DNA (deoxyribonucleic acid) is a fascinating and compelling molecule that is responsible for expressing, storing, and replicating all of the genetic information in eukaryotic (nucleated) cells. This marvelous molecule is nothing less than a chemical history of all living things on our planet; its span extends throughout organic time and contains chemical documentation of the course of evolution in all species.
In 1857, Gregor Mendel (1822-1884), an Austrian monk and biologist, was the first to illustrate that inheritable characteristics (such as height and color) were distributed from parent to offspring in a mathematically predictable pattern. He did these experiments using pea plants. As he analyzed his results, he noted that each character had variations (such as tall or small, and purple or white) that again were expressed in a mathematically predictable pattern. These predictable patterns could be expressed graphically. (Later, British geneticist Reginald Punnett arranged such patterns of inheritance in grids, which are now referred to as “Punnett squares”). Mendel's work stimulated much interest in the study of genetics; as a result of his work, he is known as the father of genetics.
Mendel had illustrated that characteristics are inherited through particles in a predictable fashion, but how does this happen? In 1928, biologist Frederick Griffith theorized that a molecule for inheritance must exist. His experiments involved injecting virulent and nonvirulent strains of bacteria into mice. These experiments never assisted Griffith in his quest to discover the inheritance molecule, but they did prove that a characteristic (in this case virulence) could be passed on from one type of bacteria (which was virulent) to another type of bacteria (which originally was not virulent). He called this “transformation.” Griffith's research on transformation proved that an inheritance molecule existed.
During this time, there were two prevalent theories on what the inheritance molecule was. The first theory was that it was a protein, which was a popular candidate because there were 20 amino acids. The second theory was DNA, which was a less popular theory because it was composed of only four nucleotides and because scientists could not yet conceive how a molecule composed of only four types of nucleotides could account for the complexity of an organism. Some theories proposed that other proteins were the inheritance molecules.
Fourteen years later, a scientist named Oswald Avery attempted to identify the inheritance molecule based on Griffith's findings. In Avery's experiments, he used the same types of bacteria from Griffith's work. However, with newer technology and a deeper understanding of the knowledge of cellular biology and structure, he was able to use a different approach. Avery decided to selectively destroy different types of molecules (e.g., carbohydrates, proteins, lipids, and ribonucleic acids) in the virulent bacteria. He then administered the samples to mice to test for virulence. The results showed that all the bacteria maintained their virulence except for the bacteria whose ribonucleic acids were destroyed. Avery had identified the inheritance molecule, which was composed of nucleic acids: DNA.
Even though Avery had clearly illustrated that DNA was the molecule of inheritance, most scientists at that time rejected the idea. Many still found it too perplexing to understand how a very uniform molecule was responsible for the advent of something as complicated as a human being. In addition, this began to raise eyebrows in religious circles that a molecule, and not direct action by God, was at the root of an individual's inherited characteristics.
It took almost 90 years from Mendel's illustration that characteristics were passed on from parent to offspring in a predictable pattern to the idea that DNA, a molecule, was solely responsible for the occurrence of genetic diversity among all species. However, at this time, no one knew what DNA was—neither its structure nor how it worked.
In 1953, biologists James Watson and Francis Crick, working in Cambridge, United Kingdom, accurately proposed a working model of the structure of DNA. They were able to do this based on results from two very important works. The first important work was research done by Erwin Chargaff, in which he proved that the DNA molecule was composed of four nucleotide bases: adenine (A), guanine (G), cytosine (C), and thy-mine (T). He demonstrated that adenine and thy-mine occurred in equal amounts, as did guanine and cytosine. Based on these findings, he postulated that adenine paired with thymine (A=T) and that guanine paired with cytosine (G=C).
The second important work that assisted Watson and Crick was the photography of X-ray diffraction patterns of crystallized DNA, which were completed by Rosalind Franklin and Maurice Wilkins. Their research showed that the DNA molecule had a helical shape made up of two strands connected by ladder-like rungs.
Based on these two studies, Watson and Crick proposed that the DNA molecule was a double-stranded helix and that those two strands were made of a sugar-phosphate backbone. They also concluded that the “ladder-like rungs” that were holding the two strands together were alternated A=T and G=C pairs. Watson and Crick were also able to utilize current molecular knowledge to discover that the reason why adenine and guanine paired together was because they both had two available hydrogen bonds, and the reason why guanine and cytosine paired together was because they each had three available hydrogen bonds. They proposed that because one of the DNA strands was an opposite complement to the other (because of the pairing bases), the DNA molecule was composed of two “antiparallel” strands.
Now the inheritance molecule was identified, and a structure of its model was established. This changed the way scientists viewed genetics and heredity. The next perplexing questions were How does this molecule replicate itself? and How does it work to make a cell or an organism?
At this time it was generally accepted that DNA must replicate itself in order to reproduce new cells and for organisms to produce new offspring. In 1958, Matthew Meselson and Franklin Stahl utilized research involving radio-labeled nitrogen bases (which are what A, T, G, and C are composed of) to demonstrate that DNA replicated itself using what is known as a semi-conservative model. This model helped to illustrate that the two strands of DNA actually unzip, and one of the DNA strands serves as a template to reproduce another strand of DNA by pairing nucleotides. The template and new strand of DNA are separated, the original strands of DNA are reconnected (or zipped back together), and the newly created strand has a complementary strand attached (using Chargaff's rule) to it in place of the original template. This replication of DNA happens during cell replication, a process in which a cell makes a copy of itself, DNA and all. However, it must be noted that a cell cannot replicate an infinite number of times. A cell can undergo cell replication only a limited number of times while maintained in tissue culture; this phenomenon was illustrated in 1965 by Leonard Hayflick and was called the “Hayflick limit.”
Besides replication, the DNA molecule is responsible for storing the information necessary to synthesize the basic building blocks called amino acids. There are 20 amino acids, which in different combinations make up proteins, enzymes, and other constituents that compose all cells and organisms. The DNA molecule achieves this by a process called transcription. During transcription, the DNA molecule unzips a small portion of itself and a messenger RNA (mRNA) molecule is made. This mRNA molecule will ultimately assist in the production of a protein molecule, a process called translation. Therefore what types of proteins are produced is determined by all the different sequences of DNA. These proteins are the basic building blocks for the cell's structure and organ-elles. The same cells conglomerate to form tissues, which become structured organs that can form organ systems. The organ systems (such as the digestive system and the skeletal system) are what make more complicated organisms, like human beings.
The DNA molecule exists today as a product of time. It is responsible for organic diversity and genetic evolution, in addition to accumulating and accelerating all human evolution. In the year 2000, after almost 10 years of research known as the Human Genome Project, scientists completed analyzing more than 3 billion chemical “letters” that make up all human DNA (which is referred to as the human genome code). This accomplishment will eventually revolutionize the diagnosing and treatment of disease and is one of the greatest scientific milestones. The concept of inheritance and what makes up all organisms has changed over time. This began as the idea of an inheritance molecule and evolved into attempting to understand and decipher the vast complexities of the DNA molecule, a task in where we are only just scratching the surface.
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