Course: SAT 170 Introductory Biotechnology

Unit 3 Reading and Multimedia Assignment

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DNA in Bacteria

After much research, it was found that genetic information was carried by DNA and that genes are the functional units of heredity.

Early Investigations into Heredity

Gregor Mendel's experimental work and his concept of discrete hereditary factors were rediscovered by scientists in the early 1900s. Danish botanist Wilhelm Johannsen coined the word "gene" ("gen" in Danish and German) in 1909 to describe the fundamental physical and functional units of heredity. The related word genetics was first used by William Bateson in 1905.

In 1910, Thomas Hunt Morgan showed that genes reside on specific chromosomes. Using fruit flies (Drosophila melanogaster) as a model organism, Morgan and his group at Columbia University later showed that genes, strung on chromosomes at specific locations, are the units of heredity. With this knowledge, Morgan and his students began the first chromosomal map of the fruit fly. Morgan and his students made many important contributions to genetics. They showed that chromosomes carry genes, discovered genetic linkage (the fact that genes are arrayed on linear chromosomes), and described chromosome recombination.

Morgan made the study of heredity in fruit flies very popular during the early 1900s, but the first evidence of transfer (inheritance) of genetic traits via DNA came from studies with bacteria and viruses that only infect bacteria.

Griffith's Experiment

In 1928 Frederick Griffith showed that genes could be transferred. In what is now known as Griffith's Experiment, he injected a deadly strain of bacteria that had been heat-killed into a mouse. This transferred genetic information from the deadly strain to a non-virulent strain of the same bacteria, thus killing the mouse.

Griffith was trying to create a pneumonia vaccine and was working with different strains of Streptococcus pneumoniae bacteria. He had discovered that he could convert the non-pathogenic R (rough colony) strain into the virulent S (smooth encapsulated colony) strain. After he injected mice with R strain cells and, simultaneously, with heat-killed cells of the S strain, the mice developed pneumonia and died (see figure above). In their blood, Griffith found live bacteria of the deadly S type. The S strain extract had "transformed" the R strain bacteria into the S form. In addition, all of the offspring of the newly transformed strain retained the S-type pathogenicity.

Griffith called this phenomenon "transformation," a term we now use to describe the genotypic and phenotypic alteration of a cell resulting from the direct uptake, incorporation, and expression of exogenous genetic material (DNA) from the surroundings.

The Role of DNA in Transformation

Bacteriologists suspected that Griffith's transforming factor was some kind of protein. The transforming principle could be precipitated with alcohol, which showed that the factor was not a carbohydrate like the polysaccharide coat itself. At the time, biochemists had assumed that deoxyribonucleic acid (DNA) was a relatively unimportant structural chemical in chromosomes and that proteins, with their greater chemical complexity, transmitted genetic traits.

However, in 1944 Oswald Avery, Colin MacLeod, and Maclyn McCarty published a paper showing that DNA was the substance that causes bacterial transformation. Their paper was the culmination of research done in the 1930s and early 1940s at the Rockefeller Institute for Medical Research which intended to show how to purify and characterize the "transforming principle" responsible for the transformation phenomenon first described in Griffith's experiment of 1928.

Using an extract of bacterial cells in vitro, Avery's group observed that proteases or enzymes, which degrade proteins, did not destroy the transforming principle. Neither did lipases, the enzymes that digest lipids. They found that the transforming substance was rich in nucleic acids. Yet ribonuclease, which digests RNA, did not inactivate the substance. They also found that the transforming principle had a high molecular weight. Treating the extracts with deoxyribonuclease to destroy the DNA in them abolished their transforming activity. They concluded that DNA was the substance of genes; it was the only agent that could produce an enduring, heritable change (transformation) in an organism.

The results of Avery group's experiments were at first skeptically received by the scientific community because of the belief that protein probably was the genetic factor. It was not until the development of genetic markers and the discovery of other methods of genetic transfer (conjugation in 1947 and transduction in 1953) by Joshua Lederberg that Avery's experiments were accepted.