Motoo Kimura

Motoo Kimura
Known for	Neutral theory of molecular evolution
Occupation	Geneticist
Institutions	National Institute of Genetics
Field	Population genetics; molecular evolution
Wikidata	Q471816

Motoo Kimura (1924–1994) was a Japanese geneticist and evolutionary biologist best known for formulating the neutral theory of molecular evolution in 1968. He argued that most changes at the level of DNA and proteins are caused by the random fixation of neutral mutations rather than by natural selection. This idea – that genetic drift (random fluctuation in gene variants) dominates molecular change – challenged the prevailing emphasis on adaptive evolution. Kimura’s work, combining mathematical models with emerging molecular data, had a profound and lasting impact on population genetics and evolutionary theory.

Early Life and Education

Kimura was born on November 13, 1924, in Okazaki, Aichi Prefecture, Japan. From childhood he showed a deep interest in nature and plants, and he also had a natural aptitude for mathematics. He attended a selective high school in Nagoya, where he studied plant morphology and chromosome structure under botanist Masa Kumazawa. After Japan’s entry into World War II, Kimura entered Kyoto Imperial University in 1944. On the advice of the prominent geneticist Hitoshi Kihara, he joined the Faculty of Science in the botany program to avoid military drafts. At Kyoto University, Kimura learned the foundations of population genetics, the statistical theory of how gene frequencies change in populations over time.

In 1949 Kimura began his professional career at the National Institute of Genetics in Mishima, Shizuoka, Japan. There he published his first research paper in 1953, introducing a “stepping-stone” model of population structure. This model extended earlier work by the American geneticist Sewall Wright to allow for more complex migration patterns among subpopulations. The same year, a chance meeting inspired Kimura to study abroad. On the recommendation of visiting researchers, he enrolled in graduate school in the United States: first at Iowa State College with animal breeder J. L. Lush in 1953, and then at the University of Wisconsin, Madison, where he completed his PhD under the direction of James F. Crow in 1956. Kimura’s doctoral thesis was titled Stochastic Processes in Population Genetics, reflecting his interest in probability models of gene frequency change.

Kimura then returned to Japan and continued his research at the National Institute of Genetics for the rest of his career. During this period he married Hiroko Kimura and had a son. Throughout his life he remained committed to rigorous quantitative approaches and often collaborated with other leading geneticists, including James Crow, Takeo Maruyama, and Tomoko Ohta.

Major Works and Ideas

In the 1950s and 1960s Kimura developed several foundational models in theoretical population genetics and applied them to molecular data. One of his early contributions was the general model of genetic drift. An allele is a variant form of a gene, and allele frequencies are the proportions of different alleles in a population. Kimura used probability theory (specifically diffusion equations) to calculate how these frequencies change over time by chance, allowing for factors such as natural selection, mutation, and migration. In particular, he derived formulas for the probability of fixation – the chance that a new gene variant eventually spreads to the entire population – under various conditions. These calculations extended earlier ideas by Fisher, Wright, and others into a more general mathematical framework. For example, he showed that when a new mutation is neutral (neither beneficial nor harmful), its chance of eventually becoming fixed in a population is very small (on the order of 1/(2N) in a diploid population of size N), but each of many such neutral mutations contributes to a steady rate of change over time.

Kimura was also co-author (with James Crow) of a seminal model called the infinite-alleles model (1964), which assumed that each new mutation produces a completely novel allele (since a gene might be thousands of DNA bases long, the number of possible alleles is effectively infinite). This model provided a mathematical description of genetic diversity: Kimura and Crow showed that the expected proportion of genetic variation within a species depends on the mutation rate and the effective population size. In this way, their work helped explain patterns of DNA and protein variation that were beginning to be measured in natural populations. Similarly, Kimura introduced the infinite-sites model (in collaboration with Tomoko Ohta) to describe DNA sequence variation: this assumes each mutation occurs at a unique site on the genome, simplifying calculations of how genetic sequences differ. He also formulated the stepwise mutation model (with Ohta), to explain variation in traits that change in discrete steps (like lengths of repeated DNA segments or charges on proteins). These models became widely used tools in molecular evolution and forensic genetics.

The most famous of Kimura’s ideas is the neutral theory of molecular evolution. In 1968 he published a paper titled “Evolutionary Rate at the Molecular Level,” and later expanded it into his 1983 book The Neutral Theory of Molecular Evolution. The core claim of neutral theory is that most evolutionary changes in proteins and DNA are not caused by natural selection favoring advantageous mutations. Instead, Kimura argued, most new mutations are neutral — they have no effect on an organism’s fitness. Because these neutral mutations do not help or harm survival, they are subject to random genetic drift. Over generations, some neutral mutations will become fixed purely by chance, while most will disappear. Crucially, Kimura pointed out that for purely neutral mutations, the expected rate at which they become fixed in a population is equal to the mutation rate. In simpler terms: if organisms of a species experience, say, one neutral mutation per gene per generation on average, then roughly one new neutral mutation will become the new standard allele each generation. This implies a roughly constant rate of change at the molecular level, regardless of population size — an insight that provided a theoretical basis for the “molecular clock” concept introduced by others. In the neutral theory framework, then, the DNA differences among species accumulate at a steady pace that reflects the mutations arising over time, not the intensity of natural selection.

Kimura’s neutral theory also addressed the problem of genetic load. The genetic load is a measure of the cost to a population of replacing alleles through selection — if every mutation had to be either beneficial or harmful, purifying selection would be needed to eliminate deleterious changes constantly, which could theoretically slow adaptation. Kimura showed that if most mutations are neutral, then this load is much lower: harmful mutations are rare and removed by selection, advantageous mutations are rare and swept by selection, and the majority are neutral drift. Thus, neutral theory helped resolve questions about how quickly populations could evolve without accumulating too much genetic “baggage.”

Throughout his career, Kimura published many important papers and books. Besides the landmark 1968 paper and 1983 monograph on neutral theory, his notable works include An Introduction to Population Genetics Theory (1964; later editions), which summarized many of the mathematical foundations of the field. He also wrote a popular science book My Views on Evolution (1988, in Japanese) that presented his perspective to a general audience. Overall, Kimura’s ideas reshaped how scientists thought about evolution on a genetic level: he showed that statistical models of mutation and drift could explain much of the observed molecular diversity, and he advanced a null model of evolution that remains a central reference point in genetics.

Methodology and Approach

Kimura was fundamentally a theoretical population geneticist who used advanced mathematics to tackle biological problems. His method was to combine statistical models with empirical data from DNA and protein studies. One of his primary tools was the diffusion equation, a concept borrowed from physics to describe the random motion of particles. In genetics, the diffusion equation can approximate the random fluctuation of allele frequencies from generation to generation. Kimura adapted this tool (along with the related Kolmogorov forward and backward equations) to derive formulas for the fate of genes under random drift. He demonstrated that these equations could yield practical predictions, such as the probability that a given copy of a gene out of many will eventually spread through the whole population (fixation).

Using these probabilistic techniques, Kimura developed key results such as the rate of neutral substitution and the expected amount of genetic variation at equilibrium. For instance, he showed that the average proportion of different gene variants (heterozygosity) in a population depends on the product of population size and mutation rate. These results allowed scientists to connect measurable quantities (like mutation rates and genetic diversity) to fundamental evolutionary processes.

In practice, Kimura’s work often involved deriving equations and then checking their implications against biological knowledge. He collaborated with colleagues who provided different perspectives – for example, James Crow on general allele models, and Tomoko Ohta on models with nearly neutral mutations. Kimura’s approach was also strongly data-driven in that he paid close attention to new findings in protein sequencing and DNA biochemistry. When he saw that molecular data (such as amino acid substitutions and DNA sequences) were accumulating quickly in the 1960s, he used his theory to interpret these trends. In this way, he brought together the often separate worlds of molecular biology and population genetics.

Kimura’s clarity of mathematical logic was a hallmark of his method. He strove to make his models as simple as possible while capturing the essential features of mutation, selection, and drift. This simplicity made his ideas influential: his neutral theory provided a relatively straightforward baseline model that other researchers could test against real data. In effect, he turned theoretical population genetics into a quantitative science with predictive power. This was in contrast to earlier, more qualitative treatments of evolution, and it gave rigorous support to molecular evolution as its own discipline.

Influence on Evolutionary Biology

Kimura’s influence on genetics and evolution is immense. By introducing the neutral theory, he effectively founded the field of molecular evolution as we know it. His ideas prompted generations of biologists to ask new questions about how genes change over time. For example, the concept that most DNA differences are neutral led to widespread use of genetic markers for studying population history, without assuming those markers were adaptive. In conservation and ecology, his models helped researchers interpret patterns of variation in endangered species, and in human genetics they influenced studies of human origins.

Many subsequent discoveries and tools have roots in Kimura’s work. The molecular clock idea, which estimates how long ago two species diverged by comparing DNA changes, is based on neutral theory’s prediction of a roughly constant rate of neutral substitutions. Methods for testing neutrality (such as Tajima’s D and related statistics) were developed to distinguish random drift from selection, using Kimura’s models as the null hypothesis. In essence, his theory became the “default” scenario for genetic change: if data strongly deviated from neutrality, one could infer that selection or other forces were at play.

Esteemed geneticists have praised Kimura’s contributions. James F. Crow (Kimura’s mentor) later remarked that Kimura was one of the greatest evolutionary geneticists of the 20th century. The neutral theory also influenced thinkers beyond traditional genetics. It provided a rationale for understanding molecular evolution in areas like virology (how viruses evolve), cancer genetics (how mutations accumulate in cells), and even computer science (in the theory of genetic algorithms). Theoreticians such as Motoo Kimura shaped textbooks and curricula: today any course on evolution or genetics covers neutral drift partly because of Kimura.

The international scientific community recognized Kimura with numerous awards and honors, reflecting his influence. In 1992 he received the Darwin Medal from the United Kingdom’s Royal Society, one of the highest honors in evolutionary biology. He was elected a foreign associate of the U.S. National Academy of Sciences and a foreign member of the Royal Society of London. In Japan he was a member of the Japan Academy and was decorated with the Order of Culture. These honors show that Kimura’s peers saw his work as fundamentally advancing the field.

Critiques and Controversies

Kimura’s neutral theory was controversial from the start because it contradicted the longstanding assumption that natural selection drives most evolution. Many evolutionary biologists, especially traditionalists, criticized the idea that random drift could be so important. Critics argued that Kimura had minimized the role of selection: surely many gene changes affect an organism’s fitness, they said, and these should not be ignored. Some critics also pointed out that Kimura’s original statement of the theory was qualitative, not giving a precise fraction of mutations that are neutral. This made it hard to compare with data. As one biologist quipped, Kimura lacked a clear numerical threshold for “appreciable fraction,” so in theory any new evidence could be interpreted as consistent with neutrality.

In response to such criticisms, the debate between neutralists and selectionists became a major theme in evolutionary genetics in the 1970s and 1980s. Selectionists like the biologist John Maynard Smith argued that adaptive evolution could explain many patterns that neutral theory attributed to drift. They developed models showing that even with selection, one could see some of the same signatures in DNA. At the same time, empiricists accumulated more molecular data. Studies of DNA, proteins, and genomes began to reveal cases where natural selection clearly left its mark (for example, regions of DNA highly conserved across species, or patterns of variation indicating recent sweeps of advantageous mutations). These findings suggested that adaptation at the molecular level might be more common than a strictly neutral view predicted.

Kimura and his allies were not blind to these issues. In fact, one of his colleagues, Tomoko Ohta, modified the theory to account for “nearly neutral” mutations in the 1970s. The nearly neutral theory says that many mutations are not strictly neutral but slightly harmful or beneficial; whether they drift or are selected depends on population size. If the effective population is small, even slightly deleterious mutations can drift to fixation. Ohta’s work extended Kimura’s ideas, and in practice today the neutral and nearly neutral theories are often grouped together. They form a baseline for understanding the relative contributions of drift and selection.

Even with such refinements, debates continue. Some modern researchers argue that recent genome-wide data show more pervasive selection than once thought. Other ecologists and philosophers have questioned whether the neutralist-selectionist framework is enough, proposing new models. However, these discussions generally treat neutral theory as a starting point rather than dismissing it. In practice, Kimura’s theory offered a null hypothesis: if observed genetic patterns fit neutral expectations, drift must be considered important; if not, selection or other forces are implicated. In this way, neutral theory shaped research more by offering tools for study than by being an unquestioned doctrine.

Legacy

Kimura passed away on November 13, 1994 (his 70th birthday) after a lifetime of intellectual work. His legacy is secure in the annals of science. The neutral theory of molecular evolution is now a foundational concept taught in textbooks worldwide. Even critics acknowledge that Kimura forced a paradigm shift: by highlighting the role of random processes, he broadened the view of evolution beyond strict adaptation.

Today, one can still feel Kimura’s influence in many ways. Practice of molecular evolution routinely considers neutral drift as a key factor. Conservation biologists use neutral genetic variation to assess population health and history. Molecular clocks based on neutral mutations are standard tools for dating evolutionary events (with calibration). The theoretical framework he built is still actively extended: for example, modern population genetics incorporates neutral models into coalescent theory and into genome-wide scans for selection.

Kimura’s example as a scientist also resonates. He combined deep mathematical reasoning with an appreciation of biological complexity, and he stood by his ideas through heated debate. His many honors — such as the Darwin Medal and membership in the world’s leading academies — reflect the esteem in which he was held. Colleagues remember him as a generous collaborator and a brilliant thinker. In sum, Motoo Kimura transformed our understanding of evolutionary genetics, and his work remains a cornerstone of how scientists study gene and genome evolution.

Selected Works

Kimura, M. (1953). “Stepping Stone Model of Population Structure.” Journal of Genetics 47: 132–147. [On population models with local migration.]
Kimura, M. (1961). “Some Calculations on the Mutational Load.” Japanese Journal of Genetics 36: 179–190. [Analysis of genetic load under mutation and selection.]
Kimura, M. (1964). An Introduction to Population Genetics Theory. [Textbook summarizing theoretical population genetics.]
Crow, J. F. & Kimura, M. (1970). “An Introduction to Genetic Population Structure.” [Work on genetic drift and diversity models.]
Kimura, M. (1968). “Evolutionary Rate at the Molecular Level.” Nature 217: 624–626. [Original paper proposing the neutral theory.]
Kimura, M. & Ohta, T. (1973). “The Age of a Neutral Mutant That Has Segregated in a Finite Population.” Genetics 75: 199–212. [Mathematical details of nearly neutral mutation.]
Kimura, M. (1983). The Neutral Theory of Molecular Evolution. Cambridge University Press. [Comprehensive monograph on neutral theory.]
Kimura, M. (1988). Seibutsu shinka wo kangaeru (My Views on Evolution). Iwanami Shoten. [Popular book on evolutionary thought.]

Timeline of Key Events

1924 – Born on November 13 in Okazaki, Japan.
1944 – Entered Kyoto Imperial University to study botany and genetics.
1949 – Joined the National Institute of Genetics (NIG) in Mishima, Japan.
1953 – Published the “stepping-stone” model of population structure; moved to the USA for graduate studies.
1956 – Received PhD from University of Wisconsin under James F. Crow; thesis on stochastic processes in population genetics.
1964 – Co-authored work on the infinite-alleles model (with Crow); published An Introduction to Population Genetics Theory.
1968 – Published the paper introducing the neutral theory of molecular evolution.
1976 – Awarded Japan’s Order of Culture for contributions to genetics.
1983 – Published The Neutral Theory of Molecular Evolution (book).
1986–1988 – Received major prizes, including the Asahi Prize and International Prize for Biology.
1992 – Awarded the Darwin Medal by the Royal Society.
1993 – Elected Foreign Member of the Royal Society of London.
1994 – Died on November 13 in Mishima, Shizuoka, Japan (his 70th birthday).