Unit Three. The Continuity of Life
The realization that patterns of heredity can be explained by the segregation of chromosomes in meiosis raised a question that occupied biologists for over 50 years: What is the exact nature of the connection between hereditary traits and chromosomes?
In this chapter you will examine some of the chain of experiments that have led to our current understanding of the molecular mechanisms of heredity. The experiments determining that DNA is the genetic material are among the most elegant in science. Just as in a good detective story, each conclusion has led to new questions. The intellectual path taken has not always been a straight one, the best questions not always obvious. But however erratic and lurching the course of the experimental journey, our picture of heredity has become progressively clearer, the image more sharply defined. We now understand in considerable detail how the DNA molecule copies itself, and how changes to it lead to hereditary gene mutations.
11.1. The Discovery of Transformation
As we learned in chapters 8, 9, and 10, chromosomes contain genes, which, in turn, contain hereditary information. However, Mendel’s work left a key question unanswered: What is a gene? When biologists began to examine chromosomes in their search for genes, they soon learned that chromosomes are made of two kinds of macromolecules, both of which you encountered in chapter 3: proteins (long chains of amino acid subunits linked together in a string) and DNA (deoxyribonucleic acid—long chains of nucleotide subunits linked together in a string). It was possible to imagine that either of the two was the stuff that genes are made of—information might be stored in a sequence of different amino acids, or in a sequence of different nucleotides. But which one is the stuff of genes, protein or DNA? This question was answered clearly in a variety of different experiments, all of which shared the same basic design: If you separate the DNA in an individual’s chromosomes from the protein, which of the two materials is able to change another individual’s genes?
In 1928, British microbiologist Frederick Griffith made a series of unexpected observations while experimenting with pathogenic (disease-causing) bacteria. Figure 11.1 takes you stepwise through his discoveries. When he infected mice with a virulent strain of Streptococcus pneumoniae bacteria (then known as Pneumococcus), the mice died of blood poisoning, as you can see in panel 1. However, when he infected similar mice with a mutant strain of S. pneumoniae that lacked the virulent strain’s polysaccharide capsule, the mice showed no ill effects, as you can see in panel 2. The capsule was apparently necessary for infection. The normal pathogenic form of this bacterium is referred to as the S form because it forms smooth colonies in a culture dish. The mutant form, which lacks an enzyme needed to manufacture the polysaccharide capsule, is called the R form because it forms rough colonies.
Figure 11.1. How Griffith discovered transformation.
Transformation, the movement of a gene from one organism to another, provided some of the key evidence that DNA is the genetic material. Griffith found that extracts of dead pathogenic strains of the bacterium Streptococcus pneumoniae can "transform" live harmless strains into live pathogenic strains.
To determine whether the polysaccharide capsule itself had a toxic effect, Griffith injected dead bacteria of the virulent S strain into mice and as panel 3 shows, the mice remained perfectly healthy. Finally, as shown in panel 4, he injected mice with a mixture containing dead S bacteria of the virulent strain and live, capsuleless R bacteria, each of which by itself did not harm the mice. Unexpectedly, the mice developed disease symptoms and many of them died. The blood of the dead mice was found to contain high levels of live, virulent Streptococcus type S bacteria, which had surface proteins characteristic of the live (previously R) strain. Somehow, the information specifying the polysaccharide capsule had passed from the dead, virulent S bacteria to the live, capsuleless R bacteria in the mixture, permanently transforming the capsuleless R bacteria into the virulent S variety.
Key Learning Outcome 11.1. Hereditary information can pass from dead cells to living ones and transform them.