a. The genome is all the genetic material in the organism.

b. The genome is copied and inherited. (Figure 12.1)

c. The genome is a program which guides the composition and operation of the organism.

d. The genome specifies the structures, hence the functions, of proteins in the organism (e.g. sickle-cell hemoglobin, Section 5.12).

e. The genome thus directs the form of the organism.

f. Replication is the process by which a cell copies its genome information for daughter cell descendants.

a. Gregor Mendel, an Austrian monk, carried out pea plant experiments to study heredity.

b. Mendel ran his experiments from 1857 to 1868, and published his results in 1866.

c. Mendel's work was ignored until 1900, less than one hundred years ago.

d. Correns, de Vries, and von Tschermak rediscovered Mendel's rules and recognized Mendel's work circa 1900.

e. "Mendelian inheritance" is guided by two rules:

f. Though Mendel knew nothing of cell division, chromosomes or DNA, it is enlightening to study Mendelian inheritance (see Chapter 16) by including these topics.

a. Thomas Hunt Morgan, using the fruit fly (Drosophila melanogaster) at Columbia University, pioneered modern genetics.

b. The Drosophila (Figure 12.2) fruit fly is an excellent research subject, due to:

c. The wild-type Drosophila is defined as the standard for comparison with variant flies.

d. The source of variant flies (Figure 12.3) was not always understood:

e. The term "mutant" can be used to refer either to the genome or to the individual.

f. A genome contains many distinct bits of information, each specifying a small part of the individual's overall composition.

a. Beadle and Tatum, in the 1940s, linked genetics and metabolism, using Neurospora crassa.

b. A prototroph is an organism that can make all its necessary components from simple ingredients.

c. An auxotroph is an organism that cannot make some cellular component(s) and must have supplements.

d. Beadle and Tatum used auxotrophs to show that biosynthetic pathways are specifically affected by mutations in the genome (Figure 12.4). They showed that:

e. Metabolic pathways can be inferred by assuming "one gene, one enzyme."

f. The gene, enzyme rule is better stated: "one gene, one polypeptide."

g. Sir Archibald Garrod studied human abnormalities he termed "inborn errors of metabolism."

h. Phenylketonuria (PKU) is a disorder caused by the inability to metabolize phenylalanine.

i. Figure 12.5 shows a host of diseases caused by metabolic pathway errors.

a. Though there was agreement that cells carry and pass on the genetic information of heredity, there was disagreement on which cell component carried the information.

b. Frederick Griffith's 1928 observations, of R form Streptococcus being transformed into S form, suggested that the transforming agent also carried the genetic information (Figure 12.6).

c. Avery, MacLeod, and McCarty's 1943 experiments on Streptococcus systematically eliminated each cell component and proved that nucleic acid is the transforming agent, convincing most that DNA is the genetic material.

a. Bacteriophage (literally, bacterium eaters) are viruses that invade bacteria.

b. Viruses (Sections 2.7—2.8 are not cells, but are genome-containing parasitic particles called virions (Figure 12.7).

c. In the 1940s, Delbruck, Luria, and Hershey (the "American phage group") developed methods for using bacteriophage as a genetic model.

d. The "phage group" studied E. coli-invading viruses, and pioneered techniques for growing bacterial cells, and for measuring concentrations (or, titers) of cells and the viruses within them.

e. Figure 12.8 illustrates the dilution and petri plating techniques used to measure bacterial concentrations.

f. This technique uses agar as a growth substrate, and results in visible colonies of cells, all of which are clones, having been produced asexually at the site where they were plated.

g. A turbid culture of E. coli is made clear by the introduction of phage, which lyse the bacteria (Figure 12.9).

h. This gives a technique for counting phage, which, if introduced onto a plate of bacteria, will make circular areas of cell lysis, called plaque; at a given dilution, each phage makes one plaque .

i. Different phage types have been given abbreviated names (e.g. T2, SP01), and each is distinctive according to the shape and size of its plaque.

j. Each phage virion particle has a distinctive size and shape (Figure 12.10).

a. Pure phage cultures, when incubated with host cells, show a definite pattern of multiplication (Figure 12.11).

b. The pattern shows a period of no increase in phage-forming units, the eclipse period. This period occurs as phage attach to (Figure 12.12) and invade the host cells, and produce phage components which are not yet assembled into new particles.

c. The next period shows rapid multiplication and growth of the phage culture, as new particles are assembled. The host cell eventually ruptures due to the phage invasion, releasing more phage into the culture.

d. Hershey and Chase, in 1951, used radioactive labeling to show that only the DNA component of the phage enters the host cell, as the protein component remains on the host cell surface (Figure 12.13).

e. These experiments demonstrated that only the phage DNA is passed to the next generation of phage, confirming that DNA (not protein) carries the genetic information.

f. Figure 12.14 summarizes a cycle of phage multiplication.

g. Viruses have evolved with their hosts, and are members of the ecological community of most organisms.

h. Virus-infected cells can serve as useful genetic models, as the small, easy to manipulate viral genome replaces the host genome.

a. DNA is a polymer made of four types of nucleotide monomers.

b. Each nucleotide consists of a phosphate, the sugar deoxyribose, and one of four kinds of bases.

c. The bases thymine (Thy) and cytosine (Cyt) are pyrimidines, which have one ring of C and N atoms. The bases adenine (Ade) and guanine (Gua) are purines, which have a double-ring structure.

d. One nucleic acid molecule is made of nucleotides in a sugar-phosphate backbone, with each phosphate connecting the 5' carbon of one sugar to the 3' carbon of the next sugar.

e. Nucleic acid sequences are conventionally written in 5' to 3' direction, where the prime marks indicate carbon atoms of sugars, as opposed to those of bases.

f. In 1951, James Watson and Francis Crick, using X-ray photographs taken by Rosalind Franklin and Maurice Wilkins (e.g. Figure 12.15) deduced the double-helix structure of DNA (Figure 12.16).

g. The Watson-Crick model shows that DNA is composed of two polynucleotide strands with opposite 5'-3' polarities.

h. Sidebar 12.1 addresses the question of whether nucleic acids replicate themselves, and points out that the molecule itself cannot replicate without the help of an enzymatic apparatus.

a. As Watson and Crick suggested, the double-helix structure of DNA's complementary nucleotide strands suggests a replication process (Figure 12.17):

b. The DNA replication process is a polymerization that is catalyzed by a DNA polymerase.

c. Section 13.4 addresses the mechanism of DNA replication.

a. The Hershey—Chase and Beadle—Tatum experiments established that a genome, consisting of genes that specify one polypeptide each, specifies protein structures.

b. Genomes are long DNA molecules: several million nucleotide pairs divided into a few thousand genes.

c. A nucleic acid genome encodes a genetic message from its four "letters," the four nucleotides, and is analogous to the Morse code (combinations of dot, dash, space) encoding an English language message.

d. A DNA sequence encodes (or translates into)an amino acid sequence, which is the primary structure of a protein (see Chapter 14).

e. Proteins fold into the correct three-dimensional shape largely based on the lowest energy state they can achieve from their primary structure, but also assisted by chaperonins in the cell.

f. Enzymes, which are all proteins, synthesize the non-protein components of the cell, and these structures and other proteins form larger cellular components.

g. This assembly happens spontaneously, with little or no additional information from the genome.

h. Section 4.11 covers Anfinsen's experiments on protein structure.

a. Any change in a nucleic acid sequence can change the encoded message and is known as a mutation.

b. These general types of mutations can occur:

c. With regard to nucleotide structure, the following types of mutations are known:

d. Chapter 17 covers the causes of mutations.