Author: Xinyao Ma
Editors: Emily Yu, Junyu Zheng
Artist: Sally Sun
DNA, or deoxyribonucleic acid, plays a pivotal role in today's science across various disciplines. Its unique structure and genetic code serve as the blueprint for all living organisms, determining traits, functions, and behaviors. In fields such as genomics, molecular biology, and biotechnology, DNA is essential for understanding diseases' heredity, evolution, and pathogenesis. The ability to sequence and manipulate DNA has revolutionized medical research, leading to advancements in personalized medicine, gene therapy, and genetic engineering while also bringing the field of pharmacogenomics into light. Moreover, DNA analysis has become a cornerstone of forensic science, aiding scientists by providing crucial evidence in criminal investigations and identifying individuals with unparalleled accuracy. DNA's significance in modern science lies in its capacity to unlock the mysteries of life, drive innovation, and shape the future of healthcare, agriculture, and beyond.
DNA is the molecule that carries genetic information for the development and functioning of an organism. A DNA molecule is typically found in its iconic double-stranded structure, as Rosalind Franklin, James Watson, and Francis Crick discovered. There are three different DNA helix forms—A-form, B-form, and Z-form, each characterized by distinct physical structural characteristics:
A form: right-hand double helix, similar to B-form DNA, but with 11 base pairs per turn and generally wider.
B form: the most commonly occurring DNA type characterized by right-hand plectonemic coiling with about 10 base pairs per turn and distinct minor and major grooves.
Z-form: left-hand double helix with minor and major grooves similar to the B form. It also has a repeating structure. They are transient and only exist during certain biological activities.
The double DNA helix comprises two separate DNA strands joined by A-T and C-G complementary base pairings. These DNA chains are polymers, massive biomolecules composed of smaller subunits called nucleotides. Nucleotides typically have the following substituents: a pentose called deoxyribose, a phosphate group, and a nitrogenous base (either Adenine, Cytosine, Thymine, or Guanine).
Throughout the years, the collaborative efforts of scientists have progressed our knowledge of DNA. However, Friedrich Miescher’s initial isolation of DNA set the stage for discoveries like Franklin’s double-helix structure. In 1869, Miescher isolated DNA from lymphoid cells, discovering the existence of DNA, developing the first extraction techniques, and determining its chemical composition, though its significance was not fully understood at the time. In 1919, Russian physicist-chemist Phoebus Levene successfully determined the composition of nucleotides, the monomer building blocks of DNA. In the early 1950s, Chargaff proposed a rule (Chargaff’s rule) describing the numerical relationship between pyrimidine and purine bases. James Watson and Francis Crick famously proposed the double helix structure of DNA (B-DNA), building upon the X-ray diffraction work of Rosalind Franklin and Maurice Wilkins (Watson & Crick, 1953). This groundbreaking discovery revolutionized the field of genetics and laid the foundation for modern molecular biology.
DNA is responsible for carrying genetic information, which cells use to synthesize RNA and, subsequently, proteins. These proteins fulfill multiple functions in various life processes. This process (DNA-RNA-protein) is sometimes referred to as the central dogma.
Throughout the years, many DNA methods have been utilized in research. Multiple DNA extraction and in vitro replication and synthesis methods have been developed, including Polymerase Chain Reaction, Loop-Mediated Isothermal Amplification (LAMP), Golden Gate Assembly, Gibson Assembly, and Rolling Circle Amplification. Moreover, numerous sequencing methods have been used, including nanopore DNA sequencing, Sanger sequencing, and Next Generation Sequencing.
These technologies have already been used in research scenarios, primarily in molecular biology, cellular biology, evolutionary biology, developmental biology, and genetic engineering, but are also in emerging fields such as pharmacogenomics and synthetic biology. Notably, the Human Genome Project (HGP) employed multiple sequencing methods to map a complete human genome, which could be used later in genomic analysis.
Genetic editing tools such as the CRISPR-Cas system have also been utilized in multiple fields, notably genetically modified crops. Synthesis technologies have been used in conjunction to insert novel sequences into model organisms to realize new functions such as biochemical production and medical treatments.
Nowadays, DNA technologies are being incorporated into more and more disciplines beyond the field of conventional natural science. Forensic science is one field where novel DNA technologies actively enhance its development and real-life application.
DNA technologies involved in forensics primarily include extraction and sequencing methods. DNA extracted from crime scene materials is commonly compared with the DNA profile of one or multiple suspects to identify the prime suspect. Amplification techniques such as PCR exponentially replicate the extracted evidence DNA.
DNA technologies generally have high fidelity. PCR has an error rate of 3-6 per 306 bases, while Sanger Sequencing accuracy is around 99.99%. Moreover, DNA testing and comparison provide a concrete and objective method for forensic investigation, and while it’s not infallible, forensic DNA analysis is estimated to be around 95% accurate. DNA analysis has already been used to solve several cold cases, including a mis-convicted 1978 double-murder case, the Golden State Killer (1975-86) case, a 1956 Sexual Assault and Murders case, and multiple other cases primarily concerning murders or sexual assaults (since normally more DNA-containing materials could be present in such cases).
DNA technologies offer great promise for application in various fields, including medicine, genomics, evolutionary/developmental biology, biomedical engineering, forensics, and synthetic biology. Application in forensics has already achieved notable results, helping solve multiple decade-old cold cases, clearing the names of those falsely convicted, and delivering due justice. Scientists should continue to increase the accuracy and reliability of DNA profiling technologies to better safeguard and uphold criminal justice through forensic DNA analysis.
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