Barbara McClintock

For the illustrator named Barbara McClintock see Barbara McClintock (illustrator).

Cold Spring Harbor

After her year-long appointment McClintock was offered a full-time research position at Cold Spring Harbor. She was very productive and continued her work with the breakage-fusion-bridge cycle, using it as a substitute for X-rays as a tool for mapping new genes. In 1944 she undertook a cytogenetic analysis of Neurospora crassa at the suggestion of George Beadle who had used the fungus to demonstrate the one gene?one enzyme relationship. He invited her to Stanford to undertake the study. She successfully described the number of chromosomes, or karyotype, of N. crassa and also described the entire life cycle of the species. N. crassa has since become a model species for classical genetic analysis.

Related Topics:
Neurospora crassa - Stanford - Karyotype - Model species

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During this period in recognition of her prominence in the field of genetics McClintock was elected to the National Academy of Sciences in 1944, she was the third woman to be elected to the Academy. And in 1945 she became the first woman president of the Genetics Society of America.

Related Topics:
National Academy of Sciences - Genetics Society of America

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Discovery of controlling elements

In the summer of 1944 at Cold Spring Harbor, McClintock began systematic studies on the mechanisms of the mosaic color patterns of maize seed and the unstable inheritance of this mosaicism. She identified two new dominant and interacting genetic loci that she named Dissociator (Ds) and Activator (Ac). Dissociator did not just dissociate, or break, the chromosome; it also turned out to have a variety of effects on neighboring genes, but only when Activator was also present. In early 1948, she made the surprising discovery that both Dissociator and Activator could transpose, or change position on the chromosome.

Related Topics:
Mosaic - Inheritance - Dominant

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She observed the effects of Ac/Ds in the changing patterns of coloration in maize kernels over generations of controlled crosses, and was able to describe the relationship between the two loci through careful microscopic analysis. She concluded that Ac controlled the transposition of the Ds from chromosome 9, and that the movement of Ds was accompanied by breakage of the chromosome. When Ds moved the aleurone-color gene was released from the suppressing effect of the Ds and transformed into the active form, which initiated the pigment synthesis in cells. The Ds transposition in different cells was random, which caused the color mosaicism, with the size of the colored spot on the seed being determined by stage of the seed development when the dissociation occurred. McClintock found that the instability was determined by the number of Ac copies in the cell.

Related Topics:
Loci - Aleurone

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Between 1948 and 1950, she developed a theory by which these mobile elements regulated the genes by inhibiting or modulating their action. She referred to Dissociator and Activator as "controlling units" — later, as "controlling elements" — in order to distinguish them from genes. She also hypothesized that gene regulation could explain how complex multicellular organisms, made of cells with identical genomes could have cells that are functionally different. McClintock's discovery challenged the concept of the genome as a static set of instructions passed between generations. She published a paper on her results in 1950 and in summer 1951, she reported on her work on gene mutability in maize at the annual symposium at Cold Spring Harbor.

Related Topics:
Gene regulation - Genome

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Her work on controlling elements was conceptually difficult and was not immediately accepted by her contemporaries; she described the reception of her research as ranging from perplexed to hostile. Regardless, McClintock continued to develop her ideas on controlling elements and undertook numerous lecture tours to universities throughout the 1950s to speak about her work. She continued to work on the problem and identified a new element she called Supressor-mutator or Spm which although similar to Ac/Ds displayed more complex behavior, and were later shown to be the first described interaction of a DNA binding protein and its DNA binding site. McClintock knew she had veered outside the scientific mainstream and she stopped publishing accounts of her research on the subject of controlling elements in 1953.

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The origins of maize

In 1957 McClintock received funding from the National Science Foundation, and the Rockefeller Foundation sponsored McClintock to commence research on maize in South America. She was interested in studying maize evolution, and her work in South America would allow her to work on a large scale. McClintock explored the chromosomal, morphological, and evolutionary characteristics of different races of maize. From 1962 she supervised four scientists working on South American maize at the North Carolina State University in Raleigh. Two of these Rockefeller fellows, Almeiro Blumenschein and Angel Kato, continued their research on South American races of maize well into the 1970s. In 1981, Blumenschein, Kato, and McClintock published The Chromosomal Constitution of Races of Maize, it is considered a landmark study that contributed significantly to the fields of evolutionary botany, ethnobotany, and paleobotany.

Related Topics:
National Science Foundation - Rockefeller Foundation - South America - Evolution - Races - Almeiro Blumenschein - Angel Kato - Ethnobotany - Paleobotany

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Rediscovery of McClintock's controlling elements

McClintock officially retired from her position at the Carnegie Institution in 1967, however she chose to stay on in the Cold Spring Laboratory as scientist emerita. When she retired she was awarded the Cold Spring Harbor Distinguished Service Award. Following her retirement she worked with graduate students and colleagues who appreciated her work; she had stopped publishing detailed accounts of her work on controlling elements in 1953, and in 1973 she wrote "Over the years I have found that it is difficult if not impossible to bring to consciousness of another person the nature of his tacit assumptions when, by some special experiences, I have been made aware of them. This became painfully evident to me in my attempts during the 1950s to convince geneticists that the action of genes had to be and was controlled. It is now equally painful to recognize the fixity of assumptions that many persons hold on the nature of controlling elements in maize and the manners of their operation. One must await the right time for conceptual change." {{ref|1973letter}}

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The importance of McClintock's work only came to light in the late 1960s, when the work of French geneticists Francois Jacob and Jacques Monod described genetic regulation of the lac operon, a concept she had suggested in 1951. Her work on controlling elements was recognized following the discovery of transposition in bacteria and yeast in the early 1970s. Over this period molecular biology had developed significant new technology and scientists were able to show the molecular basis for transposition.

Related Topics:
Francois Jacob - Jacques Monod - ''lac'' operon

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In the 1970s Ac and Ds were cloned, and were shown to be Class II transposons. Ac is a complete transposon that can produce a functional transposase which is required for the element to move within the genome. The Ds element has a mutations in its transposase gene, which means that it cannot move without another source of transposase, thus as McClintock observed Ds cannot move when Ac is not present. Spm has also been characterized as a transposon. Research has also shown that transposons typically don't move unless the cell is placed under stress, like irradiation or the breakage, fusion, and bridge cycle, and thus their activation during stress can serve as a source of genetic variation for evolution. McClintock understood the role of transposons in evolution and genome change well before other researchers grasped the concept. Today Ac/Ds is widely used as a tool in plant biology to generate mutant plants to use for the characterization of gene function.

Related Topics:
Cloned - Class II transposons - Transposase

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