In 1951, two years before the double-helical structure of DNA was discovered, Barbara McClintock gave a lecture on her newest research into maize genetics, which revealed something truly surprising—certain genes were able to jump from one region of the genome to another. These jumping genes appeared to have a pronounced effect on the regions where they landed, disrupting and inactivating nearby genes. In maize (i.e., corn), these effects were easily visualized as changes in the color pattern of kernels over generations. Despite compelling evidence, McClintock’s lecture was met with confusion and open hostility from the scientific community because it conflicted with the predominant understanding that genes were linear and only occasionally changed through irreversible mutations. McClintock wasn’t discouraged though and continued studying this phenomenon. In the 60s and 70s, researchers began discovering that these jumping genes, or transposons as they came to be known, were everywhere—including in 50% of the human genome. And in 1983, McClintock was awarded the Nobel Prize in Physiology or Medicine for the “discovery of ‘mobile genetic elements.’”
McClintock began her scientific career at Cornell University’s College of Agriculture where she earned her BSc in 1923 and her PhD in botany in 1927. She then worked at Cornell as an instructor until 1936. While at Cornell, McClintock developed her own staining technique for looking at the DNA in maize, allowing her to distinguish the 10 different maize chromosomes and link hereditary changes with their genetic causes. In 1931, McClintock and her graduate student, Harriet Creighton, were the first to demonstrate genetic recombination, the exchange of genetic information between chromosomes before they are split up for reproduction. This discovery earned McClintock acclaim in the scientific community. In 1944, she was elected to the National Academy of Sciences, and in 1945, she was elected as the first woman president of the Genetics Society of America. In 1941, eager to dedicate more of her time to research, McClintock left her teaching position at Cornell and took a research position at the Cold Spring Harbor Laboratory, where she would go on to make discoveries that would later earn her the Nobel Prize.
During her research at Cold Spring Harbor, while investigating the genetic factors responsible for the variations in maize kernel color, McClintock discovered irregular chromosome breaks in chromosome 9. She found that the cause of these breaks was the transposition of a mobile genetic element from one location in the chromosome to another. Insertion of this element, which McClintock named the “dissociation” or Ds element, disrupted the expression of nearby genes. With further investigation, McClintock found that transposition of Ds was dependent on the presence of another element called “activator” or Ac, which controlled and modulated Ds transposition. She identified several different forms of Ds and Ac, each causing different levels of gene inactivation and resulting in different kernel color patterns.
When McClintock presented her research in 1951, she was met with heavy skepticism from the scientific community. The common understanding of genetics at the time was that genes were arranged linearly and statically and, when mutations occurred, they were permanent changes in the genetic sequence. But McClintock was not deterred. “I just knew I was right,” she said, “anybody who had had that evidence thrown at them with such abandon couldn’t help but come to the conclusions I did about it.” Continuing her research into mobile elements, McClintock discovered a new mobile element, known as Suppressor-Mutator or Spm, which could switch back and forth between an inactive and active form depending on the area of the plant and its developmental stage. This observation was some of the first evidence of epigenetic methylation, where non-genetic factors can influence gene expression.
While the scientific community was slow to accept the idea that certain genes may be able to jump throughout a chromosome, in the 1960s, additional research revealed other cases of transposition in bacteriophages (viruses that infect bacteria), bacteria, and fruit flies. In bacteria, transposition is an integral element in how antibiotic resistance gets conveyed from one bacterium to another. In the 1980s, researchers were able to isolate the Ac and Ds genes that McClintock discovered, and they found that these transposons encoded for the enzyme they needed to cut and paste themselves, known as transposase. Today, we know that almost 50% of the human genome is composed of transposons, and these jumping genes have been influential drivers of evolutionary change. Transposon insertions that were beneficial or neutral in the past were carried on into future generations, but over time, the capacity for these genes to continue jumping without causing negative outcomes diminished. As a result, 99% of the transposons in the human genome are currently static.
LINE-1 is an example of one of the still-active transposons in humans. Unlike the Ds/Ac system McClintock discovered in maize, LINE-1 is a retrotransposon—meaning it gets copied as RNA, and then reverse transcriptase enzymes use that RNA as a template to insert that gene somewhere else. LINE-1 has been copied and pasted so many times that almost 18% of the human genome is just copies of this one transposon. Often LINE-1 insertions are harmless, but occasionally, the transposon can land in the middle of an important gene, resulting in negative health consequences. LINE-1 insertion has been linked to many health conditions, including some cancers, hemophilia, and autoimmune responses.
Even after her retirement in 1967, McClintock continued working at Cold Spring Harbor as a Distinguished Service Member and attended seminars there until her death in 1992.
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