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Kimura, Motoo
Kimura, Motoo TY Steen, The Library of Congress, Washington, DC, USA and Johns Hopkins University, Baltimore, MD, USA
© 2013 Elsevier Inc. All rights reserved.
This article is a revision of the previous edition article by JF Crow, volume 1, pp 1062–1063, © 2001, Elsevier Inc.
Glossary Diffusion equation A partial differential equation which describes fluctuations of density in a subject undergoing diffusion. In population genetics, it is also used to describe processes exhibiting diffusive-like behavior, for example, the diffusion of alleles in a population. Effective population size (Ne) A concept in population genetics introduced by Sewall Wright. He defined it as “the number of breeding individuals in an idealized population that would show the same amount of dispersion of allele frequencies under random genetic drift or the same amount of inbreeding as the population under consideration.” It is a basic parameter in many models in population genetics. The effective population size is usually smaller than the absolute population size (N). Genetic load (L) A type of genetic burden, a value of the cost of lost alleles due to selection (selection load) or mutation (mutational load). It is a value in the range 0 < L < 1, where 0 represents no load. This concept was first formulated in 1937 by J.B.S. Haldane, independently formulated, named, and applied to humans in 1950 by H.J. Muller, and revised by Haldane in 1957. Molecular evolutionary clock A method in molecular evolution that uses fossil constraints and rates of molecular change to deduce the time in geologic history when two species or other taxa diverged. It is used to estimate the time of occurrence of events called speciation or radiation. The molecular data used for such calculations are usually nucleotide sequences for DNA or amino acid sequences for proteins. The concept was first proposed by Emile Zuckerkandl and Linus Pauling in 1962.
Introduction Motoo Kimura (1924–94) (Figure 1) was a population geneti cist who contributed to the development of the field of molecular evolutionary biology, and is best known as an advo cate of the neutral theory of molecular evolution with his paper in the journal Nature (1968). A year later, Jack King and Thomas Jukes, who also reached the same conclusion about the same time as Kimura, published their work in Science (1969). The phrase ‘neutral theory of molecular evolution’ was invented by Kimura. Kimura’s paper in Nature rather than King and Jukes’ in Science has been cited much more frequently over the years, and it was Kimura who fought the battles of the selectionist–neutralist controversy throughout his life. Although both Kimura and the team of King and Jukes arrived at the same conclusion of the neutral theory, these two parties arrived at this conclusion from different paths. While Kimura arrived at his conclusion through his mathematical
156
Nearly neutral theory of molecular evolution A modification of the neutral theory of molecular evolution that accounts for slightly advantageous or deleterious mutations at the molecular level. The nearly neutral theory was proposed by Tomoko Ohta in 1973 (including only deleterious mutations) and expanded in the early 1990s to include both advantageous and deleterious nearly neutral mutations. Neutral theory of molecular evolution A hypothesis that the vast majority of evolutionary changes at the molecular level are caused by random genetic drift based on selectively neutral mutations. The theory was introduced by Motoo Kimura in 1968. Random genetic drift The random change in the frequency of a gene variant (allele) in a population due to all the sampling processes that occur in each generation. Sampling processes are associated with survival, reproduction and fecundity. The alleles in the offspring are a sample of those in the parents, and chance has a role in determining whether a given individual survives and reproduces. A population’s allele frequency is the fraction of the copies of one gene that share a particular form. Random genetic drift is an important evolutionary process, which leads to changes in allele frequencies over time. Selectionist-neutralist controversy A heated debate started since the publication of the neutral theory in 1968 by Motoo Kimura and 1969 by Jack King and Thomas Jukes. The center of discussion for this controversy is the relative percentages of alleles that are neutral or non-neutral in any given genome. The debate was not about whether or not natural selection acts at all.
calculations, King and Jukes arrived at theirs through their biochemical studies of mutations. Kimura modified his theory over the years as new molecular data appeared. Among his many publications, Kimura’s most influential publications that describe these successions include: ‘Evolutionary rate at the molecular level’ in Nature (1968); The Neutral Theory of Molecular Evolution (The Cambridge University Press, 1983), and Seibutsu shinka wo kangaeru (My Views on Evolution) (Iwanami Shoten, 1988). Kimura was the one who introduced the field of population genetics to Japan in the early 1960s by translating the English word to Japanese words, syudan iden gaku, after studying the subject on his own and then in graduate schools in the United States. He was elected a foreign member of the National Academy of Sciences (USA) and received the John J. Carty Award for the Advancement of Science in 1987 (Figure 2), and received the International Prize for Biology in 1988 (Figure 3). Before his death in 1994, Kimura achieved one of the top honors in the
Brenner’s Encyclopedia of Genetics, 2nd Edition, Volume 4
doi:10.1016/B978-0-12-374984-0.00832-9
Kimura, Motoo
157
Figure 1 Kimura and the author in front of the banners he designed in his office at the National Institute of genetics. Photo courtesy: Dr. Katsumi Kimura.
Figure 4 Darwin Medal (front and back), 1992. Photo courtesy: Dr. Katsumi Kimura.
Figure 2 The John J. Carty Award for the Advancement of Science (USA), 1987. Photo courtesy: Dr. Katsumi Kimura.
Even as a young child Kimura had many eccentric ideas in science. Throughout his life, he often confronted unsympa thetic audiences or colleagues in order to put across his ideas. Yet, he hoped to avoid conflict as he believed that his ideas would come through if he was lucky – he coined the phrase ‘survival of the luckiest!’ He continued to elaborate his theory of neutral mutation throughout his life. The onset of amyo trophic lateral sclerosis led to paralysis of limbs which contributed to a fall and a head injury, which cut short his life on his 70th birthday, 13 November 1994. He was always concerned about restrictive systems of science and math educa tion in Japan and hoped to improve science education through his contribution to younger generations.
The Life of the Pioneering Scientist Childhood and Education
Figure 3 International Prize for Biology, with Mrs. Hiroko Kimura, 1988. Photo courtesy: Dr. Katsumi Kimura.
field of evolutionary biology when he received the Darwin Medal (Figure 4) from the Royal Society of London for the Improvement of Natural Knowledge (1992); a year later, he became a member of the Society (1993).
Motoo Kimura was born on 13 November 1924 in the castle town of Okazaki, near Nagoya City of the Aichi Prefecture. His father hailed from a well-known family of metal artisans who made large temple bells; his mother hailed from a family of wealthy sake and soy sauce brewers. He often described his parents by saying “My parents were just like the ones in Thomas Mann’s novel Tonio Kroger. ‘My father was thoughtful but stubborn, while my mother was artful and optimistic’.” Taking his mother’s character, Kimura was artful, optimistic, and also outspoken. Yet, like his father, Kimura was thoughtful,
158
Kimura, Motoo
but stubborn or persistent at the same time. These combined characters helped Kimura to push the neutral theory forward throughout his career. He often stated that he did not like controversy. He simply did not know he was entering into the large controversy of the selectionists–neutralists when he ori ginally proposed the neutral theory. Kimura attended primary schools during war time where he was expected to simply obey his teachers. He often irritated them by asking questions and was considered to be a bad student. However, in his fifth grade, he met an open-minded and dedicated teacher who changed the course of Kimura’s life and rekindled his original interest in botany. Kimura decided to continue his study at the Okazaki Middle School in 1937. Again there, Kimura met another dedicated teacher and he took on a private project of collecting plants. Kimura was so focused on this project that school friends called him Professor Botany! During the third year in the middle school, a pivotal inci dent of his life occurred: he lost his younger brother, who died of food poisoning. Confined to bed himself, Kimura’s self-study led to a growing interest in mathematics. As he developed interests in both math and botany, he established his foundation of population genetics. In 1942, Kimura went to the Eighth High School, now Nagoya University, where he met a plant morphologist, Masao Kumazawa. Under Kumazawa, Kimura focused on plant morphology and cytology and worked on the chromo some structure of lilies. In 1944, Kimura entered Kyoto Imperial University and he was keen to study under Hitoshi Kihara, then most prominent cyto-geneticist at the Department of Agriculture. However, Kimura was advised by Kihara to enter the botany courses in the Faculty of Science rather than the cytology courses under the Department of Agriculture to avoid being drafted into the military. After the war, Kimura joined Kihara’s laboratory, where he studied the introduction of for eign chromosomes into plants and taught himself population genetics through reading papers by J.B.S. Haldane, R.A. Fisher, and S. Wright, internationally know population geneticists. In 1949, Kimura joined the National Institute of Genetics (NIG) in Mishima, Shizuoka. In 1953, he published his first population genetics paper, describing a stepping-stone model for population structure that was more capable of dealing with complex patterns of allele migration than Sewall Wright’s ear lier ‘island model’. While he was at NIG, Kimura met the Canadian geneticist Duncan McDonald who worked for the Atomic Bomb Casualty Commission. McDonald recognized Kimura’s extraordinary skills in mathematics and genetics, and arranged for him to enter graduate school at Iowa State College in summer of 1953 to study with J.L. Lush. However, Kimura quickly found Iowa State College too restricting, and moved to the University of Wisconsin to work with James F. Crow, where he had a chance to meet Sewall Wright. In 1955, Kimura gave a first international paper at the Cold Spring Harbor Symposium. Although few were able to under stand Kimura’s paper, it was praised by Wright and Haldane. His accomplishments at Wisconsin included a model for genetic drift, which could accommodate multiple alleles, selec tion, migration, and mutations, using R.A. Fisher’s fundamental theorem of natural selection. He also built on the work of Wright with the Fokker–Planck equation by intro ducing the Kolmogorov backward equation to population
Figure 5 William Provine and Tomoko Ohta.
genetics, allowing the calculation of the probability of a gene to become fixed in a population. He received his PhD in 1956 and returned to Japan. Kimura worked on a wide spectrum of theoretical problems in population genetics, in collaboration with Takeo Maruyama during the 1960s and then with Tomoko Ohta (Figure 5) from the late 1960s to the 1980s. Kimura became known for his pioneering work using diffusion equations to calculate the prob abilities of fixation of beneficial, deleterious, or neutral alleles. He introduced the ‘infinite allele’ and ‘infinite site’ models for the study of genetic drift, both of which would be used widely as the field of molecular evolution grew alongside the number of avail able peptide and gene sequences. He also created the ‘ladder model’ that could be applied to electrophoresis studies where homologous proteins differ by whole units of charge. An early statement of his approach was published in 1960, in his An Introduction to Population Genetics Theory that he wrote with James F. Crow. He also contributed an important review article on the ongoing controversy over genetic load in 1961 with Crow.
The Selectionist–Neutralist Controversy The period 1967–68 marked a turning point in Kimura’s career. Toward the end of 1967, he formulated his neutral theory: the large majority of genetic change is neutral with respect to natural selection, making random genetic drift a primary factor in evolution. Using theoretical population genetics calcula tions, he analyzed molecular evolutionary data that became available through studies of the molecular evolutionary clock. He realized that if genetic load is as heavy as Haldane argued previously, none of the species would survive. Thus, he devel oped the neutral theory – the idea that genetic drift rather than selection is the main force of changing allele frequencies. The neutral theory, first published in Nature, became controversial immediately, receiving support from molecular biologists and drawing opposition from Darwinians. Kimura spent the rest of his life developing and defending the neutral theory. As his mentor James Crow put it, “much of Kimura’s early work turned out to be pre-adapted for use in the quantitative study of neutral evolution” (based on an interview by the author on March 1993). As new experimental techni ques and genetic knowledge became available, Kimura
Kimura, Motoo expanded the scope of the neutral theory and created mathe matical methods for testing it against the available evidence. In 1973, his colleague Tomoko Ohta developed a modified ver sion of the theory, the ‘nearly neutral theory’ that could account for high volumes of slightly deleterious mutations. In 1983, Kimura published a monograph on the neutral theory, The Neutral Theory of Molecular Evolution, and also worked to pro mote the theory through popular writings such as My Views on Evolution, a book that became a best seller in Japan.
Kimura’s Dream: The Four-Step Scenario As evolutionary studies at the molecular level develop further, a question arises: How one would apply molecular level evo lution to phenotypic evolution? At the same time, in conference presentations, molecular evolutionists started to call the neutral theory the ‘null hypothesis’ (Kreitman, M., 1996). Toward the end of his life, Kimura was pondering the possibility of linking molecular-level evolution to phenotypic evolution and named it ‘the four-step scenario’ (yon dankai setsu) and published this idea in 1991. However, his time was too short to elaborate on this hypothesis. He died on 13 November 1994.
See also: Genetic Drift; Genetic Load; Molecular Clock; Nearly Neutral Theory; Neutral Theory.
159
Further Reading Kimura M (1968) Evolutionary rate at the molecular level Nature 217(5129): 624–626. Kimura M (1983) The Neutral Theory of Molecular Evolution. Cambridge: Cambridge University Press. Kimura M (1988) (in Japanese). Seibutsu shinka wo kangaeru (My Views on Evolution). Tokyo: Iwanami Shoten. Kimura M (1989) The neutral theory of molecular evolution and the world view of the neutralists. Genome. 31(1): 24–31. Kimura M (1991) Recent development of the neutral theory viewed from the Wrightian tradition of theoretical population genetics. Proceedings of the National Academy of Sciences of the United States of America 88: 5969–5973. Kimura, M (under review) My Views on Evolution. Translated by Steen, TY. Chicago: University of Chicago Press. King JL and Jukes TH (1969). Non-Darwinian evolution. Science 164(3881): 788–798. Kreitman M (1996) The neutral theory is dead. Long live the neutral theory. BioEssays 18(8): 678–683. Ohta T (1973) Slightly deleterious mutant substitutions in evolution. Nature 246: 96–98. Ohta T and Gillespie JH (1996) Development of neutral and nearly neutral theories. Theoretical Population Biology 49(2): 128–142. Steen TY (1996) Tomoko Ohta and the Nearly Neutral Theories: The Role of a Female Geneticist in the Neutralist-Selectionist Controversy/ Ph.D. Dissertation. (CORNELL UNIVERSITY) Steen TY (1996) Always an eccentric? A brief biography of Motoo Kimura. Journal of Genetics 75(1): 19–25.
Relevant Websites http://authors.library.caltech.edu– History of Recent Science and Technology: Perspectives on Molecular Evolution – Fitch and the Heretic Kimura.
© 2013 Elsevier Inc. All rights reserved.
This article is a revision of the previous edition article by JF Crow, volume 1, pp 1062–1063, © 2001, Elsevier Inc.
Glossary Diffusion equation A partial differential equation which describes fluctuations of density in a subject undergoing diffusion. In population genetics, it is also used to describe processes exhibiting diffusive-like behavior, for example, the diffusion of alleles in a population. Effective population size (Ne) A concept in population genetics introduced by Sewall Wright. He defined it as “the number of breeding individuals in an idealized population that would show the same amount of dispersion of allele frequencies under random genetic drift or the same amount of inbreeding as the population under consideration.” It is a basic parameter in many models in population genetics. The effective population size is usually smaller than the absolute population size (N). Genetic load (L) A type of genetic burden, a value of the cost of lost alleles due to selection (selection load) or mutation (mutational load). It is a value in the range 0 < L < 1, where 0 represents no load. This concept was first formulated in 1937 by J.B.S. Haldane, independently formulated, named, and applied to humans in 1950 by H.J. Muller, and revised by Haldane in 1957. Molecular evolutionary clock A method in molecular evolution that uses fossil constraints and rates of molecular change to deduce the time in geologic history when two species or other taxa diverged. It is used to estimate the time of occurrence of events called speciation or radiation. The molecular data used for such calculations are usually nucleotide sequences for DNA or amino acid sequences for proteins. The concept was first proposed by Emile Zuckerkandl and Linus Pauling in 1962.
Introduction Motoo Kimura (1924–94) (Figure 1) was a population geneti cist who contributed to the development of the field of molecular evolutionary biology, and is best known as an advo cate of the neutral theory of molecular evolution with his paper in the journal Nature (1968). A year later, Jack King and Thomas Jukes, who also reached the same conclusion about the same time as Kimura, published their work in Science (1969). The phrase ‘neutral theory of molecular evolution’ was invented by Kimura. Kimura’s paper in Nature rather than King and Jukes’ in Science has been cited much more frequently over the years, and it was Kimura who fought the battles of the selectionist–neutralist controversy throughout his life. Although both Kimura and the team of King and Jukes arrived at the same conclusion of the neutral theory, these two parties arrived at this conclusion from different paths. While Kimura arrived at his conclusion through his mathematical
156
Nearly neutral theory of molecular evolution A modification of the neutral theory of molecular evolution that accounts for slightly advantageous or deleterious mutations at the molecular level. The nearly neutral theory was proposed by Tomoko Ohta in 1973 (including only deleterious mutations) and expanded in the early 1990s to include both advantageous and deleterious nearly neutral mutations. Neutral theory of molecular evolution A hypothesis that the vast majority of evolutionary changes at the molecular level are caused by random genetic drift based on selectively neutral mutations. The theory was introduced by Motoo Kimura in 1968. Random genetic drift The random change in the frequency of a gene variant (allele) in a population due to all the sampling processes that occur in each generation. Sampling processes are associated with survival, reproduction and fecundity. The alleles in the offspring are a sample of those in the parents, and chance has a role in determining whether a given individual survives and reproduces. A population’s allele frequency is the fraction of the copies of one gene that share a particular form. Random genetic drift is an important evolutionary process, which leads to changes in allele frequencies over time. Selectionist-neutralist controversy A heated debate started since the publication of the neutral theory in 1968 by Motoo Kimura and 1969 by Jack King and Thomas Jukes. The center of discussion for this controversy is the relative percentages of alleles that are neutral or non-neutral in any given genome. The debate was not about whether or not natural selection acts at all.
calculations, King and Jukes arrived at theirs through their biochemical studies of mutations. Kimura modified his theory over the years as new molecular data appeared. Among his many publications, Kimura’s most influential publications that describe these successions include: ‘Evolutionary rate at the molecular level’ in Nature (1968); The Neutral Theory of Molecular Evolution (The Cambridge University Press, 1983), and Seibutsu shinka wo kangaeru (My Views on Evolution) (Iwanami Shoten, 1988). Kimura was the one who introduced the field of population genetics to Japan in the early 1960s by translating the English word to Japanese words, syudan iden gaku, after studying the subject on his own and then in graduate schools in the United States. He was elected a foreign member of the National Academy of Sciences (USA) and received the John J. Carty Award for the Advancement of Science in 1987 (Figure 2), and received the International Prize for Biology in 1988 (Figure 3). Before his death in 1994, Kimura achieved one of the top honors in the
Brenner’s Encyclopedia of Genetics, 2nd Edition, Volume 4
doi:10.1016/B978-0-12-374984-0.00832-9
Kimura, Motoo
157
Figure 1 Kimura and the author in front of the banners he designed in his office at the National Institute of genetics. Photo courtesy: Dr. Katsumi Kimura.
Figure 4 Darwin Medal (front and back), 1992. Photo courtesy: Dr. Katsumi Kimura.
Figure 2 The John J. Carty Award for the Advancement of Science (USA), 1987. Photo courtesy: Dr. Katsumi Kimura.
Even as a young child Kimura had many eccentric ideas in science. Throughout his life, he often confronted unsympa thetic audiences or colleagues in order to put across his ideas. Yet, he hoped to avoid conflict as he believed that his ideas would come through if he was lucky – he coined the phrase ‘survival of the luckiest!’ He continued to elaborate his theory of neutral mutation throughout his life. The onset of amyo trophic lateral sclerosis led to paralysis of limbs which contributed to a fall and a head injury, which cut short his life on his 70th birthday, 13 November 1994. He was always concerned about restrictive systems of science and math educa tion in Japan and hoped to improve science education through his contribution to younger generations.
The Life of the Pioneering Scientist Childhood and Education
Figure 3 International Prize for Biology, with Mrs. Hiroko Kimura, 1988. Photo courtesy: Dr. Katsumi Kimura.
field of evolutionary biology when he received the Darwin Medal (Figure 4) from the Royal Society of London for the Improvement of Natural Knowledge (1992); a year later, he became a member of the Society (1993).
Motoo Kimura was born on 13 November 1924 in the castle town of Okazaki, near Nagoya City of the Aichi Prefecture. His father hailed from a well-known family of metal artisans who made large temple bells; his mother hailed from a family of wealthy sake and soy sauce brewers. He often described his parents by saying “My parents were just like the ones in Thomas Mann’s novel Tonio Kroger. ‘My father was thoughtful but stubborn, while my mother was artful and optimistic’.” Taking his mother’s character, Kimura was artful, optimistic, and also outspoken. Yet, like his father, Kimura was thoughtful,
158
Kimura, Motoo
but stubborn or persistent at the same time. These combined characters helped Kimura to push the neutral theory forward throughout his career. He often stated that he did not like controversy. He simply did not know he was entering into the large controversy of the selectionists–neutralists when he ori ginally proposed the neutral theory. Kimura attended primary schools during war time where he was expected to simply obey his teachers. He often irritated them by asking questions and was considered to be a bad student. However, in his fifth grade, he met an open-minded and dedicated teacher who changed the course of Kimura’s life and rekindled his original interest in botany. Kimura decided to continue his study at the Okazaki Middle School in 1937. Again there, Kimura met another dedicated teacher and he took on a private project of collecting plants. Kimura was so focused on this project that school friends called him Professor Botany! During the third year in the middle school, a pivotal inci dent of his life occurred: he lost his younger brother, who died of food poisoning. Confined to bed himself, Kimura’s self-study led to a growing interest in mathematics. As he developed interests in both math and botany, he established his foundation of population genetics. In 1942, Kimura went to the Eighth High School, now Nagoya University, where he met a plant morphologist, Masao Kumazawa. Under Kumazawa, Kimura focused on plant morphology and cytology and worked on the chromo some structure of lilies. In 1944, Kimura entered Kyoto Imperial University and he was keen to study under Hitoshi Kihara, then most prominent cyto-geneticist at the Department of Agriculture. However, Kimura was advised by Kihara to enter the botany courses in the Faculty of Science rather than the cytology courses under the Department of Agriculture to avoid being drafted into the military. After the war, Kimura joined Kihara’s laboratory, where he studied the introduction of for eign chromosomes into plants and taught himself population genetics through reading papers by J.B.S. Haldane, R.A. Fisher, and S. Wright, internationally know population geneticists. In 1949, Kimura joined the National Institute of Genetics (NIG) in Mishima, Shizuoka. In 1953, he published his first population genetics paper, describing a stepping-stone model for population structure that was more capable of dealing with complex patterns of allele migration than Sewall Wright’s ear lier ‘island model’. While he was at NIG, Kimura met the Canadian geneticist Duncan McDonald who worked for the Atomic Bomb Casualty Commission. McDonald recognized Kimura’s extraordinary skills in mathematics and genetics, and arranged for him to enter graduate school at Iowa State College in summer of 1953 to study with J.L. Lush. However, Kimura quickly found Iowa State College too restricting, and moved to the University of Wisconsin to work with James F. Crow, where he had a chance to meet Sewall Wright. In 1955, Kimura gave a first international paper at the Cold Spring Harbor Symposium. Although few were able to under stand Kimura’s paper, it was praised by Wright and Haldane. His accomplishments at Wisconsin included a model for genetic drift, which could accommodate multiple alleles, selec tion, migration, and mutations, using R.A. Fisher’s fundamental theorem of natural selection. He also built on the work of Wright with the Fokker–Planck equation by intro ducing the Kolmogorov backward equation to population
Figure 5 William Provine and Tomoko Ohta.
genetics, allowing the calculation of the probability of a gene to become fixed in a population. He received his PhD in 1956 and returned to Japan. Kimura worked on a wide spectrum of theoretical problems in population genetics, in collaboration with Takeo Maruyama during the 1960s and then with Tomoko Ohta (Figure 5) from the late 1960s to the 1980s. Kimura became known for his pioneering work using diffusion equations to calculate the prob abilities of fixation of beneficial, deleterious, or neutral alleles. He introduced the ‘infinite allele’ and ‘infinite site’ models for the study of genetic drift, both of which would be used widely as the field of molecular evolution grew alongside the number of avail able peptide and gene sequences. He also created the ‘ladder model’ that could be applied to electrophoresis studies where homologous proteins differ by whole units of charge. An early statement of his approach was published in 1960, in his An Introduction to Population Genetics Theory that he wrote with James F. Crow. He also contributed an important review article on the ongoing controversy over genetic load in 1961 with Crow.
The Selectionist–Neutralist Controversy The period 1967–68 marked a turning point in Kimura’s career. Toward the end of 1967, he formulated his neutral theory: the large majority of genetic change is neutral with respect to natural selection, making random genetic drift a primary factor in evolution. Using theoretical population genetics calcula tions, he analyzed molecular evolutionary data that became available through studies of the molecular evolutionary clock. He realized that if genetic load is as heavy as Haldane argued previously, none of the species would survive. Thus, he devel oped the neutral theory – the idea that genetic drift rather than selection is the main force of changing allele frequencies. The neutral theory, first published in Nature, became controversial immediately, receiving support from molecular biologists and drawing opposition from Darwinians. Kimura spent the rest of his life developing and defending the neutral theory. As his mentor James Crow put it, “much of Kimura’s early work turned out to be pre-adapted for use in the quantitative study of neutral evolution” (based on an interview by the author on March 1993). As new experimental techni ques and genetic knowledge became available, Kimura
Kimura, Motoo expanded the scope of the neutral theory and created mathe matical methods for testing it against the available evidence. In 1973, his colleague Tomoko Ohta developed a modified ver sion of the theory, the ‘nearly neutral theory’ that could account for high volumes of slightly deleterious mutations. In 1983, Kimura published a monograph on the neutral theory, The Neutral Theory of Molecular Evolution, and also worked to pro mote the theory through popular writings such as My Views on Evolution, a book that became a best seller in Japan.
Kimura’s Dream: The Four-Step Scenario As evolutionary studies at the molecular level develop further, a question arises: How one would apply molecular level evo lution to phenotypic evolution? At the same time, in conference presentations, molecular evolutionists started to call the neutral theory the ‘null hypothesis’ (Kreitman, M., 1996). Toward the end of his life, Kimura was pondering the possibility of linking molecular-level evolution to phenotypic evolution and named it ‘the four-step scenario’ (yon dankai setsu) and published this idea in 1991. However, his time was too short to elaborate on this hypothesis. He died on 13 November 1994.
See also: Genetic Drift; Genetic Load; Molecular Clock; Nearly Neutral Theory; Neutral Theory.
159
Further Reading Kimura M (1968) Evolutionary rate at the molecular level Nature 217(5129): 624–626. Kimura M (1983) The Neutral Theory of Molecular Evolution. Cambridge: Cambridge University Press. Kimura M (1988) (in Japanese). Seibutsu shinka wo kangaeru (My Views on Evolution). Tokyo: Iwanami Shoten. Kimura M (1989) The neutral theory of molecular evolution and the world view of the neutralists. Genome. 31(1): 24–31. Kimura M (1991) Recent development of the neutral theory viewed from the Wrightian tradition of theoretical population genetics. Proceedings of the National Academy of Sciences of the United States of America 88: 5969–5973. Kimura, M (under review) My Views on Evolution. Translated by Steen, TY. Chicago: University of Chicago Press. King JL and Jukes TH (1969). Non-Darwinian evolution. Science 164(3881): 788–798. Kreitman M (1996) The neutral theory is dead. Long live the neutral theory. BioEssays 18(8): 678–683. Ohta T (1973) Slightly deleterious mutant substitutions in evolution. Nature 246: 96–98. Ohta T and Gillespie JH (1996) Development of neutral and nearly neutral theories. Theoretical Population Biology 49(2): 128–142. Steen TY (1996) Tomoko Ohta and the Nearly Neutral Theories: The Role of a Female Geneticist in the Neutralist-Selectionist Controversy/ Ph.D. Dissertation. (CORNELL UNIVERSITY) Steen TY (1996) Always an eccentric? A brief biography of Motoo Kimura. Journal of Genetics 75(1): 19–25.
Relevant Websites http://authors.library.caltech.edu– History of Recent Science and Technology: Perspectives on Molecular Evolution – Fitch and the Heretic Kimura.