While in the 1930s it was suspected that chromosomes harbored genes, the pieces of genetic material that code the way we are, this has not been empirically proven. Many had tried, but no one had found visual evidence for the chromosome-gene relationship.
But Barbara McClintock arrived, and with her self-cultivated corn plants, she managed to prove it, even though many saw her as a simple botanist looking like a geneticist.
The figure of this researcher is that of a person who, due to her advancement for her time, was a misunderstanding. Below we will find out what its history has been a biography of Barbara McClintock, in which we will see why it was so important for the history of genetics.
Brief biography of Barbara McClintock
Barbara McClintock was an American scientist specializing in cytogenetics who won the Nobel Prize in Medicine or Physiology in 1983., being the seventh woman to receive such recognition.
His work accurately answered the most interesting question of the 1930s: what cellular structure are genes in? McClintock’s research, along with that of his doctoral student Harriet Creighton, has served to empirically show that genes are located on chromosomes. His work with corn plants provided for the first time a visual connection between certain inherited traits and their base in chromosomes.
His research also revealed that genes do not always occupy the same place on the chromosome. McClintock discovered gene transposition, which clashed with his day’s idea that genetic material was static. It was therefore a much more complex and flexible element than was assumed at the time, a dynamic structure capable of reorganizing itself.
Childhood and adolescence
Barbara McClintock was born in Hartford, Connecticut, United States on June 16, 1902. She was first registered as Eleanor, but the record was changed at four months to the name she was known by, Barbara. She was the third daughter of the marriage of Dr Thomas Henry McClintock and Sara Handy McClintock. He showed more closeness to his father than to his mother, and as an adult he pointed out that they had both been very supportive of him, even though his relationship with his mother had been rather cold.
From a young age, McClintock showed great independence, which she herself would describe as a great ability to be alone. From the age of three until he started school, McClintock lived with his uncles in Brooklyn, New York, to support his family financially while his father opened an office.
He graduated from high school at Erasmus Hall High School in Brooklyn. From an early age he showed an interest in science, so he decided to continue his studies at Cornell University. Her mother objected, not wanting her daughters to go to higher education, believing it would hurt their chances of getting married. In addition, the family experienced some financial problems that prevented them from paying for their children’s college education.
Fortunately, Barbara McClintock was able to attend Cornell School of Agriculture without having to pay tuition, and after graduating from high school was able to combine work in an employment office with self-taught training derived from the public library. Finally, thanks to the intervention of her father, she entered Cornell in 1919 where her success was not only academic but also social, being elected president of a student association in her first year.
Training and research at Cornell
McClintock began studying at the Cornell School of Agriculture in 1919, where he studied botany and obtained his Bachelor of Science (BSc) in 1923. His interest in genetics was awakened in 1921, when he attended the first year of this subject, under the direction of breeder and geneticist CB Hutchison. Due to McClintock’s keen interest, Hutchinson invited her to participate in a postgraduate genetics course in 1922. This will mark a before and after in McClintock’s career, focusing his vital efforts on deepening his genetics. .
Both studying for a degree and working as a professor of botany, McClintock he devoted himself to what was then the new field of corn cytogenetics. His research group consisted of plant breeders and cytologists, including Charles R. Burnham, Marcus Rhoades, George Wells Beadle, and Harriet Creighton.
The main goal of McClintock’s work at the time was to develop techniques to visualize and characterize corn chromosomes. He created a technique based on carmine staining to be able to see these chromosomes under light microscopy, showing for the first time the shape of the ten chromosomes in corn. By studying the morphology of these chromosomes, he was able to relate inherited traits in conjunction with chromosomal segments and confirm that the chromosomes harbor genes.
In 1930, Barbara McClintock was the first person to describe the intersections that occur between homologous chromosomes during meiosis. With his doctoral student Harriet Creighton, he showed in 1931 that there is a relationship between this meiotic chromosomal crossover and the recombination of hereditary traits. McClintock and Creighton observed that chromosomal recombination and the resulting phenotype resulted in the inheritance of a new trait.
During the summers of 1931 and 1932 he worked in Missouri with the prestigious geneticist Lewis Stadler, who showed him the use of X-rays as an element capable of inducing mutations. Using mutagenized corn lines, McClintock identified ring chromosomes, which are circular DNA structures generated by the fusion of the ends of a single irradiated chromosome. During this time, he also demonstrated the existence of the nucleolar organizer in a region of corn chromosome 6, which was found to be essential for nucleolus assembly.
Barbara McClintock received a grant from the Guggenheim Foundation which paid her six months of apprenticeship in Germany in 1933 and 1934. Her initial plan was to work with geneticist Curt Stern, a researcher who demonstrated the crossbreeding in Drosophila (flies ) weeks after she and Creighton did the same with the corn, but it turns out that Stern emigrated to the United States at that time. For this reason, the laboratory that McClintock ultimately accepted was that of Richard B. Goldschmidt.
Due to the political tension in Germany at the time, when he saw the impending rise of the Nazis, McClintock returned to Cornell., where she remained until 1936. This year, she obtained the post of assistant professor in the department of botany at the University of Missouri-Columbia.
Experiences in Missouri
While at the University of Missouri, McClintock continued the lineage of X-ray mutagenesis. He observed that chromosomes break down and fuse under these conditions, but so do endosperm cells spontaneously. He found out how the ends of the broken chromatids come together after DNA replication in the mitosis phase.
More precisely, it was during anaphase that the broken chromosomes formed a color bridge, which disappeared when the chromatids moved towards the cell poles. These breaks disappeared, forming bonds during the interphase of the next mitosis, repeating the cycle and causing massive mutations, leading to the appearance of a variegated endosperm.
This cycle of chromosomal breakage, fusion and bridging was considered a pivotal discovery at the time.. First, because it showed that chromosome binding was not a random process, and second, because it identified a mechanism for producing mutations on a large scale. In fact, this finding is so important that it is still used today, especially in the study of cancer research.
Although his research has yielded very green shoots in Missouri, McClintock was not at all happy with his place. She felt excluded from faculty meetings and was not informed of vacancies by other institutions. Although she initially had a lot of support from her peers, her academic competitiveness and the fact that she was an independent and lonely woman made her increasingly distant from her research.
An unpleasant anecdote which will prove to be underestimated by some of his colleagues is that in 1936 an advertisement for a woman of the same name and surname appeared in the newspapers. Confusing this woman with her, her manager threatened to fire her if she married. At the time, McClintock was already vice-president of the Genetic Society of the United States.
McClintock had lost faith in his coordinator Stadler and in the administration of the University of Missouri. Therefore, when he received an invitation in 1941 from the director of the genetics department of the Cold Spring Harbor laboratory to spend the summer there, he immediately accepted it. He did so to look for a job somewhere else in Missouri, trying his luck.
Also at this time, he would accept the post of Visiting Professor at Columbia University, where his colleague Marcus Rhoades was a professor. He offered to share his line of research with Cold Spring Harbor on Long Island. In December 1941, he was offered a research position at the Cold Spring Harbor Laboratory, part of the genetics department of the Carnegie Institution in Washington. I would eventually accept it.
Research at Cold Spring Harbor
After a year of part-time work at Cold Spring Harbor, Barbara McClintock accepted a full-time research position. There, he will continue his work on the rupture-fusion-bridge cycle, an extraordinarily productive period in scientific publications.
As a result of this prolific research, McClintock was recognized in 1944 as an academic at the United States National Academy of Sciences, being the third woman to be elected.. A year later, she was named president of the Genetics Society of America, an honor that had never been bestowed on a woman.
On the recommendation of geneticist George Beadle, in 1944 he performed a cytogenetic analysis on the fungus Neurospora crassa. Beadle had shown a gene-enzyme relationship when working with this fungus for the first time. McClintock determined the karyotype of the fungus as well as its life cycle, and since then N. crassa has been used as a model organism in genetic studies.
Discovery of gene regulation
Mcclintock spent the summer of 1944 understanding the biological mechanism behind the genetic mosaic phenomenon, a genetic disease that causes the seeds of the same ear of corn to have different colors. He found two places on the chromosomes (locus) which he named “Dissociator” (Ds) and “Activator” (Ac). Ds was linked to chromosomal breakage, in addition to affecting the activity of neighboring genes when Ac was present. In 1948, he discovered that the two loci were transposable elements that could change their place on the chromosome.
McClintock studied the transposition effects of Ac and Ds analyze the coloring patterns in corn kernels over generations of crosses. His observations led him to conclude that Ac controlled the Ds transposition of chromosome 9, and that its transposition was the cause of the chromosomal break.
When Ds moves, the gene that determines the color of the aleurone (corn seed) is expressed, because the suppressive effect of Ds is lost and, as a result, the appearance of color occurs. This transposition is random, which means that it will not affect all cells, which is why mosaicism occurs in infructescence. McClintock also determined that the transposition of Ds is determined by the number of copies of Ac.
During the 1950s developed a hypothesis that explained how transposable elements regulate the action of genes, by inhibiting or modulating them. He defined Ds and Ac as control units or regulatory elements, to clearly separate them from genes. He hypothesized that gene regulation may explain how multicellular organisms can diversify the characteristics of each cell, even though their genome is the same. This idea completely changed the concept of the genome, which until then had been interpreted as a simple set of static instructions.
McClintock’s work on the regulatory and control elements of genes was so complex and novel that the rest of the scientific community has shown some distrust of their findings. In fact, she herself described this response as a mixture of bewilderment and hostility. Still, McClintock went ahead and continued his line of research.
He then identified a new regulatory element called “Suppressor-Mutator” (Spm) which, although similar to Ac and Ds, performed more complex functions. However, given the reactions of the scientific community at the time and McClintock’s perception that he was moving away from the mainstream, he stopped publishing his findings.
Recognitions and past years
In 1967, McClintock retired from his post at the Carnegie Institution, being named a distinguished member thereof. This distinction allowed him to continue working as a Distinguished Scientist at the Cold Spring Harbor Laboratory with his fellow graduate students. In fact, she remained affiliated with the lab until the day of her death.
In 1973, he confessed why he had decided not to continue publishing his findings on the regulatory elements, although he continued to investigate on his own. He commented that due to his experience in the labs, it is very difficult to make another person aware of his unspoken assumptions. He believed that due to the fixed ideas of many scientists, some advancements could not be shared at any given time, as criticism would be assured. You have to wait for a conceptual change and communicate it at the right time.
His experience reinforced his opinions in this regard, because it took decades for their conclusions to be taken into account. Barbara McClintock’s work was not fully appreciated until, in the 1960s, geneticists François Jacob and Jacques Monod reached similar conclusions with their respective studies, outlined in a 1961 article titled “Mechanisms of Genetic Regulation in protein synthesis “(” Genetic mechanisms regulating protein synthesis “). McClintock read the book and compared his conclusions with those raised by the French.
Fortunately, McClintock eventually gained wide recognition for his work. His discovery of transposition was valued when this same process was described by other authors in bacteria and yeasts in the 1960s and 1970s. Ac and Ds were cloned in the 1970s and were considered to be transposons class II.
Ac is a complete transposon, which encodes a functional transposase in the sequence, allowing the element to move through the genome. Instead, Ds encodes a mutated, non-functional version of transposase and requires the presence of Ab in order to jump into the genome, which fits McClintock’s functional description. Subsequent studies have shown that these sequences do not move if they are not under stress, such as radiation breakdown or the like, so their activation could be an evolutionary source of variability.
Mcclintock he understood the role of these agents as evolutionary agents even before other scientists suspected him. Indeed, today the Ac / Ds system is used as a mutagenesis tool in plants, to characterize genes of unknown function and in species other than those of maize.
Thanks to the fact that the truth of her findings and the value of her work, applicable beyond the realm of botany, were finally recognized, Barbara McClintock was awarded the Nobel Prize in Physiology in 1983, becoming the seventh woman to to do. other occasions, received by one person. The Nobel Prize in Science is usually won by research teams, but since McClintock had to work alone for most of his life, the only merit was.
Barbara McClintock died of natural causes on September 2, 1992 at Huntington Hospital near the Cold Spring Harbor Laboratory where she lived so many times. Was he ninety years old and died without leaving children or ever having been married?
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