DNA sequencing history stretches back to the 1860s when Swiss zoologist Friedrich Miescher first isolated DNA and realized it could reveal clues about hereditary traits in organisms. Although DNA sequencing in biology took time to develop, the modern era of genetic sequencing began with significant strides forward in the 1950s. The modern era of gene sequencing also includes discovering DNA’s double-helix structure by James Watson and Francis Crick in 1953 and the development of polymerase chain reaction (PCR) technology by Kary Mullis in 1983. Here are seven crucial milestones in the history of DNA sequencing.

• Watson and Crick’s Model: The Discovery of DNA and Base Pairs A, C, T, G Base 1953

An essential part of dna history was a DNA sequencing milestone in 1953 when James Watson and Francis Crick proposed a three-dimensional model for DNA. In their findings, they explained that DNA consisted of two strands: one strand containing four bases (adenine, guanine, cytosine, and thymine) that each pair with a different strand base (thymine pairs with adenine; guanine pairs with cytosine). Their model demonstrated how these paired bases would line up and allow replication of genes.

• Friedrick Sanger’s Technique: First DNA Sequencing Using Radiolabelled Fragments

 Biochemist Fred Sanger published his DNA sequencing technique soon after. Rather than getting an entire sequence at once, Sanger divided it into smaller segments he could put together later, like pieces of a puzzle, called the Chain Termination method. The method worked well for Sanger, who received a Nobel Prize for his research on RNA in 1993. However, the method took significant computing power to process genetic information using computers at that time, rendering many labs unable to use his technique until more powerful machines became available years later.

• Fredrick Sanger First Complete Genome of Bacteriophage, 1977

In 1977, Frederick Sanger and his team at Britain’s Medical Research Council Laboratory of Molecular Biology (MRC LMB) published a paper announcing that they had completed sequencing an entire genome: phage φX174. Phage φX174 is a strand of DNA that infects bacteria and makes them burst; scientists have used it to learn how DNA functions for centuries. 

The virus they chose to sequence was small enough to fit on one slide, but it also happened to contain long stretches of repetitive DNA that made it ideal for sequencing by Sanger’s method. The success in sequencing a virus spurred Sanger and his team to begin work on the bacterial genome; their first bacteria target was Haemophilus influenza. Sanger won two Nobel Prizes for his DNA sequencing methods and sequencing insulin.

• First Draft Of A Whole Human Genome, 2001

In 2001, scientists finished sequencing a complete human genome. It was a monumental achievement and an essential milestone in DNA sequencing history. The project took 13 years and cost $3 billion to complete. What’s more, it required supercomputers processing at five gigabytes per second. It’s remarkable to think that just 17 years later, you can get your whole genome sequenced for around $1,000 in less than two weeks—and without supercomputers. DNA sequencing has made incredible progress since 2001.

• The Identification of Promoter Sequences in DNA

Arthur Kornberg first identified promoter sequences in DNA while studying what causes genes transcription. Kornberg discovered the sequence promoters after mixing bacterial DNA with viral DNA and isolating RNA. The discovery showed that sections of DNA regulate when gene transcription takes place. Since then, scientists have found these sequences essential for an organism as they can help determine which genes are turned on or off during development or growth.

However, it’s crucial to note that promoters must be located upstream from a gene because their signals tell cells where transcription should begin. Transcription is vital because a cell would not have any way to read its DNA without transcription. Thus, we wouldn’t know how to create proteins or make copies of our genetic material. With that said, the identification of promoter sequences has helped us better understand how genes function within organisms’ genomes.

• First Sequencing Technology Platform, Fritz Pohl, 1984

In 1984, Fritz Pohl and his team developed a method for sequencing long fragments of DNA using pulsed-field gel electrophoresis. Pohl created a new technology platform that involved fragmenting DNA with restriction enzymes to sequence larger pieces. The technique involved separating sequence enzymes on a gel, then visualizing and mapping individual fragments through autoradiography.

Although his technique was revolutionary, Pohl’s work could not help to produce complete genome sequences, as it required large amounts of starting material. The success of Sanger’s sequencing methodology ultimately led to Pohl abandoning research into DNA sequencing and moving onto other projects within biotechnology.

• Next Generation: Pyrosequencing, Mostafa Ronaghi, Mathias Uhlen, and Pȧl Nyŕen,1996

Pyrosequencing is a technique for sequencing DNA. It’s a solid-phase, bead-based method that allows automated DNA sequencing and is based on thermal cycling using four different dideoxynucleotides (ddNTPs) labeled with unique infrared fluorophores. This technology has dramatically improved sequencing efficiency and significantly reduced costs compared to other DNA sequencing technologies.

Pyrosequencing is a type of sequencing that uses polymerase chain reaction (PCR) to generate DNA sequences from single-stranded templates, which Dr. Paul Rothemund patented in 1996. Pyrosequencing can help determine longer stretches of DNA inexpensively and is particularly suited for high throughput applications such as next-generation sequencing. While pyrosequencers have not reached commercialization, their technology paved the way for subsequent sequencing methods.

• The 454 system- The First ‘Next-Generation’ Sequencing Platform In The Market

In 2005, The 454 system became available. 454’s first sequencer, which could handle only two megabases (Mb) of DNA at a time, sold for $400,000. While it was limited compared to today’s equipment and hard to use on its own, you would need two weeks of training to run it. It provided a crucial proof-of-concept that sequencing systems could be commercially viable.

Finally, it motivated both academics and companies to speed up their efforts. If other groups were going to beat them to market with next-generation sequencers, they needed to get cracking!

• Modern DNA Sequence Optimization Techniques; Third-Generation Sequencing Techniques

Third-generation sequencing is faster, more accurate, and more accessible than ever. The new technology offers researchers numerous advantages that could transform biological research as we know it. Here are seven crucial milestones in third-generation sequencing’s history that have helped bring us to where we are today.

Modern sequencing involves a lot more than extracting DNA from your cells, cutting it up into smaller chunks, and running it through a massive slab of chemicals to determine what’s inside. Today, researchers use many computer methods to try and optimize their sequencing process so they can analyze more significant quantities of information faster and more efficiently.

Solexa/Illumina-2007 NGS Technology: One of the most modern processes currently available for genome sequencing. With machines such as these utilizing NGS technology, it’s possible to generate new DNA sequences in 24 hours with accuracy rates between 80% and 99%.

SOLiD System: In contrast to Solexa/Illumina’s 96-well plate setup, which requires you to perform multiple steps across several plates at once—the HiSeq 2500 uses a single 384-well sample-in-one-tube method. Other third-generation sequencing techniques include;

Conclusion

DNA sequencing is a significant scientific achievement that has shaped our world. Without it, we wouldn’t have many of our modern inventions. What’s more, its influence will only grow as scientists learn to read genomes with increasing speed and accuracy. Scientists expect to sequence millions—or billions—of genomes over the next decade or two. PacBio RS DNA sequencing identified mutations that enabled researchers to create high-performing vaccines for viruses like Dengue and Hepatitis C. As demand for single-molecule DNA sequencing continues to grow, research efforts will aim to improve these promising technologies. The possibilities are endless! So get out there and explore genetics; who knows what kinds of amazing things you might reveal.