nucleic acid triplets code for the amino acid arginine . With CGA, the probability that arginine will continue to be encoded with a point mutation is 4/9. With AGA, however, the probability is 2/9. Despite a neutral effect on the phenotype, a mutation of the first base changes the potential of a further mutation to influence the phenotype.


  • M. Kimura. The Neutral Theory of Molecular Evolution. Cambridge University Press, 1983.
  • Douglas J. Futuyma: Evolution . Sinauer, Sunderland 2005, pp. 235-240. ISBN 0-87893-187-2
  • Naoyuki Takahata: Neutral theory of molecular evolution . In: Current Opinion in Genetics & Development . tape 6 , no. 6 , 1996, pp. 767-772 (English).

Individual evidence

  1. ^ V. Storch, U. Welsch, M. Wink: Evolutionsbiologie . 2nd edition, Springer, Berlin 2007, p. 285 f. ISBN 978-3-540-36072-8