As early as 1868, people have discovered nucleic acids. In the laboratory of German chemist Hope Seiler, there is a Swiss graduate student named Michel (1844~ 1895). He was very interested in the bandage with purulent blood thrown by a hospital near the laboratory, because he knew that purulent blood was the "remains" of white blood cells and human cells that died in the "battle" with germs to protect human health. So he carefully collected the purulent blood on the bandage and decomposed it with pepsin. As a result, he found that most of the cell debris was decomposed, but it had no effect on the nucleus. He further analyzed the substances in the nucleus and found that the nucleus contained a substance rich in phosphorus and nitrogen. Hope Sailor did an experiment with yeast, which proved that Michelle's discovery about substances in the nucleus was correct. So he named this substance separated from the nucleus "nuclide", and later found that it was acidic, so it was renamed "nucleic acid". Since then, people have carried out a series of fruitful research on nucleic acid.
At the beginning of the 20th century, German Koser (1853~ 1927) and his two students, Jones (1865~ 1935) and Levin (1869 ~1. Nucleotides are composed of bases, ribose and phosphoric acid. There are four bases (adenine, guanine, thymine and cytosine) and two riboses (ribose and deoxyribose), so nucleic acids are divided into ribonucleic acid (RNA) and deoxyribonucleic acid (DNA).
Levin, who was eager to publish the research results, mistakenly thought that the number of four bases in nucleic acid was equal, and inferred that the basic structure of nucleic acid was polymerized from four nucleotides with different bases into four nucleotides of nucleic acid, and put forward the "four-nucleotide hypothesis". This false assumption greatly hinders people's understanding of the complex nucleic acid structure, and also affects people's understanding of the function of nucleic acid to some extent. It is believed that although nucleic acid exists in an important structure-nucleus, its structure is too simple to imagine what role it can play in the genetic process.
Protein's discovery was 30 years earlier than that of nucleic acid, and it developed rapidly. In the 20th century, 12 of the 20 amino acids that make up protein have been discovered, and all of them have been discovered by 1940.
1902, the German chemist Fischer put forward the theory that amino acids are linked by peptide chains to form protein. In 19 17, he synthesized a 18 peptide chain consisting of 15 glycines and 3 leucines. Therefore, some scientists think that protein may play a major role in heredity. If a nucleic acid is related to heredity, it must be a nucleoprotein linked to protein. Therefore, the biological community at that time generally tended to think that protein was the carrier of genetic information.
1928, American scientist Griffith (1877~ 194 1) experimented on mice with an encapsulated highly toxic pneumococcus and an uncoated low toxic pneumococcus. He killed pod-bearing bacteria at high temperature and injected them into mice together with live bacteria without pods. As a result, he found that the mouse soon became ill and died, and at the same time, he isolated live pod bacteria from the blood of the mouse. This shows that Agabi actually got something from the dead Agabi, thus transforming Agabi into Agabi. Is this assumption correct? Griffith did the experiment in the test tube again, and found that when the dead pod fungi and the live pod fungi were cultured in the test tube at the same time, all the pod fungi became pod fungi, and found that it was the residual nucleic acid in the shell of the dead pod fungi that made the pod fungi grow protein pods (because the nucleic acid in the pod was not destroyed during heating). Griffith called this nucleic acid a "transforming factor".
1944, American bacteriologist Avery (1877~ 1955) isolated an active "transforming factor" from a pod fungus, and made an experiment to check whether there was protein in this substance. The result was negative, which proved that the "transforming factor" was DNA. However, this discovery has not been widely recognized. People suspect that the technology at that time could not remove protein, and the residual protein played a role in transformation.
The phage group of German-American scientist Delbrouck (1906~ 198 1) firmly believes Avery's discovery. Because they observed the morphology of phage and the growth process of entering Escherichia coli under electron microscope. Phage is a virus that takes bacterial cells as its host. It is so small that it can only be seen with an electron microscope. Like a tadpole, it has a head membrane and a tail sheath composed of protein. The head contains DNA, and the tail sheath has tail silk, matrix and small hook. When phage infects Escherichia coli, its tail is first tied to the bacterial cell membrane, and then all the DNA in it is injected into the bacterial cells. Protein's empty shell is left outside the bacterial cells, which has no effect. After phage DNA enters bacterial cells, phage DNA and protein are rapidly synthesized by using substances in bacteria, thus many new phages with the same size and shape as the original ones are replicated. These phages will leave the dead bacteria and infect other bacteria before the bacteria are completely decomposed.
In 1952, hershey, the main member of the phage group, and his student Chase used the advanced isotope labeling technology to do the experiment of phage infecting Escherichia coli. He labeled the nucleic acid of E.coli T2 phage with 32P and the protein shell with 35S. Escherichia coli was infected with T2 phage, and then it was isolated. As a result, the phage left an empty shell with 35S label outside the Escherichia coli, only the nucleic acid with 32P label inside the phage was injected into the Escherichia coli, and the phage successfully propagated in the Escherichia coli. This experiment proves that DNA has the function of transmitting genetic information, and protein is synthesized by the instructions of DNA. This result was immediately accepted by the academic community.
Almost at the same time, Austrian biochemist Chagav made achievements in redetermining the contents of four bases in nucleic acid. Under the influence of Avery's work, he thinks that if different biological species are produced by different DNA, then the structure of DNA must be very complicated, otherwise it will be difficult to adapt to the diversity of the biological world. Therefore, he doubted Levin's "Tetranucleotide Hypothesis". In the four years from 1948 to 1952, he used paper chromatography which was more accurate than that in Levin's time to separate four kinds of bases, and used ultraviolet absorption spectrum for quantitative analysis. After repeated experiments, he finally got a different result from Levin. The experimental results show that the total number of purines and pyrimidines in DNA macromolecules is equal, among which adenine A and thymine T are equal, and guanine G and cytosine C are equal. It shows that the bases A and T, G and C in DNA molecules are paired, thus denying the "four nucleotide hypothesis" and providing important clues and basis for exploring the molecular structure of DNA.
1953 On April 25th, the British magazine Nature published the research results of Watson and Crick in Cambridge University: the molecular model of DNA double helix structure, which was later hailed as the greatest discovery in the field of biology since the 20th century, marking the birth of molecular biology.
Watson was an extremely clever boy in middle school. He entered the University of Chicago at the age of 15. At that time, Watson had the opportunity to study various biological science courses because of an experimental education plan that allowed early admission. During his college years, Watson had little formal training in genetics, but since reading Schrodinger's What is Life? -the physical appearance of living cells ",prompted him to" discover the secret of genes ". He is good at brainstorming, learning from others and enriching himself with other people's ideas. As long as there are convenient conditions, you can get the knowledge you need without forcing yourself to learn the whole new field. Watson received his doctorate at the age of 22 and was sent to Europe for postdoctoral research. In order to fully understand the chemical structure of virus genes, he went to the laboratory in Copenhagen, Denmark to study chemistry. Once he and his tutor went to Naples, Italy to attend a biomacromolecule conference, and had the opportunity to listen to British physical biologist Wilkins (19 16~? ) and saw Wilkins' DNA X-ray diffraction photos. Since then, the idea of finding the key to unlock the DNA structure has been lingering in Watson's mind. Where can I learn to analyze X-ray diffraction patterns? So he went to the Cavendish laboratory of Cambridge University in England to study, during which Watson met Crick.
Crick was enthusiastic about science when he was in middle school, and 1937 graduated from London University. In 1946, what does he read about life? -The physical appearance of living cells, determined to apply the knowledge of physics to the study of biology, and became interested in biology since then. 1947, repeat graduate student. 1949, he and Peruz used X-ray technology to study the molecular structure of protein, so he met Watson here. At that time, Crick was older than Watson 12 years old, and had not yet obtained his doctorate. But their conversation was so speculative that Watson felt lucky to find someone here who knew that DNA was more important than protein. At the same time, Watson thinks Crick is the smartest person he has ever met. They talk for at least a few hours every day to discuss academic issues. Two people complement each other, criticize each other and encourage each other. They believe that solving the molecular structure of DNA is the key to solving the genetic mystery. Only with accurate X-ray diffraction data can we find out the structure of DNA more quickly. In order to get the data of DNA X-ray diffraction, Crick invited Wilkins to Cambridge for the weekend. In the conversation, Wilkins accepted the view that DNA structure is spiral, and also talked about his collaborator Franklin (1920~ 1958, female) and the scientists in the laboratory, who are also trying to think about the problem of DNA structure model. During the period from 195 1 year,1month to1April, 953, Watson and Crick had several important academic exchanges with Wilkins and Franklin.
195 1 year1month, Watson was deeply inspired after listening to Franklin's detailed report on DNA structure. Watson and Crick, who have some knowledge of crystal structure analysis, realize that if they want to build a DNA structure model quickly, they can only use other people's analysis data. They quickly put forward the idea of triple helix DNA structure. At the end of 195 1, when they invited Wilkins and Franklin to discuss this model, Franklin pointed out that they underestimated the water content of DNA by half, so the first model was declared a failure.
One day, Watson went to Wilkins Laboratory at King's College, and Wilkins took out Franklin's recent X-ray diffraction photos of "type B" DNA. Watson got excited immediately after seeing the photo, and his heart beat faster, because this image is much simpler than the previous "A type". Just look at the "B-type" X-ray diffraction photos, and then after simple calculation, we can determine the number of polynucleotide chains in DNA molecules.
Crick asked a mathematician to help him calculate, and the results showed that purine had a tendency to attract pyrimidine. According to this result and the result that two purines and two pyrimidines of nucleic acid obtained from Chagaff are equal, they formed the concept of base pairing.
They think hard about the sequence of four bases, draw the base structure on paper again and again, fiddle with the model, put forward assumptions again and again, and overthrow their own assumptions again and again.
Once, Watson was repairing the model according to his own ideas. He moved bases to look for various pairing possibilities. Suddenly, he found that the adenine-thymine pair connected by two hydrogen bonds had the same shape as the guanine-cytosine pair connected by three hydrogen bonds, so his spirit was greatly uplifted. Because the mystery of why purine and pyrimidine have exactly the same number is about to be solved. Chagaff's law suddenly became the inevitable result of DNA double helix structure. Therefore, it is not difficult to imagine how to use one strand as a template to synthesize another strand with complementary base sequence. Then, the skeletons of the two chains must be in opposite directions.
After intense and continuous work by Watson and Crick, the DNA metal model was quickly assembled. From this model, we can see that DNA consists of two nucleotide chains, which are intertwined in opposite directions along the central axis, much like a spiral staircase. The armrests on both sides are the skeleton of two sugar-phosphorus groups with alternating polynucleotide chains, and the pedals are base pairs. Due to the lack of accurate X-ray data, they dare not conclude that the model is completely correct.
The next scientific method is to carefully compare the diffraction pattern predicted by this model with the experimental data of X-ray. They called Wilkins again. In less than two days, Wilkins and Franklin confirmed the correctness of the double helix structure model with X-ray data analysis, and wrote two experimental reports, which were published in the British journal Nature. 1962, Watson, Crick and Wilkins won the Nobel Prize in Medicine and Physiology, while Franklin died of cancer in 1958 and didn't win the prize.
After the discovery of DNA double helix structure, it greatly shocked the academic circles and inspired people's thoughts. Since then, people have immediately carried out a lot of molecular biology research centered on genetics. Firstly, an experimental study was carried out on how to arrange and combine four bases to encode and express 20 amino acids. 1967, the gene code was completely cracked, and the gene gained a new concept at the level of DNA molecule. It shows that gene is actually a fragment of DNA macromolecule, and it is the functional unit and structural unit of genetic material that controls biological traits. Many nucleotides on this unit fragment are not randomly arranged, but arranged in a meaningful cryptographic order. A certain structure of DNA can control the synthesis of protein of the corresponding structure. Protein is an important part of organisms, and the characteristics of organisms are mainly reflected by protein. Therefore, the control of genes on traits is realized by DNA controlling the synthesis of protein. On this basis, genetic engineering, enzyme engineering, fermentation engineering, protein engineering and so on have emerged one after another. The development of these biotechnology will surely make people use biological laws to benefit mankind. With the development of modern biology, the trend that it will become a leading discipline is more and more obvious.