Genetics: Unravelling the Structure of DNA

The story of DNA is a fascinating tale of discovery, intricate structure, and profound implications for life as humans know it. DNA, short for deoxyribonucleic acid, is a complex molecule that contains the instructions an organism needs to develop, survive, and reproduce. In virtually all living organisms, DNA is the hereditary material passed from parents to offspring, defining the blueprint for life.

This article will delve into the enigmatic world of DNA, exploring its double helix structure, and the crucial role of nucleotides and base pairs in its replication. It will also underscore the importance of DNA as the carrier of genetic information and how the study of this molecule has revolutionised various fields of research. From the early contributions of scientists like Rosalind Franklin to the latest advancements in genetic sequencing, it will journey through the rich history and significant breakthroughs in DNA research. Regardless of the background on the subject, this comprehensive look into the structure of DNA will offer valuable insights into the very essence of life.

Figure 1: Illustration of DNA as life by Sam Falconer. This piece was created to celebrate 70 years of DNA research progress since its discovery in 1953.

The Double Helix Structure of DNA

In 1953, James Watson and Francis Crick put forward the double helix model of DNA (Watson & Crick, 1953). This structure of DNA, which resembles a twisted ladder or a spiral staircase, has two strands that twist around each other. The uprights of the ladder are long chains of alternating sugar and phosphate molecules. The rungs of the ladder are composed of pairs of four kinds of nitrogen bases. This structure is perfect for storing information in a compact way, as it allows long DNA molecules to fit within a cell's limited space. Each of these nitrogen bases has a unique structure and function. Adenine (A) pairs with thymine (T), and cytosine (C) pairs with guanine (G). These bases act like the letters of an alphabet, forming a code that our cells can read (Calladine et al., 2004).

While the role of Watson and Crick in the discovery of this structure is crucial, it is essential to recognise the contribution of Rosalind Franklin. Franklin used X-ray diffraction techniques, a method that involves shining X-rays onto a target and studying the pattern they make when they bounce off. Her X-ray images of DNA, including the famous Photo 51, were integral in discovering the double helix structure (Franklin & Gosling, 1953). Unfortunately, Franklin's contribution was initially overlooked, but she is now widely recognised for her fundamental role in understanding DNA's structure.

Figure 2: The dicoverers of DNA: Franklin, Crick and Watson (Unknown, n.d.).

Nucleotides and Base Pairs: The Fundamental Units of DNA

Nucleotides are the basic building blocks of DNA. Think of a nucleotide as a building block in a Lego set, where each block is needed to create the whole structure, which in this case, is the DNA molecule. Each nucleotide is made up of three components: a sugar molecule called deoxyribose, a phosphate group, and a nitrogenous base (What Is DNA?: MedlinePlus Genetics, n.d.). In terms of the Lego analogy, consider deoxyribose as the base platform on which we start building. It’s a type of sugar, but not the kind you put in your tea or coffee. This is a more complex sugar and is crucial because it acts as a connecting point for the other two components. The phosphate group can be likened to the connectors that hold different Lego blocks together. In real-world terms, the phosphate group is a cluster of one phosphorus atom and four oxygen atoms. It plays a vital role in connecting the sugar part of one nucleotide to the sugar of the next nucleotide, thereby forming a chain. (Alberts et al., 2007) The nitrogenous base is the unique part of each block, like the different colours and designs on the top of each Lego piece. There are four types of these nitrogenous bases in DNA: Adenine (A), Thymine (T), Guanine (G), and Cytosine (C). These bases carry the actual genetic information. The four nitrogenous bases have a unique structure known as a ring structure. Based on their ring structure, they are divided into two categories: purines (adenine and guanine), which have a two-ring structure, and pyrimidines (cytosine and thymine), which have a single-ring structure (Alberts et al., 2007; Roy & Kundu, 2021).

The bases on one strand of DNA pair up with bases on the other strand, forming a rung of the DNA ladder. The structure of the bases and their chemical properties allow adenine to form a pair with thymine, and guanine to form a pair with cytosine. This is known as base pairing and is a key aspect of the structure and function of DNA. The pairing between these bases is not random; adenine always pairs with thymine, and guanine always pairs with cytosine. This specificity is due to the size and shape of the bases, as well as the number and arrangement of hydrogen bonds they can form. Hydrogen bonds are a type of attraction or "bond" that happens between molecules. They are named so because they always involve a hydrogen atom. Adenine and thymine can form two hydrogen bonds, while guanine and cytosine can form three, making G-C pairs slightly more stable than A-T pairs (Alberts et al., 2007; Calladine et al., 2004).

Figure 3: Chemical structure of the ladder like DNA (Unknown, n.d.).

DNA Replication and the Role of Nucleotides and Base Pairs

One of the most important features of DNA is its ability to replicate or make copies of itself. This is crucial because when cells divide, each new cell needs its copy of DNA to function and contribute to the organism's life processes (Alberts et al., 2007).

DNA replication starts with separating the two strands of the DNA molecule. This is done by enzymes, which are proteins that speed up chemical reactions. These enzymes break the bonds between the base pairs, causing the DNA molecule to "unzip" down the middle. Once the two strands are separated, each serves as a template for a new strand. The bases on the old strand pair up with free nucleotides in the cell according to the base-pairing rules, creating a new strand that complements the old one. Because each new DNA molecule contains one old strand and one new strand, this process is called semi-conservative replication. This method of replication ensures that the genetic information is accurately copied with each replication (Alberts et al., 2007; Wilhelm et al., 2020).

Figure 4: The steps of DNA replication (Uknown, n.d.).

DNA as the Carrier of Genetic Information

The arrangement of bases in a DNA molecule forms the instructions for the organism's development and function. This sequence of bases, read in groups of three, codes for specific amino acids, the building blocks of proteins. This language of three-letter "words" is called the genetic code. A gene is a section of a DNA molecule that contains the instructions for making a particular protein (Cooper, 2000).

The proteins produced as a result of these instructions’ influence the organism's traits, such as eye colour, blood type, and susceptibility to certain diseases. When cells divide, they pass on their DNA, and hence their instructions, to their offspring cells. This is how traits are inherited from parents to offspring. When the sequence of bases in a DNA molecule change, this can cause a mutation, leading to variations in traits, which can be harmful, beneficial, or neutral (Alberts et al., 2007). DNA's role as the carrier of genetic information is crucial to life as we know it. It provides the instructions for the development and functioning of organisms, and it is the basis for heredity and evolution.

Figure 5: Reading the DNA: the genetic code table (Pasieka, n.d.).

The Evolution of DNA Study and Its Impact on Research

Our understanding of DNA has evolved dramatically since the initial discovery of its structure. This understanding has led to significant advancements in several fields, including medicine, forensics, anthropology, and more. One of the major breakthroughs in science made possible through our understanding of DNA is genetic engineering. This technology allows scientists to modify the DNA of organisms, leading to the development of genetically modified crops that are resistant to pests and diseases, and the production of therapeutic proteins and hormones such as insulin (Berg & Mertz, 2010).

Additionally, the development of techniques to amplify and sequence DNA, such as the polymerase chain reaction (PCR) and next-generation sequencing, has revolutionised molecular biology. These techniques have enabled researchers to study genes and genetic variation in great detail (Mullis, 1990), leading to advancements in diagnosing and treating genetic diseases, identifying individuals in forensic investigations, and understanding the evolutionary relationships among species.

Moreover, our understanding of DNA has opened the door to personalized medicine. This is a new approach to healthcare that uses information about a person's genetic makeup to tailor their medical treatment (Manolio et al., 2013). This approach has the potential to increase the effectiveness of treatments and reduce their side effects, improving patient outcomes.

Figure 6: Sampling and analysing DNA (Unknown, n.d.).

Genetic Sequencing and Its Implications

With the advent of new technologies, our ability to read and interpret the genetic code has improved immensely. The sequencing of the human genome, completed in 2003 as a part of the Human Genome Project, is an example of such advancements. This project revealed that the human genome consists of approximately 3 billion base pairs and between 20,000 and 25,000 genes (The Human Genome Project, n.d.). This knowledge has had profound implications for our understanding of human biology, disease, and evolution.

Genetic sequencing has led to the emergence of the field of genomics, which studies the entire set of genes in an organism. Genomics allows scientists to study how genes interact with each other and how they influence an organism's phenotype, or physical characteristics. This research has expanded our understanding of complex traits, such as height and intelligence, which are influenced by many genes working together (Kulkarni & Pfeifer, 2015).

In medicine, genetic sequencing has revolutionized our ability to diagnose and treat disease. Genetic tests can identify mutations associated with certain diseases, allowing for early diagnosis and intervention. For example, women with mutations in certain genes (called BRCA1; BRCA2) have a significantly increased risk of developing breast and ovarian cancer (Mehrgou & Akouchekian, 2016), and genetic testing can identify these women before they develop cancer, enabling preventative measures to be taken.

Figure 7: Errors in the genetic code translated into disease (Unknown, n.d.).

The sequencing of pathogens' genomes has also had profound implications for public health. By sequencing the genomes of viruses, bacteria, and other infectious agents (Ferdinand et al., 2021), scientists can track the spread of diseases, identify new strains, and develop effective treatments and vaccines.

Furthermore, genetic sequencing has revolutionised our understanding of evolution. By comparing the genomes of different species, scientists can trace the evolutionary history of organisms and understand how they have adapted to their environments. This has deepened our understanding of the Tree of Life and has revealed surprising connections between species (Comparative Genomics | Learn Science at Scitable, n.d.).

Conclusion

DNA, the blueprint of life, has revolutionised our understanding of biology. Unraveling its double helix structure was a significant milestone that paved the way for advancements in many fields. The simple yet elegant design of DNA, with its sugar-phosphate backbone and complementary base pairing, facilitates the critical process of DNA replication, thus ensuring the faithful transmission of genetic information from one generation to the next. This information-carrying capacity of DNA makes it the bedrock of heredity, contributing to the diversity of life as we see it. Nucleotide sequences in DNA act as the instructions for the development, functioning, and survival of all known organisms.

The study of DNA has evolved substantially over the past few decades. Techniques such as genetic sequencing have taken our understanding of life to the genetic level, with implications spanning across diverse disciplines. It has opened new avenues in genomics, personalized medicine, evolutionary biology, and more. Moreover, our understanding of DNA has opened the door to personalised medicine. This is a new approach to healthcare that uses information about a person's genetic makeup to tailor their medical treatment. This approach has the potential to increase the effectiveness of treatments and reduce their side effects, improving patient outcomes.

While it was achieved much, the exploration of DNA is far from over. As scientists continue to probe deeper into the world of genetics, every new discovery expands the horizon of possibilities. With each breakthrough, humankind move one step closer to understanding the very essence of life itself.

Bibliographical References

Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2007). Molecular Biology of the Cell. In Molecular Biology of the Cell. W.W. Norton & Company. https://doi.org/10.1201/9780203833445

Berg, P., & Mertz, J. E. (2010). Personal reflections on the origins and emergence of recombinant DNA technology. Genetics, 184(1), 9–17. https://doi.org/10.1534/GENETICS.109.11214

Calladine, C. R., Drew, H. R., Luisi, B. F., & Travers, A. A. (2004). Understanding DNA: The Molecule and How it Works, Third Edition. In Understanding DNA: The Molecule and How it Works, Third Edition. Elsevier. https://doi.org/10.1016/B978-0-12-155089-9.X5000-5

Comparative Genomics | Learn Science at Scitable. (n.d.). Retrieved June 23, 2023, from https://www.nature.com/scitable/knowledge/library/comparative-genomics-13239404/

Cooper, G. M. (2000). Heredity, Genes, and DNA. https://www.ncbi.nlm.nih.gov/books/NBK9944/

Ferdinand, A. S., Kelaher, M., Lane, C. R., da Silva, A. G., Sherry, N. L., Ballard, S. A., Andersson, P., Hoang, T., Denholm, J. T., Easton, M., Howden, B. P., & Williamson, D. A. (2021). An implementation science approach to evaluating pathogen whole genome sequencing in public health. Genome Medicine, 13(1), 1–11. https://doi.org/10.1186/S13073-021-00934-7/TABLES/2

Franklin, R. E., & Gosling, R. G. (1953). Molecular Configuration in Sodium Thymonucleate. Nature 1953 171:4356, 171(4356), 740–741. https://doi.org/10.1038/171740a0

Kulkarni, S., & Pfeifer, J. (2015). Clinical Genomics. A Guide to Clinical Next Generation Sequencing. In Elsevier (1st ed., Vol. 35, Issue 2). Elsevier. Retrieved 21 June, 2023 from http://www.sciencedirect.com:5070/book/9780124047488/clinical-genomics

Manolio, T. A., Chisholm, R. L., Ozenberger, B., Roden, D. M., Williams, M. S., Wilson, R., Bick, D., Bottinger, E. P., Brilliant, M. H., Eng, C., Frazer, K. A., Korf, B., Ledbetter, D. H., Lupski, J. R., Marsh, C., Mrazek, D., Murray, M. F., O’Donnell, P. H., Rader, D. J., … Ginsburg, G. S. (2013). Implementing genomic medicine in the clinic: the future is here. Genetics in Medicine 2013 15:4, 15(4), 258–267. https://doi.org/10.1038/gim.2012.157

Mehrgou, A., & Akouchekian, M. (2016). The importance of BRCA1 and BRCA2 genes' mutations in breast cancer development. Medical Journal of the Islamic Republic of Iran, 30(1), 369.

Mullis, K. B. (1990). The unusual origin of the polymerase chain reaction. Scientific American, 262(4), 56–65. https://doi.org/10.1038/SCIENTIFICAMERICAN0490-56

Roy, S., & Kundu, T. K. (2021). Chemical Biology of the Genome. In Chemical Biology of the Genome. Elsevier. https://doi.org/10.1016/B978-0-12-817644-3.09994-3

The Human Genome Project. (n.d.). Retrieved June 23, 2023, from https://www.genome.gov/human-genome-project

Watson, J. D., & Crick, F. H. C. (1953). Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid. Nature 1953 171:4356, 171(4356), 737–738. https://doi.org/10.1038/171737a0

What is DNA?: MedlinePlus Genetics. (n.d.). Retrieved June 23, 2023, from https://medlineplus.gov/genetics/understanding/basics/dna/

Wilhelm, T., Said, M., & Naim, V. (2020). DNA Replication Stress and Chromosomal Instability: Dangerous Liaisons. Genes, 11(6), 1–35. https://doi.org/10.3390/GENES11060642

Visual Sources