STRUCTURE OF DNA MOLECULE

Although scientists as far back in history as Aristotle recognized that the features of one generation are passed on to the next (...like begets like...) it was not until the 1860's that the fundamental principles of genetic inheritance were described by Gregor Mendel. Mendel's work with common garden peas, pisum sativum, led him to hypothesize that phenotypic traits (physical characteristics) are the result of the interaction of discrete particles, which we now call genes, and that both parents provide particles which make up the characteristics of the offspring. His theories were, however, widely disregarded by scientists of the time. In the last quarter of the 19th century, however, microscopists and cytologists, interested in the process of cell division, developed both the equipment and the methods needed to visualize chromosomes and their division in the processes of mitosis (A. Schneider, 1873) and of meiosis (E. Beneden, 1883).

As the 20th century began many scientists noticed similarities in the theoretical behavior of Mendel's particles, and the visible behavior of the newly discovered chromosomes. It wasn't long before most scientists were convinced that the hereditary material responsible for giving living things their characteristic traits, and chromosomes must be one in the same. Yet, questions still remained. Chemical analysis of chromosomes showed them to be composed of both protein and DNA. Which substance carried the hereditary information? For many years most scientists favored the hypothesis that protein was the responsible molecule because of its comparative complexity when compared with DNA. After all, DNA is composed of a mere 4 subunits while protein is composed of 20, and DNA molecules are linear while proteins range from linear to multiply branched to globular. It appeared clear that the relatively simple structure of a DNA molecule could not carry all of the genetic information needed to account for the richly varied life in the world around us!

It was not until the late 1940's and early 1950's that most biologists accepted the evidence showing that DNA must be the chromosomal component that carries hereditary information. One of the most convincing experiments was that of Alfred Hershey and Martha Chase who, in 1952, used radioactive labeling to reach this conclusion(See Graphics). This team of biologists grew a particular type of phage, known as T2, in the presence of two different radioactive labels so that the phage DNA incorporated radioactive phosphorus (32P), while the protein incorporated radioactive sulfur (35S). They then allowed the labeled phage particles to infect non-radioactive bacteria and asked a very simple question: which label would they find associated with the infected cell? Their analysis showed that most of the 32P-label was found inside of the cell, while most of the 35S was found outside. This suggested to them that the proteins of the T2 phage remained outside of the newly infected bacterium while the phage-derived DNA was injected into the cell. They then showed that the phage derived DNA caused the infected cells to produce new phage particles. This elegant work showed, conclusively, that DNA is the molecule which holds genetic information. Meanwhile, much of the scientific world was asking questions about the physical structure of the DNA molecule, and the relationship of that structure to its complex functioning.