Biohistory Jyournal, Spring, 2004

Scientist Library: Index > Continuing to question the essence

Continuing to question the essence

Prof. Takashi Miyata, Graduate School of Science, Kyoto University (Now JT Biohistory Research Hall)

photograph by Seiya Kawamoto

I liked math as a child and was absorbed in the study of theoretical physics during my university days. As time went on, I advanced to biophysics. Before I knew it, I wound up headed for the most complex area of the life phenomenon, which is evolution. I was a pioneer in the new field of molecular evolution. I continually question to learn about the essence of evolution.

Quantum biology     When I entered graduate school, an exceptional subatomic physicist turned his attention to biophysics and began the study of quantum biology to understand the phenomenon of life from the perspective of quantum mechanics. I also turned my complete attention from subatomic research to biophysics. I started work at Waseda University's biophysics lab and began research into the electronic state of DNA using a computer. There were some struggles, but it was interesting because it was a new field.     During the course of my research, however, I began to have doubts about quantum physics. I began to suspect that the phenomenon of life might be apprehended not through electronics, but through the molecules of enzyme and DNA. In 1973, Professor Hirotsugu Matsuda began a new course in mathematical biology, and he invited me to join. Mathematical biology is the attempt to understand the phenomenon of life using mathematics. I had the idea of conducting research into evolution from the molecular level (DNA), so I transferred to Kyushu University.  The study of molecular evolution     I was convinced that the study of the genome sequence in DNA was coming, so through trial and error, I worked out a program for the analysis of that sequence. In 1976, Sanger determined the fuzzy sequence of j x 174. In that sequence, he discovered an overlap in the genes transcribed with one sequence in two different reading frames. I immediately tried to analyze that with the program. When I did so, I found that this sequence, which I had thought resembled an ordinary genetic sequence in that it was incapable of change, could actually change quite substantially. (These findings were published in Nature in 1978.)     This data supported the idea that of the neutral evolution of DNA, so when the thesis appeared, I immediately received a call from Dr. Motoo Kimura, a proponent of the neutral theory. I had not quoted his neutral theory from my list of sources. I came from the field of physics, so I didn't know anything about it. Really (laugh). But Dr. Kimura thanked me for my analysis based on neutrality and sent me a copy of his thesis. Perhaps he meant to say that I actually had quoted from it.  Verification of the neutral theory     The American geneticist Dr. Crow visited me in 1980, and he told me about a pseudo-gene that resembled the alpha globin gene, but for which transcription stopped part way through. I immediately thought this would verify the neutral theory and asked if that gene had a function. Crow answered that it probably didn't. If it had no function, its evolution speed would be the maximum in the neutral theory. Considered from the perspective of natural selection, the evolution speed should be 0--if there is no function, selection doesn't come into play. In other words, the entirely opposite result would be expected depending on which theory was adopted. I made the calculations right away, and wrote a thesis in one week. The result was strong data supporting the neutral theory, with evolution speed at the maximum.     Later, I developed the homology search method, presented the male-determining evolution theory, in which the male of the species determines evolution, and fixed the evolutionary location of old bacteria by using gene duplication. I left behind very significant research into the evolutionary mechanism of molecules and molecular genealogy, putting an end to a controversy that had lasted 10 years.

The field of theoretical physics which I first came into contact with university. I well recall studying this text with rapt attention.  At an academic conference in Hokkaido while a student at Kyushu University. Left: Takashi Gojobori (National Institute of Genetics: professor) / Center: Miyata / Right: Teruo Yasunaga (Osaka University professor)  With my first student, Gojobori. Left: Miyata / Right: Prof. Gojobori

A letter from Dr. Kimura, who wrote to me occasionally / The book about the neutral theory, with his signature and comment

Verification of the neutral theory     The American geneticist Dr. Crow visited me in 1980, and he told me about a pseudo-gene that resembled the alpha globin gene, but for which transcription stopped part way through. I immediately thought this would verify the neutral theory and asked if that gene had a function. Crow answered that it probably didn't. If it had no function, its evolution speed would be the maximum in the neutral theory. Considered from the perspective of natural selection, the evolution speed should be 0--if there is no function, selection doesn't come into play. In other words, the entirely opposite result would be expected depending on which theory was adopted. I made the calculations right away, and wrote a thesis in one week. The result was strong data supporting the neutral theory, with evolution speed at the maximum.     Later, I developed the homology search method, presented the male-determining evolution theory, in which the male of the species determines evolution, and fixed the evolutionary location of old bacteria by using gene duplication. I left behind very significant research into the evolutionary mechanism of molecules and molecular genealogy, putting an end to a controversy that had lasted 10 years.

An enlargement	Stirring up debate The male-determining evolution theory, 1987     There is a difference in the mutation rate among chromosomes because there is a difference in the number of divisions of the sperm and the egg. When the male has heterogeneous chromosomes (females: XX, males: XY) as do mammals, the mutation rate is largest in Y chromosomes, followed by autosomal chromosomes, and then X chromosomes. In birds, however, this is reversed, because females have heterogeneous chromosomes (females: ZW, males: ZZ). The mutation rate is the opposite of that in mammals. The theory was substantiated by the results of a Swedish group working with birds, which were announced in 1997.

Biodiversity and the evolution of genes     I moved to Kyoto University in 1990 and resolved to devote myself to the ultimate question--how to connect evolution at the level of form and at the molecular level. They built a laboratory where I could conduct experiments, and I began to work on the problem of the immense genetic diversification that began with the diversification of forms after the famous Cambrian explosion. The results were quite different from what I had anticipated. Unquestionably, there had been an explosive increase in genes, but that had been long before the Cambrian explosion. There was almost no diversification in genes at the time of the Cambrian explosion.     To consider the molecular mechanism of the Cambrian explosion, one had to think from the perspective of somehow achieving a diversity of form using existing genes, and not from the perspective of creating new genes. This is called the "soft model" of diversification. In the future, I am thinking of conducting trials and experiments with this model, and examining a simulation of the molecular mechanism that may well be the model itself.     An important aspect of working on a major problem is framing the questions, and that is a task I relish. I get very excited when I can devise good questions. My work at Kyoto University will end this year, and in the future, I will lavish my time on the relationship between the universal nature of human beings and evolution.     I thought that since I had come to Kyoto, I would get involved with something associated with Kyoto, so I began to study how to make Noh masks. Actually, I do exactly as I am told and imitate the model perfectly.

When I received the Kimura Motoo Prize  The people in the second photo 30 years later. Left: Prof. Gojobori / Center: Miyata / Right: Prof. Yasunaga  With Dr. Svante Paabo, who had come for a visit, in front of the Ginkaku-ji Temple.

Takashi Miyata 1940: Born in Katsushika Ward, Tokyo 1964: Graduated with a degree in Applied Physics from the School of Science and Engineering, Waseda University 1969: Completed the work for a doctorate in Applied Physics, the Graduate School of Science and Engineering, Waseda University, and was awarded a Ph.D. in Science 1969: Named assistant in the Department of Physics, School of Science, Nagoya University 1973: Named assistant professor, Department of Biology, School of Science, Kyushu University 1990: Named professor, Department of Biophysics, Division of Biological Sciences, Faculty of Science, Kyoto University 1995: Named professor, Department of Biophysics, Division of Biological Sciences, Graduate School of Science, Kyoto University 2004: JT Biohistory Reseach Hall

-Awards- 1996: Kihara Award, The Genetics Society of Japan 2002: Kimura Motoo Memorial Academic Award

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