By establishing a compelling case for neutral evolution at the molecular level, Motoo Kimura’s 1968 Nature paper laid an important cornerstone for our modern understanding of biology. While Kimura’s short report has become the canonical citation that biologists use when referencing the neutral theory of evolution, many biologists are unaware of the beautiful way in which it drives to this conclusion by bringing deep theoretical insights to bear on newly obtained empirical evidence.

Let’s begin with some context. In the 1930s and 1940s, biologists unified a Darwinian view of evolution with the emerging field of transmission genetics through intensive theoretical and empirical work across the span of biology. The vision of evolution that emerged from this “modern evolutionary synthesis” was—despite support for the notion of neutral characters in the writings of Charles Darwin, Julian Huxley, Ernst Mayr, and others—predominantly panselectionist. Evolutionary change was taken to be almost exclusively the consequence of natural selection. Where variation was observed, it demanded a selective explanation: either a selective change was underway, or polymorphism was maintained by balancing selection in favor of heterozygous individuals (Gould 1983; Dietrich 1994; Provine 1990).

Bibliography

Avery, O. T., C. M. MacLeod, and M. McCarty. 1944. “Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III.” Journal of Experimental Medicine 79 (2): 137–158. https://doi.org/10.1084/jem.79.2.137.

Dietrich, M. R. 1994. “The Origins of the Neutral Theory of Molecular Evolution.” Journal of the History of Biology 27:21–59. https://doi.org/10.1007/BF01058626.

Doolittle, W. F. 2013. “Is Junk DNA Bunk? A Critique of ENCODE.” Proceedings of the National Academy of Sciences 110 (14): 5294–5300. https://doi.org/10.1073/pnas.1221376110.

Gillespie, J. H. 2000. “Genetic Drift in an Infinite Population: The Pseudohitchhiking Model.” Genetics 155 (2): 909–919. https://doi.org/10.1093/genetics/155.2.909.

Gould, S. J. 1983. “The Hardening of the Modern Synthesis.” In Dimensions of Darwinism, edited by M. Grene. Cambridge, UK: Cambridge University Press.

Haldane, J. B. S. 1957. “The Cost of Natural Selection.” Journal of Genetics 55:511–524. https://doi.org/10.1007/BF02984069.

Hershey, A. D., and M. Chase. 1952. “Independent Functions of Viral Protein and Nucleic Acid in Growth of Bacteriophage.” Journal of General Physiology 36 (1): 39–56. https://doi.org/10.1085/jgp.36.1.39.

Kimura, M. 1960. “Optimum Mutation Rate and Degree of Dominance as Determined by the Principle of Minimum Genetic Load.” Journal of Genetics 57:21–34. https://doi.org/10.1007/BF02985336.

—. 1961. “Natural Selection as the Process of Accumulating Genetic Information in Adaptive Evolution.” Genetical Research 2 (1): 127–140. https://doi.org/10.1017/S0016672300000616.

Kimura, M., and J. F. Crow. 1964. “The Number of Alleles That Can Be Maintained in a Finite Population.” Genetics 49 (4): 725–738. https://doi.org/10.1093/genetics/49.4.725.

Maynard Smith, J. 1968. “‘Haldane’s Dilemma’ and the Rate of Evolution.” Nature 219:1114–1116. https://doi.org/10.1073/pnas.1221376110.

Nirenberg, M. 1968. “Genetic Memory.” JAMA 206 (9): 1973–1977. https://doi.org/10.1001/jama.1968.03150090049012.

Ohta, T. 1992. “The Nearly Neutral Theory of Molecular Evolution.” Annual Review of Ecology and Systematics 23:263–286. https://doi.org/10.1146/annurev.es.23.110192.001403.

Pennisi, E. 2012. “ENCODE Project Writes Eulogy for Junk DNA.” Science 337 (6099): 1159–1161. https://doi.org/10.1126/science.337.6099.1159.

Provine, W. B. 1990. “The Neutral Theory of Molecular Evolution in Historical Perspective.” In Population Biology of Genes and Molecules, edited by N. Takahata and J. F. Crow, 17–31. Tokyo, Japan: Baifukan.

Sved, J. A. 1968. “Possible Rates of Gene Substitution in Evolution.” The American Naturalist 102 (925): 283–293. https://doi.org/10.1086/282542.

Watson, J. D., and F. H. C. Crick. 1953. “Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid.” Nature 171:737–738. https://doi.org/10.1038/171737a0.

Wright, S. 1931. “Evolution in Mendelian Populations.” Genetics 16 (2): 97–159. https://doi.org/10.1093/genetics/16.2.97.

BACK TO Foundational Papers in Complexity Science