The theoretical leap and development of modern biology(2)
2 DNA double helix: the cornerstone of modern biology
2.1 The discovery process of DNA double helix structure
2.1.1 early explorations: the search for genetic material
In the long history of the development of biology, the exploration of genetic material has been one of the core issues concerned by scientists. As early as the 19th century, Gregor Mendel discovered the basic laws of inheritance, namely the law of separation and the law of free combination, through pea hybridization experiments. His research showed that the genetic traits of organisms are determined by genetic factors (later called genes), which are passed on in a specific way between parents and offspring. Mendel's work laid a solid foundation for the development of genetics, enabling people to begin to understand genetic phenomena from a scientific perspective. However, at that time Mendel did not know what the material basis of genetic factors was, and this question became the direction of subsequent scientists to explore.
In the early 20th century, Thomas Hunt Morgan conducted a series of genetic studies using fruit flies as experimental materials. Through genetic analysis of traits such as eye color and wing shape in fruit flies, he discovered the law of gene linkage and interchange, further confirming that genes are located on chromosomes. Morgan's research not only enriched Mendel's theory of inheritance, but also provided important clues for the study of genetic material. His experiments showed that chromosomes play a key role in the process of inheritance, and chromosomes are mainly composed of proteins and DNA, which led scientists to wonder whether proteins or DNA carry genetic information.
During this period, the development of chemical analysis techniques made it possible to study the chemical composition of genetic material. Scientists gradually realized that DNA was a large molecule composed of four deoxynucleotides, while proteins were composed of twenty amino acids. Due to the more complex and diverse composition of proteins, many scientists at the time believed that proteins were more likely to be genetic material. For example, in the 1944 Pneumococcus transformation experiment conducted by Oswald Avery, although DNA was initially proved to be genetic material, it was not widely recognized at that time due to some limitations of the experiment. It was not until 1952 that Alfred Hershey and Martha Chase proved conclusively that DNA was genetic material by using bacteriophages to infect bacteria. They tagged the DNA and proteins of bacteriophages with radioisotopes, and then let the bacteriophages infect the bacteria. They found that only the DNA entered the bacteria and could guide the synthesis of new phages, providing strong evidence for DNA as genetic material.
2.1.2 key breakthrough: the birth of the double helix structure
After identifying DNA as genetic material, scientists began to work on revealing its structure. In the early 1950s, British scientists Maurice Wilkins and Rosalind Franklin used X-ray diffraction to study DNA. Franklin improved his experimental techniques to take very clear X-ray diffraction pictures of DNA, which showed that DNA had the characteristics of a helical structure. However, Franklin was cautious about his research results and did not immediately make a clear inference about the structure of DNA.
At the same time, the American scientist James Watson and the British scientist Francis Crick are also actively studying the structure of DNA. They cooperate at the Cavendish Laboratory at Cambridge University, using the method of building models to predict the structure of DNA. Although Watson and Crick are not experts in X-ray crystallography, they are good at synthesizing various information and combining knowledge and research results from different fields. They learned about the progress of Wilkins and Franklin's X-ray diffraction research, as well as the pattern of DNA base composition discovered by Erwin Chargaff (that is, the number of adenine A and thymine T is equal, and the number of guanine G and cytosine C is equal). On this basis, they continuously adjusted the parameters and structure of the model after many attempts and failures. In February 1953, Watson and Crick saw "Photo 51" taken by Franklin, and this clear X-ray diffraction photo of DNA provided them with key clues. They immediately realized that DNA is a double helix composed of two opposite and parallel strands, with bases located inside the helix and connected to each other by complementary pairing. Then they quickly constructed the DNA double helix structure model, which perfectly explains the mechanism of DNA's genetic information storage and transmission.
On April 25, 1953, Watson and Crick published a paper in the journal Nature entitled "Molecular Structure of Nucleic Acid - A Structural Model of Deoxyribonucleic Acid", formally proposing the DNA double helix structure model. The proposal of this model was like a blockbuster and caused a huge sensation in the scientific community. It not only revealed the molecular structure of DNA, but also provided a reasonable explanation for the transmission and replication of genetic information, enabling people to understand genetic phenomena from the macroscopic level to the molecular level. The birth of the DNA double helix structure model marked the beginning of modern molecular biology and laid a solid foundation for the subsequent development of genetic research, genetic engineering and other fields.
2.1.3 follow-up verification: confirmation and improvement of the structure
The DNA double helix model proposed by Watson and Crick was of great theoretical significance, but it was not immediately widely accepted at the time, and further experimental verification and refinement were required. Many scientists have questioned this model, arguing that it may be too simple to explain some of the complex properties of DNA.
Although Franklin played an important role in the discovery of the DNA double helix structure, she also initially had reservations about Watson and Crick's model. She continued her research and further verified some of the characteristics of the DNA double helix structure through more in-depth X-ray diffraction analysis. Her results showed that the base pairing mode in the DNA double helix structure was reasonable and consistent with the X-ray diffraction data. Franklin's work provided important experimental support for the DNA double helix structure model, and her research results were gradually recognized by the scientific community.
Chagaf's law also played a key role in the verification of DNA double helix structure. Chagaf discovered the law of A = T and G = C by analyzing the base composition of various biological DNA. This law is in line with the principle of base complementary pairing proposed by Watson and Crick, which further proves the correctness of the DNA double helix structure model. If DNA does not form the double helix structure according to this complementary pairing of bases, the relationship between the number of bases in Chagaf's law cannot be explained.
In addition to X-ray diffraction analysis and base composition analysis, other scientists have also verified the DNA double helix structure from different angles. For example, some scientists have studied the physical and chemical properties of DNA, such as density, viscosity, etc., and found that these properties are consistent with the predictions of the double helix structure model. Others have found that the DNA double helix structure can well explain the transmission and replication mechanism of genetic information through the study of the DNA replication process. During DNA replication, the two strands are untied, and each serves as a template to synthesize new complementary strands, thus ensuring the accurate transmission of genetic information.
With the passage of time, more and more experimental evidence supports the DNA double helix model, which is gradually accepted by the scientific community. At the same time, scientists are constantly refining and developing it. They found that DNA double helix structure exists in a variety of conformations, in addition to the classic B-type DNA, there are A-type DNA and Z-type DNA, etc. These different conformations play an important role in different biological processes. Research on the interaction between DNA and proteins has also continued to deepen, revealing how DNA works with various proteins in the cell to regulate the expression of genes and the transmission of genetic information. Through subsequent verification and improvement, the DNA double helix structure model has gradually become the cornerstone of modern biology, providing an important theoretical framework for the development of life science.
2.2 Characteristics and functions of DNA double helix structure
2.2.1 structure characteristics: the composition and arrangement of double helix
The DNA double helix structure is like an exquisite collection of life codes, and its composition and arrangement contain the mystery of life inheritance. From a microscopic perspective, DNA molecules are composed of deoxyribose, phosphoric acid and bases. As a five-carbon sugar, deoxyribose is alternately connected with phosphate groups to form the skeleton structure of DNA molecules, which is like a sturdy rope that provides a stable support for the entire DNA molecule. Phosphate groups are connected to deoxyribose through phosphate diester bonds. This connection method not only endows DNA molecules with stability, but also provides the necessary chemical basis for the transmission and replication of genetic information.
In the DNA double helix structure, bases play a crucial role as carriers of genetic information. The bases mainly include adenine (A), thymine (T), guanine (G) and cytosine (C). These four bases are arranged on the inside in a specific way to form the core coding region of the DNA molecule. Two reverse parallel polynucleotide chains are connected to each other through hydrogen bonds between bases, thus forming a unique double helix structure. The two strands of this double helix structure are not entangled at will, but follow a strict principle of complementary pairing of bases. Specifically, adenine (A) is always paired with thymine (T), and they are connected by two hydrogen bonds; guanine (G) is always paired with cytosine (C), and they are connected by three hydrogen bonds. This precise base complementary pairing allows DNA molecules to accurately convey genetic information during replication and transcription.
From the perspective of spatial structure, the DNA double helix structure shows the shape of a right-handed helix. Each rotation contains 10 base pairs and the pitch is about 3.4 nanometers. This helical structure allows DNA molecules to hold a large amount of genetic information in a limited space. At the same time, there are also large and small grooves in the double helix structure. The existence of large and small grooves provides specific check points for the interaction of DNA with other biological macromolecules such as proteins. Many transcription factors and regulatory proteins can bind to DNA molecules by recognizing specific base sequences in large and small grooves, thereby regulating the expression of genes. For example, in the process of gene transcription, transcription factors can bind to specific regions in the big groove, promote the binding of RNA polymerase to DNA, and initiate gene transcription. This molecular recognition mechanism based on the double helix structure plays a key regulatory role in the growth and development of organisms, cell differentiation and other life processes.
2.2.2 Genetic Information Transfer: DNA Duplication and Transcription
One of the important functions of the DNA double helix structure is to achieve accurate transmission of genetic information. This process is mainly completed through the replication and transcription of DNA. DNA replication is the foundation of genetic information transmission, which ensures that daughter cells can obtain the same genetic material as parent cells. Before cell division, DNA needs to be replicated precisely in order to provide complete genetic information to the newly formed cell. The process of DNA replication is like a delicate molecular machine operation, involving the synergistic action of multiple enzymes and proteins.
DNA helicase first binds to the DNA double helix structure, and by consuming energy, the two double strands are untied to form two single-stranded templates. This process is like unzipping, exposing the internal structure of the DNA molecule. Subsequently, DNA polymerase uses the unzipped single strand as a template and adds free deoxynucleotides to the newly synthesized DNA strand one by one according to the principle of base complementary pairing. Since DNA polymerase can only synthesize DNA strands along the 5 'to 3' direction, the replication method on the two template strands is different. On one template strand, DNA polymerase can continuously synthesize new DNA strands, which are called precursor strands; on the other template strand, DNA polymerase needs to segment and synthesize short DNA fragments, which are called Okazaki fragments. These Okazaki fragments are then joined by DNA ligases to form a complete DNA strand, which is called a subsequent strand. During the entire replication process, DNA polymerase has a proofreading function, which can identify and correct errors during replication, thus ensuring the accuracy of genetic information transmission. According to studies, the error rate during DNA replication is extremely low, with approximately one error per 10 ^ 9 to 10 ^ 10 base pairs replicated. This high degree of accuracy is essential for maintaining the genetic stability of an organism.
Transcription is the process of transferring genetic information from DNA to RNA, and it is the first step in gene expression. During the transcription process, a strand of DNA is used as a template, and under the action of RNA polymerase, an RNA strand is synthesized that is complementary to the template strand. RNA polymerase first recognizes and binds to a specific region on the DNA molecule, which is called a promoter. The promoter contains specific base sequences that can interact with RNA polymerase and its cofactors to initiate the transcription process. Unlike DNA replication, the transcription process requires only one DNA strand as a template, and in the synthesized RNA strand, uracil (U) replaces thymine (T) and pairs with adenine (A). The RNA polymerase moves along the DNA template strand, adding ribonucleotides to the RNA strand being synthesized one by one according to the principle of base complementary pairing. When the RNA polymerase encounters the termination sequence, the transcription process ends and the synthesized RNA strand is released from the DNA template. The RNA produced by transcription can be divided into messenger RNA (mRNA), transfer RNA (tRNA) and ribosomal RNA (rRNA) according to their different functions. Among them, mRNA carries the genetic information in DNA as a template for protein synthesis; tRNA is responsible for transporting amino acids during protein synthesis; rRNA is a component of ribosome and participates in protein synthesis.
2.2.3 impact on biodiversity
DNA double helix structure plays a central role in determining the genetic diversity of organisms, and it is an important basis for biological evolution and adaptation to the environment. Genetic diversity refers to the sum of various genetic information carried by all organisms on earth, and it is an important part of biodiversity. The sequence of bases in the DNA double helix structure determines the diversity of genes, and the diversity of genes directly affects the traits and functions of individual organisms. There are differences in DNA sequences between different species and between different individuals of the same species, and these differences lead to the diversity of organisms in morphology, physiology, and behavior. For example, the DNA sequences of humans and chimpanzees are more than 98% similar, but it is the difference of less than 2% that determines the vast differences in intelligence, language, and social behavior between humans and chimpanzees.
Gene mutation is one of the important causes of genetic diversity, which refers to the replacement, addition or deletion of base pairs in DNA molecules. Gene mutations can occur spontaneously or can be induced by physical, chemical and biological factors. When genetic mutations occur in the coding region of genes, they may cause changes in the amino acid sequence of proteins, which affect the structure and function of proteins, and then change the traits of organisms. Sickle cell anemia is a genetic disease caused by genetic mutations. Under normal circumstances, in the DNA sequence of human hemoglobin genes, the base pair at a certain position is A-T, the corresponding codon on the transcribed mRNA is GAG, and the translated amino acid is glutamic acid. In patients with sickle cell anemia, the base pair at this position is replaced, from A-T to T-A, the corresponding codon on the transcribed mRNA is changed to GUG, and the translated amino acid is valine. This amino acid change causes the structure of hemoglobin to be abnormal, causing red blood cells to become sickle-shaped and easily ruptured, which can lead to a series of symptoms such as anemia.
In addition to gene mutations, gene recombination is also an important mechanism for increasing genetic diversity. Gene recombination refers to the recombination of genes that control different traits during the process of sexual reproduction in an organism. During meiosis, cross-swaps occur between homologous chromosomes, which allows for the recombination of non-allelic genes located on homologous chromosomes. For example, during meiosis in Drosophila, eye color genes and wing shape genes on homologous chromosomes may be recombined through cross-swaps, resulting in new gene combinations that result in different eye colors and wing shapes in offspring Drosophila. In addition, during fertilization, gametes from the father and mother are randomly combined, resulting in different gene combinations, further increasing genetic diversity.
Genetic diversity is of great significance for the survival and evolution of organisms. It enables groups of organisms to better adapt to changes in the environment, increasing the chances of species surviving and reproducing under different environmental conditions. When the environment changes, there may be some individuals in groups of organisms with genetic diversity who carry genes for adapting to the new environment. These individuals are able to survive in the new environment and pass these favorable genes on to future generations, thus promoting the evolution of the species. During the use of antibiotics, there may be some individuals with resistance genes in the bacterial population. When antibiotics are present in the environment, these bacteria with resistance genes are able to survive and multiply in large numbers, while other bacteria without resistance genes are eliminated. Over time, the frequency of resistance genes in bacterial populations increases, leading to increased antibiotic resistance. This genetic diversity-driven evolutionary process allows organisms to continuously adapt to changes in their environment, allowing species to survive and multiply.
2.3 The influence of DNA double helix structure on modern biology
Rise and Development of 2.3.1 Molecular Biology
The discovery of the DNA double helix structure was undoubtedly a key turning point in the rise of molecular biology, injecting a strong impetus into the vigorous development of this discipline. Before 1953, although biological research had achieved certain results in many fields, the understanding of life phenomena mostly stayed at the macroscopic and cellular levels, and the transmission and expression mechanisms of genetic information were poorly understood. The proposal of the DNA double helix structure model was like a dawn, illuminating a new direction in biological research, enabling scientists to delve into the mysteries of life from the molecular level.
This discovery has prompted many scientists to devote themselves to the field of molecular biology, attracting talents from different disciplinary backgrounds. Physicists, chemists, biologists, and others have used the methods and technologies of their respective disciplines to jointly explore the structure and function of DNA, as well as the transmission and regulation mechanism of genetic information at the molecular level. This interdisciplinary research model has become a significant feature of the development of molecular biology, which has greatly promoted the rapid development of this discipline. Crick not only played a key role in the discovery of the double helix structure of DNA, but also made important contributions to the study of the genetic code. He proposed the "central dogma", which holds that genetic information is passed from DNA to RNA, and then from RNA to protein. This law laid an important theoretical foundation for the development of molecular biology. Since then, scientists have conducted in-depth studies around the "central dogma", further revealing the complex mechanisms in the transmission of genetic information, such as transcription, translation, RNA splicing, etc.
With the deepening of research, new theories and technologies continue to emerge in the field of molecular biology. In the study of DNA replication mechanism, scientists have discovered a variety of enzymes and proteins involved in the replication process, such as DNA polymerase, helicase, etc., and detailed how DNA replicates in a semi-reserved manner to ensure the accurate transmission of genetic information. In terms of gene expression regulation, important elements and molecules such as promoters, enhancers, and transcription factors have been discovered, revealing the fine regulation mechanism of gene expression at the transcription level and translation level. These research results not only enrich the theoretical system of molecular biology, but also provide solid theoretical support for the development of application fields such as genetic engineering and biotechnology.
The development of molecular biology has also led to the innovation of related technologies. The continuous progress of nucleic acid sequencing technology has enabled scientists to quickly and accurately determine the sequence of DNA and RNA, providing an important means for the study of gene function. From the original Sanger sequencing method to today's high-throughput sequencing technology, the sequencing speed and throughput have been greatly improved, but the cost has been greatly reduced. This has made it possible to sequence large-scale genomes. The completion of the Human Genome Project is one of the important achievements of the development of nucleic acid sequencing technology. Through the sequencing of the human genome, we have a deeper understanding of the whole picture of human genetic information, providing an important basis for studying the genetic mechanism of human diseases and developing personalized treatment plans. The emergence of gene editing technologies such as CRISPR-Cas9 has revolutionized molecular biology research and biotechnology applications. This technology can precisely edit and modify DNA sequences, allowing scientists to conduct in-depth research on gene functions at the level of cells and organisms. It also brings new hope for gene therapy, crop genetic improvement and other fields.
2.3.2 in Genetic Engineering and Biotechnology
The discovery of DNA double helix structure provides a theoretical foundation for the development of genetic engineering and biotechnology, enabling scientists to precisely manipulate the genes of organisms and achieve a major leap from theory to practice. Genetic engineering refers to the rigorous design according to people's wishes, and through in vitro DNA recombination and transgenic technologies, new genetic characteristics are given to organisms, thereby creating new biological types and biological products that better meet people's needs. In genetic engineering, the understanding and application of DNA double helix structure is the key to realizing genetic manipulation.
In gene cloning, scientists use the ability of restriction enzymes to recognize and cut specific DNA sequences, cutting the target gene out of an organism's genome. Like precise molecular scissors, restriction enzymes can cut at specific locations in the DNA double helix to produce sticky or flat ends. The target gene is then joined to the vector DNA by DNA ligases to form recombinant DNA molecules. Vector DNA is usually bacterial plasmid or viral DNA that replicates autonomously in the host cell. After introducing the recombinant DNA molecule into the host cell, the host cell will regard it as part of itself for replication and expression, thus realizing the cloning of the target gene. Using gene cloning technology, scientists have successfully cloned many genes of important economic value and scientific significance, such as insulin genes, growth hormone genes, etc. The cloning of these genes provides important raw materials for the development of biopharmaceuticals and agricultural biotechnology.
Transgenic technology is one of the important applications of genetic engineering. It is to introduce foreign genes into the genome of the recipient organism to make it express and obtain new traits. In the field of agriculture, transgenic technology is widely used to breed crop varieties with excellent traits. The cultivation of transgenic insect-resistant cotton makes cotton acquire insect resistance by introducing the insect-resistant gene in Bacillus thuringiensis into the cotton genome. The protein encoded by this insect-resistant gene can specifically kill pests such as cotton bollworm, thereby reducing the use of pesticides and improving the yield and quality of cotton. Transgenic technology is also used to improve the disease resistance, stress resistance and nutritional value of crops. The rice blast resistance gene was transferred into transgenic rice, which improved the rice's resistance to rice blast; the vitamin A synthesis-related gene was added to transgenic corn, which improved the nutritional value of corn.
In the field of medicine, the development of gene diagnosis and gene therapy technology is also inseparable from the discovery of DNA double helix structure. Gene diagnosis is to diagnose gene mutations or abnormalities related to diseases by detecting the DNA sequence of organisms. Polymerase chain reaction (PCR) technology is one of the commonly used techniques in gene diagnosis. It uses the characteristics of DNA double helix structure to rapidly amplify specific DNA fragments in vitro. By sequencing or other analysis methods of the amplified DNA fragments, the type and location of gene mutations can be accurately detected. Gene diagnosis technology has played an important role in the diagnosis of hereditary diseases, early diagnosis of tumors and detection of pathogens. Gene therapy is the introduction of normal genes into diseased cells to correct or compensate for diseases caused by genetic defects and abnormalities. For some single-gene genetic diseases, such as cystic fibrosis and hemophilia, gene therapy has brought hope for a cure. Although gene therapy is still in the research and clinical trials stage, it has achieved some encouraging results.
The discovery of DNA double helix structure has also had a profound impact on biopharmaceuticals. Through genetic engineering technology, scientists can produce a large number of recombinant protein drugs, such as insulin, interferon, monoclonal antibodies, etc. These drugs have the advantages of high efficiency and strong specificity, providing new means for the treatment of many diseases. Insulin is an important drug for the treatment of diabetes. The traditional insulin production method is extracted from animal pancreas, with low yield and high cost. Using genetic engineering technology, the human insulin gene is introduced into Escherichia coli or yeast, and these engineered bacteria can be fermented to produce recombinant human insulin in large quantities, which meets the clinical needs. Monoclonal antibody technology is also based on DNA double helix structure and genetic engineering technology, which can produce high-purity antibodies against specific antigens and has important applications in the treatment of tumors and autoimmune diseases.
2.3.3 Transformation of Life Science Research Paradigm
The discovery of DNA double helix structure has profoundly changed the research paradigm of life science, promoting the transformation of research from macroscopic observation to microscopic molecular level, bringing new perspectives and methods to life science research. Before this discovery, life science research mainly relied on macroscopic observation and description of the morphology, structure and physiological function of organisms. Although these studies have accumulated a wealth of biological knowledge for us, the understanding of the essence and internal mechanisms of life phenomena is relatively limited.
With the revelation of the DNA double helix structure, scientists have begun to realize that the mystery of life phenomena is hidden at the molecular level, and the transmission and expression of genetic information is the key to understanding life processes. This realization has prompted life science research to gradually shift from macroscopic to microscopic, from the study of organisms as a whole to the study of cells, molecules and genes. In the field of cell biology, the research focus has shifted from the observation of the morphology and structure of cells to the exploration of molecular mechanisms within cells. Scientists have begun to pay attention to microscopic processes such as signal transduction pathways, protein-protein interactions, and regulation of gene expression within cells. Through the study of these microscopic processes, we have a deeper understanding of life activities such as cell growth, differentiation, and apoptosis. In tumor cells, studies have found that some gene mutations lead to abnormal activation of cell signal transduction pathways, which promote unlimited cell proliferation and metastasis. These research results provide new targets and ideas for tumor diagnosis and treatment.
In the field of genetics, the discovery of the DNA double helix structure has brought genetic research from classical genetics to the era of molecular genetics. Traditional classical genetics mainly infer the existence and function of genetic material by studying the inheritance laws of biological traits. Molecular genetics, on the other hand, studies the transmission, variation and expression regulation of genetic information directly from the molecular level of DNA. Through the analysis of DNA sequences, scientists can accurately locate genes, study the structure and function of genes, and the relationship between genes and traits. The implementation of the Human Genome Project has enabled us to have a clear understanding of the whole picture of the human genome and discovered many genes related to diseases. The discovery of these genes provides an important basis for the genetic diagnosis, prevention and treatment of diseases.
The development of molecular biology technology has also provided powerful tools and methods for life science research. In addition to the aforementioned nucleic acid sequencing technology and gene editing technology, there are also fluorescence in situ hybridization (FISH), Western blot technology, and immunoprecipitation technology. These technologies can help scientists study the structure, function, and interaction of biological macromolecules at the molecular level. FISH technology can be used to detect the location and expression of specific genes on chromosomes; Western blot technology can detect the expression level and modification status of proteins; and immunoco-precipitation technology can be used to study the interaction between proteins. The application of these technologies makes life science research more accurate and in-depth, and can reveal many previously difficult-to-discover life phenomena and laws.
This change in research paradigm has also promoted the cross-integration of life sciences with other disciplines. The integration of life sciences with physics, chemistry, computer science and other disciplines has become increasingly close, forming interdisciplinary disciplines such as biophysics, chemical biology, and bioinformatics. Biophysics uses the principles and methods of physics to study the structure and function of biomolecules, such as using X-ray crystallography and nuclear magnetic resonance technology to analyze the three-dimensional structure of proteins and nucleic acids; chemical biology uses chemical synthesis and analysis methods to study biomolecular interactions and biological processes, such as the development of new biological probes and drug molecules; bioinformatics uses computer science and mathematical methods to analyze and process biological data, such as genomic data analytics, protein structure prediction, etc. The development of these interdisciplinary fields has brought new ideas and methods to life science research, promoting the rapid development of life science.