Concept


Thomas Hunt Morgan's concept of genes as beads along the length of a chromosome changed little through the first half of the 20th century. Genes were seen as inviolate objects with fixed positions on the chromosomes. However, in the 1950s, Barbara McClintock showed that certain DNA fragments, termed transposons, can be activated to transpose ("jump") from one position on a chromosome to another. She hypothesized that transposition provides a means to rapidly reorganize genes in response to environmental stress. McClintock's work was remarkable, not only for the fact that it flew in the face of prevailing dogma, but also because it was based entirely on observation of chromosomes and genetic crosses. Confirmation of her ideas had to await the discovery of the modern tools of DNA analysis. This work paved the way for the modern concept of chromosomes as dynamic, changing structures.

Animation


Hello, I'm Barbara McClintock. Ever since graduate school I had been interested in corn. I tried to correlate chromosome behavior with the results of breeding experiments in corn (maize). I spent most of my scientific career focusing on the short arm of chromosome 9, where, as a graduate student, I observed a characteristic bump or "knob." In the '30s, Harriet Creighton and I followed the transfer of this knob between two chromosomes during formation of sex cells. This chromosome "mixing" exactly paralleled the mixing of visible traits in the offspring. This was the first direct demonstration of the physical basis of genetic "crossing over," which had been discovered two decades earlier by Thomas Hunt Morgan?s group. Crossing over in corn works the same way as it does in Morgan's fruit flies. Harriet and I tracked the inheritance of the knob and 4 traits on chromosome 9. Crossover events are more frequent between genes that are further apart like C and Yg... ... and less frequent between genes that are closer together like C and Sh. Using crossover frequencies, we figured out the order of the genes on the chromosome and the relative distance between the genes. When I looked at a cell, it was like I was part of the system. The more I looked, the bigger the chromosomes got, and I was even able to see the integral parts of the chromosomes. I felt like I was right there with them. I was able to identify chromosomal abnormalities. I could see chromosome fragments left over from broken chromosomes. I also figured out that "ring" chromosomes are actually chromosomal fragments whose ends fused to form a ring structure. I tracked the inheritance of these rings through mitotis and found that they can be lost. So, different populations of corn cells can express different genes depending on when they keep or lose the ring chromosome. I suspected that some kind of chromosome breaking ? or dissociation ? on the short arm of chromosome 9 caused purple-spotted kernels. I tracked the source of instability to a locus I called Dissociator (Ds), which was under the control of a second locus called Activator (Ac) on the long arm. Let me explain. Although you surely are familiar with white or yellow corn, certain types of corn naturally produce dark purple or blue kernels! So called "blue corn" tortillas are made from such kernels. The Colored (C) gene on the short arm of chromosome 9 controls the production of one of the purple pigments. The Colored gene is passed on as cells divide to produce the kernel. However, the purple color only develops in the "skin" of the kernel. I reasoned that colorless kernels resulted when a copy of the Ds element inserts and disables the Colored gene. Then, all of the cells in the developing kernel inherit a nonfunctional gene, which cannot produce the purple pigment. This results in a white or yellow kernel. Now imagine what happens if Ds is destabilized in the presence of Ac. Kernel development begins with Colored gene disabled by an inserted Ds element. However, at some point a transposition event occurs in a single cell. Under control of Ac, Ds "jumps" out of the Colored gene and reinserts elsewhere on Chromosome 9. This results in a functional Colored gene, which is passed on to a large group (or clone) of daughter cells. A second Ds transposition occurs later in development, resulting in a smaller group of daughter cells with a restored Colored gene. So, the number and size of spots indicates the frequency and timing of transposition events during kernel development. Early transpositions produce fewer and larger pigmented spots, while frequent events later in development produce a finely speckled pattern. I believed that transposition had a more important function than merely to turn color genes on and off. In 1983, at my Nobel Prize lecture, I emphasized that transposition can provide a means to rapidly reorganize the genome in response to environmental stress. In this sense, mutations produced by transposition are a source of variation to drive the process of evolution.

Gallery


Barbara McClintock as a Cornell coed, 1923.
Barbara McClintock as a graduate student at Cornell, 1929. (L-R standing) Charles Burnham, Marcus Rhoades, Rollins Emerson, and Barbara McClintock. George Beadle is kneeling by the dog.
Barbara McClintock at Cold Spring Harbor Laboratory, 1951.
Barbara McClintock and Harriet Creighton at a meeting at Cold Spring Harbor Laboratory.
Barbara McClintock working in the cornfield at Cold Spring Harbor Laboratory.
Barbara McClintock on a collection trip to Chapingo, Mexico in 1959.
Barbara McClintock teaching a 1981 plant genetics course at Cold Spring Harbor Laboratory.
Barbara McClintock at the opening of the McClintock building at Cold Spring Harbor Laboratory.
Barbara McClintock at the Nobel ceremonies, 1983.

Audio/Video


Audio Glossary

Gene, Insertion, Linkage

Video Interviews

Nathaniel Comfort

Nathaniel Comfort teaches history of science and medicine at George Washington University. In 2001, he published The Tangled Field, a biographical study of McClintock's life, thought, and impact.

Clip 1 (00:54)
McClintock's contributions to corn genetics.

Clip 2 (00:58)
Comments on McClintock's 1931 paper.

Clip 3 (01:52)
How was McClintock able to do what she did?

Clip 4 (00:43)
Comments on how McClintock used the breakage fusion bridge cycle to look for new mutations.

Clip 5 (1:32)
What did McClintock think about the dissociator and activator genes?

Clip 6 (1:33)
Why did McClintock stay at Cold Spring Harbor Laboratory?

Biography


 

Barbara McClintock did pioneer work in plant genetics. She received the Nobel Prize for Physiology or Medicine in 1983.

BARBARA MCCLINTOCK (1902-1992)

Barbara McClintock was born in Hartford, Connecticut. Her father was an army doctor and her mother was a piano teacher. McClintock was an active child and enjoyed many sports like volleyball, skating, and swimming. She had a passion for information, and in a time when a woman's career was a successful marriage, McClintock was determined to go to college. In 1918, she enrolled in Cornell University, the College of Agriculture.

Under the social and intellectual background of college, McClintock blossomed into a popular coed. By the time she finished her undergraduate credits, she found herself in graduate school in the new field of cytology. As a paid assistant in her second year of graduate work, she improved on a method that her employer was using and was able to identify maize chromosomes. It was a problem he had been working on for years and she effectively scooped her own boss.

When she finished her Ph.D. in 1927, McClintock knew that her next step was to map corn chromosomes in linkage groups like T. H. Morgan's group was doing for Drosophila. To do this work, McClintock stayed at Cornell as an instructor. She met fellow graduate students Marcus Rhoades and George Beadle who became lifetime friends as well as colleagues. McClintock helped Beadle sort out the Neurospora chromosomes. Beadle, with Edward Tatum, built on this work and developed the "one gene, one enzyme" theory using Neurospora.

In 1929, McClintock met Harriet Creighton, a new graduate student at Cornell. The two of them became friends and worked together to show that chromosomal crossovers occur in corn chromosomes.

In 1931, supported by a fellowship from the National Research Council, McClintock started splitting her time between the University of Missouri and Cornell. She began investigating the effects of X-rays on corn chromosomes, which led to her discovery of translocations, inversions, deletions and ring chromosomes in corn.

After a depressing and disappointing sojourn in Germany in 1933, McClintock returned to Cornell and with some support from the Rockefeller Foundation managed to stay for almost three years. In 1936, she was finally offered a faculty position at the University of Missouri. McClintock was assistant professor at the University for five years until she realized that her independent and "maverick" ways were not in keeping with the University's idea of a "lady" scientist. Knowing that she would never be promoted, McClintock left in 1941.

Marcus Rhoades, who was at Columbia University, and Milislav Demerec, a Drosophila scientist at Cold Spring Harbor, invited her to Cold Spring Harbor Laboratory for the summer. Rhoades was growing his corn there, and Demerec knew and respected McClintock as a scientist. McClintock stayed for the summer and late into the fall. When Demerec became the Director of the Department of Genetics of the Carnegie Institution of Washington at Cold Spring Harbor, he offered McClintock a position. Undecided at first, McClintock finally accepted the position in 1942. It was at Cold Spring Harbor that McClintock figured out the process of transposition in corn chromosomes. For this and her other work, McClintock was awarded an unshared Nobel Prize for Physiology or Medicine in 1983.

Although many people recognized McClintock's genius, she herself admitted that sometimes it was difficult for her to express her ideas. Her work on transposition in corn chromosomes was fairly well-known but little understood until the molecular basis for transposition was shown in 1970s. McClintock was frustrated by other people's lack of understanding and acceptance of an idea that was so clear and reasonable to her.

McClintock was a research investigator at Cold Spring Harbor until her death in 1992. She enjoyed playing tennis. Each fall, she was often seen on the Cold Spring Harbor grounds collecting black walnuts for use in baked goods that she gave to a favored few of her colleagues. In addition to her brilliance as a geneticist, many people remember her quick wit and her sense for fun. She was dedicated to, and passionate about, her work, and was happiest in the cornfield or in her laboratory.

Factoid

Links


 

Links

Transposable Genetic Elements

From North Dakota State University's Phil McClean, this web site has summaries of transposable elements found in different organisms. Dr. McClean teaches genetics at North Dakota State University.

Jumping Jordan Gene

A news brief appearing in Access Excellence's web site about how researchers named a transposon after Michael Jordan, the basketball star.

Bibliography

  • Fedoroff, N., and Botstein, D., (ed.), 1992, The Dynamic Genome, Cold Spring Harbor Laboratory Press, New York.

  • Keller, E. F., 1983, A Feeling for the Organism: The Life and Work of Barbara McClintock, W.H. Freeman and Company, New York.

  • McClintock, B., 1931, The Order of the Genes C, Sh and Wx in Zea mays with Reference to a Cytologically Known Point in the Chromosome, Botany, 17: 485-491.

  • McClintock, B., and Creighton, H.B., 1931, A Correlation of Cytological and Genetical Crossing-over in Zea mays, Botany, 17: 492-497.

  • McClintock, B., 1932, A Correlation of Ring-shaped Chromosomes with Variegation in Zea mays, Proc. Natl. Acad. Sci. U.S.A., 18: 677-681.

  • McClintock, B., 1965, The Control of Gene Action in Maize, Genetic Control of Differentiation, Brookhaven Symposia in Biology, 18: 162-183.

  • McClintock, B., 1984, The Significance of Responses of the Genome to Challenge, Science, 226: 792-801.

Glossary


Gene - The functional and physical unit of heredity passed from parent to offpsring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.
Insertion - A type of chromosomal abnormality in which a DNA sequence is inserted into a gene, disrupting the normal structure and function of that gene.
Linkage - The association of genes and/or markers that lie near each other on a chromosome. Linked genes and markers tend to be inherited together.

Children resemble their parents.
Genes come in pairs.
Genes don't blend.
Some genes are dominant.
Genetic inheritance follows rules.
Genes are real things.
All cells arise from pre-existing cells.
Sex cells have one set of chromosomes; body cells have two.
Specialized chromosomes determine gender.
Chromosomes carry genes.
Genes get shuffled when chromosomes exchange pieces.
Evolution begins with the inheritance of gene variation.
Mendelian laws apply to human beings.
Mendelian genetics cannot fully explain human health and behavior.
DNA and proteins are the molecules of the cell nucleus.
One gene makes one protein.
A gene is made of DNA.
Bacteria and viruses have DNA too.
The DNA molecule is shaped like a twisted ladder.
A half DNA ladder is a template for copying the whole.
RNA is an intermediary between DNA and protein.
DNA words are three letters long.
A gene is a discrete sequence of DNA nucleotides.
The RNA message is sometimes edited.
Some viruses store genetic information in RNA.
RNA was the first genetic molecule.
Mutations are changes in genetic information.
Some types of mutations are automatically repaired.
A chromosome is a package for DNA.
Higher cells incorporate an ancient chromosome.
Some DNA does not encode protein.
Genes can be turned on and off.
Genes can be moved between species.
DNA responds to signals from outside the cell.
Different genes are active in different kinds of cells.
Master genes control basic body plans.
Development balances cell growth and death.
A genome is an entire set of genes.
Living things share common genes.
DNA is only the starting point for understanding human biology.
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