1.1 A substance that carries hereditary change #
1.1.1 Griffith: transformation of pneumococci #
In 1928 Griffith worked with Streptococcus pneumoniae and mice. Smooth (S) cells make a capsule and are virulent.
A heat-stable substance had transferred a heritable trait. Griffith called the process transformation. He did not identify the molecule. It does not show that the carrier is DNA.
1.1.2 Avery, MacLeod, and McCarty: the transforming principle is DNA #
Avery, MacLeod, and McCarty (1944) fractionated the transforming principle and treated it with enzymes. Proteases did not destroy activity.
The result was resisted for two reasons that belong to the argument. Preparations can contain a trace of protein, and protein was the favoured candidate because it is chemically varied. Those equalities are the pairing rule of Chapter 2.
1.1.3 Hershey and Chase: the phage experiment #
Hershey and Chase (1952) used phage T2, which contains only DNA and protein. Phosphorus is in DNA and essentially absent from protein. They labelled DNA with 32P and protein with 35S, allowed adsorption to Escherichia coli, and sheared empty coats off the cells in a blender.
Most of the 32P entered the cells and appeared in progeny phage. Most of the 35S stayed outside. Separation was not absolute, so the result is a strong enrichment rather than a perfect sort. DNA, not protein, is the genetic material of this phage. Hershey and Chase never purified a chromosome: the virus injected one substance and left the other outside.
1.2 RNA genomes #
1.2.1 The exception, and what it does not overturn #
Some viruses use RNA as the genome that enters the cell. Purified RNA of tobacco mosaic virus is infectious, and reconstitution experiments show that the RNA, not the coat, determines the strain.
The general statement is about nucleic acid, not about deoxyribose. Protein is not the stored genome. Reverse transcription copies RNA into DNA; it does not copy a protein sequence back into a nucleic acid. Here they only fix the rule.
1.3 DNA versus RNA, only as replication needs it #
The study of DNA versus RNA, only as replication needs it provides fundamental principles governing cellular architecture, molecular interactions, and physiological regulation.
Dna Replication
1.3.1 The differences later chapters actually use #
Biochemistry owns the ring structures, the glycosidic bond, and the sugars. Four consequences are used below.
Both polymers are unbranched chains joined by 3′–5′ phosphodiester bonds, each with a 5′ end and a 3′ end. Enzymes that make nucleic acids add the next nucleotide to a 3′-OH, so synthesis runs 5′→3′. That fact forces the lagging strand in Chapter 4 and the direction of transcription in Chapter 6.
DNA contains 2′-deoxyribose. RNA contains ribose, and the 2′-OH makes RNA easier to hydrolyse and able to catalyse, which is why splicing and peptide-bond formation can be ribozyme reactions (Chapters 7 and 8). If uracil were a normal DNA base, repair could not distinguish a damaged cytosine from a legitimate base, so thymine makes uracil in DNA visible as damage (Chapter 5). This is the usual selective explanation, not a second blender experiment.
1.4 Key terms, summary, and self-check #
Key terms. Transformation; transforming principle; Chargaff’s rules; 32P and 35S; central dogma; 2′-OH; thymine; polarity.
Summary. Griffith showed that a heat-stable substance from dead pneumococci carries a heritable trait. Avery, MacLeod, and McCarty identified it as DNA, and Chargaff’s equalities made DNA chemically credible. Hershey and Chase showed that T2 injects DNA and leaves its protein outside. Some viral genomes are RNA, so the rule is nucleic acid, not DNA alone, and reverse transcription does not break the central dogma. DNA is the stabler archive because it lacks a 2′-OH and because thymine marks deaminated cytosine as damage. Chains are polar, and synthesis runs 5′→3′.
Self-check.
1. What did Griffith demonstrate, and which molecule did he not identify?
2. Which enzyme destroyed transformation, and why was the result still disputed?
3. Why were phosphorus and sulfur the right labels for Hershey and Chase?
4. Which observation shows that RNA can be genetic material, and how does a retrovirus differ from tobacco mosaic virus?
5. Why is uracil treated as damage in DNA but not in RNA?
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