Susumu Ohno (1928–2000)

Susumu Ohno studied chromosome structure and evolution during the twentieth century in the United States. Ohno was one of the first researchers to propose that the Barr body, a mass of genetic material within female mammalian cells, was a condensed X-chromosome. Ohno also developed a theory that gene duplication, when specific regions of a chromosome become multiplied, is a primary driver of evolution, with natural selection playing a secondary role. He theorized that gene duplication allows one copy of the original gene to remain and perform its normal function while a second copy of the gene can mutate and undergo natural selection, leading to diversification of life. Later in his career, Ohno composed music based on DNA sequences. As of 2025, researchers continue to debate Ohno’s theory of gene duplication. Through his research, Ohno introduced a new perspective on the driving forces of evolution, which advanced researchers’ understanding of chromosomal evolution and genetic diversity.

1. Early Life and Education
2. Early Career and Research on the X-chromosome
3. Ohno’s Law
4. Research on Gene Duplication and Evolution
5. Research on Sex Determination with HY Antigen
6. Creation of DNA Music
7. Awards and Legacy

Early Life and Education

Ohno was born on 1 February 1928, in Seoul, South Korea, which was then under Japanese rule. Ohno came from a well-educated family and was the second of five children. His father, whose name is not recorded in published obituaries, was the minister of education of the Japanese Viceroyship of Korea, and both of his grandfathers held high ranking scholarly positions as well. According to a biography on Ohno by Ernest Beutler, a physician and biological researcher who knew Ohno personally, Ohno’s family held unusually liberal values compared to Japanese society regarding education as well as race by viewing all races as equal. The local public school did not allow Ohno to attend due to the family’s liberal ideas, so he attended a private school and received tutoring in Chinese language and history. The Ohno family owned a few horses, and Ohno began riding at a young age. Beutler mentions in his biography of Ohno that Ohno’s passion for horses continued throughout his lifetime and influenced his career choice.

In his biography of Ohno, Beutler explains that Ohno developed a curiosity about the relationship between a horse’s capabilities and the horse’s genetics, which impacted Ohno’s educational choices. As a result, Ohno pursued a degree in veterinary medicine at the Tokyo University of Agriculture and Technology in Tokyo, Japan, and graduated with his degree in 1949. Around the same time, Ohno met Midori Aoyama, and they married in 1951. Eventually, the couple had two sons and one daughter.

In the summer of 1952, Ohno went to the University of California in Los Angeles, California, or UCLA, as a visiting scholar. At the time of his arrival, the City of Hope Medical Center in Duarte, California, approximately fifty miles outside of UCLA, had begun a new research department. The City of Hope is a research center focused on cancer, diabetes, and other chronic diseases. In 1952, Riojun Kinosita, a researcher who studied cancer, became the first director at the City of Hope’s newly developed research department and recruited Ohno to work with him as a research associate that same year.

Before beginning his research at the City of Hope’s research center, Ohno went back to Japan to finish his graduate studies and received his PhD in immunology from Hokkaido University, in Hokkaido, Japan, in 1953. His dissertation focused on the role of immune cells in antibody production. After completing his graduate studies, he moved back to California with his wife in 1953.

Early Career and Research on the X-chromosome

After completing his graduate studies, Ohno studied how bone marrow gives rise to blood cells at the City of Hope’s research center. He developed cinematographic, or motion-picture, techniques for studying living bone marrow. According to Beutler, Ohno’s initial work established him as a highly skilled experimentalist, and those skills allowed him to experiment later with genetic mechanisms.

In the mid-1950s, Ohno began studying X-chromosomes and identified that the two X-chromosomes in female cells display different structures. Ohno, along with Kinosita and William Kaplan, another researcher at the City of Hope, began their research on the behavior of the X-chromosome in rat liver cells. According to Beutler’s biography, the team identified that what scientists previously believed to be two X-chromosomes packed closely together in female cells under a microscope was actually one X-chromosome that was denser, or more tightly packed. They found that the denser chromosome was heterochromatin, which is a tightly packed form of DNA with a distinct structure compared to the other X-chromosome. The team realized that the singular, condensed X-chromosome was close to the size of the small sex chromatin structure in a female rat cell, previously recognized by scientists as the Barr Body. In their 1959 article entitled “Formation of the Sex Chromatin by a Single X-Chromosome in Liver Cells of Rattus Norvegicus,” Ohno and his team concluded that a Barr Body is equivalent to a condensed X-chromosome. The paper did not provide an explanation for the mechanism on how a chromosome becomes a condensed Barr Body in rat liver cells, but the research team did theorize that the X-chromosome inherited from the father becomes the Barr body structure during a phase in cell duplication.

Ohno’s research on the Barr Body aided Mary Lyon, a researcher who studied X-chromosomes in Harwell, United Kingdom, in the development of her Lyonization hypothesis, which she published in 1961 . The Lyonization hypothesis states that the condensed X-chromosome in female mammalian cells is genetically inactive, meaning cells do not read and transcribe the information on that chromosome. Following Ohno and his colleagues’ paper, scientists knew that a condensed structure existed in female mammalian cells known as heterochromatin, but they did not know that the heterochromatin was completely inactive in mammals. Through her research, Lyon concluded that one X-chromosome, and therefore the Barr Body, in females is inactive.

After publishing his research on the structure of the X-chromosome, in 1966, Ohno received a promotion to chairman of the City of Hope Division of Biology, a position he held until 1981.

Ohno’s Law

In 1967, Ohno theorized that all mammalian species have inherited the X-chromosome from a common ancestor, causing all mammalian species to share the same X-linked genes, a theory that scientists now refer to as Ohno’s Law. Ohno observed that even though the number of chromosomes varied across species, the overall X autosome ratio, or ratio between the number of X-chromosomes and the number of sets of autosomes, was roughly the same. Autosomes are chromosome pairs that contain all the genetic code for an individual except the traits related to sex. Ohno published his theory in his 1967 book Sex Chromosomes and Sex-linked Genes. In his book, Ohno explained that because the X autosome ratio remains consistent across species, mammalian species conserve the fundamental organization and inheritance patterns of X-linked genes through evolution. He wrote that, because the X-chromosome is present in both males and females, the importance and location of genes on the X-chromosome have been similar across many species through evolution. So, if a gene is X-linked in one species, it's likely to be X-linked in another species because the basic structure of the X chromosome and the way genes on it are inherited has been maintained through evolutionary history. Since its creation, Ohno’s law has enabled scientists to find and study X-linked genes and diseases across species, such as hemophilia, a rare disorder where blood does not clot properly.

Research on Gene Duplication and Evolution

Throughout the 1960s, Ohno theorized that gene duplication is the primary driver of genetic diversity in evolution, with natural selection playing a secondary role. He published his findings in his 1970 book titled Evolution by Gene Duplication. Gene duplication is the process of organisms duplicating regions of a chromosome so that there are multiply copies of it. In his book, Ohno suggests that natural selection is not the only major process that drives evolution. If it was, he claims that the jump from unicellular to multicellular organisms would have been practically impossible because the jump to multicellularity would require multiple genes to evolve together. Thus, relying on natural selection alone to make all the genetic changes needed for multicellularity would be improbable.

Ohno proposed that gene duplication creates redundancy in DNA, allowing one copy to remain unaltered, while the other, redundant gene is free to mutate to create genetic diversity. That meant that gene duplication could make entirely new genes with new functions. Prior to Ohno’s research, scientists knew that gene duplication occurred, but Ohno specifically linked gene duplication events to evolution. Ohno’s basic postulates from his 1970 book remain relevant, as of 2025.

In 1972, Ohno built on his gene duplication theory by suggesting that the noncoding sequences of human DNA represent genes that died off from older ancestors. Approximately ninety-nine percent of the human genome is noncoding sequences, meaning that they do not code for protein sequences, while the remaining one percent codes for proteins. In his 1972 article titled “So Much ‘Junk’ DNA in Our Genome,” Ohno proposed that the noncoding regions represented the remains of extinct genes, or genes from earlier evolutionary ancestors. He also popularized the term junk DNA to refer to the ninety-nine percent of DNA that is non protein coding. As of 2025, scientists know that non-coding DNA regions are not entirely without function.

Research on Sex Determination with HY Antigen

Ohno published his last monograph, Major Sex-determining Genes, in 1979, in which he presented the HY antigen as a primary sex-determining factor. An antigen is a foreign substance in the body that triggers an immune response. The HY is an antigen produced by genes on the Y-chromosome in males and related to immune system recognition, especially in transplant cases. is the process through which a fetus becomes biologically male or female. Ohno specifically theorized that the HY antigen triggered sex determination. Prior to Ohno’s work, scientists in the 1970s knew that the HY antigen is only present in male cells and that some antigens, such as the HY antigen, can also invoke immune responses. As of 2025, however, scientists know that the HY antigen alone does not induce the formation of the male sex organs known as the testes. Scientists view the SRY gene, not the HY antigen, as the critical sex-determining gene. The SRY is a gene on the Y-chromosome that produces a protein that causes a fetus to develop testes. Scientists view the SRY gene as the key initiator of male development whereas the HY antigen contributes to the maintenance of male sexual characteristics as well as immune system function.

Creation of DNA Music

During the latter part of his research career, Ohno created music based on DNA sequences. Ohno saw the repetitive patterns that existed in DNA from years of evolution and found it similar to human music compositions. Thus, he assigned specific notes to nucleotides and converted the DNA sequences to musical passages, which his wife performed on the piano. The couple created pieces based on various biological molecules. In 1986, he published his research on DNA music in the journal Immunogenetics. Ohno retired from his work and the City of Hope research institute in 1996. As of 2025, other musicians have recorded some of his musical pieces, which exist on YouTube.

Awards and Legacy

Ohno received many awards throughout his research career. In 1974, the American Academy of Arts and Sciences elected Ohno into the academy after careful reviews and an election process. In 1981, the National Academy of Sciences inducted Ohno for his research. Ohno also won the Japanese Human Genetics Society Prize and the Francis Amory Prize for Reproductive Biology of the American Academy of Arts and Sciences in 1981 for his contributions to those fields. In 1983, Ohno won the Kihara Prize of the Japanese Society of Genetics for outstanding research in genetics. In 1984, the University of Pennsylvania, in Philadelphia, Pennsylvania, presented Ohno with an honorary degree. In 1992, the Royal Danish Academy of Sciences and Letters inaugurated Ohno for his work. After his retirement, the Royal Danish Academy awarded Ohno with the Royal Danish Association of Science Research Prize, also known as the Inaugural Queen Margarethe Prize, in 1998. The Academy presents the prize once a year to a scientist who has made considerable contributions to their field.

Throughout his career, Ohno published over 350 papers in leading scientific journals. As of 2025, his book, Evolution by Gene Duplication, has over 9,400 citations, according to Google Scholar. Researchers continue to expand and test his ideas using newer, advanced equipment available to scientists. For example, in 2017, Yves Van de Peer, a researcher who studies gene duplication at Ghent University in Ghent, Belgium, and his team supported Ohno’s proposal that many species undergo gene duplication. The team looked through chromosomes of organisms of the same species at different evolutionary stages and found that many species evolved through duplicating their entire genome during long periods of external stress, resulting in organisms having duplicated genes. Most scientists also accept the ideas in Ohno’s initial book, Sex Chromosomes and Sex-Linked Genes, and researchers focusing on topics such as sex determination, evolution, genetic inheritance, or gene regulation have cited his book over 2,200 times. Overall, Ohno’s research combining genetics and evolution expanded the field of evolutionary biology by describing how diversity in evolution arises through gene redundancy and gene duplication events.

Ohno died on 13 January 2000 at the age of seventy-one due to lung cancer.

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