Chapter 16 The Molecular Basis of Inheritanc e
Overview: Life’s Operating Instructions
• In April 1953, James Watson and Francis Crick shook the scientific
world with an elegant double-helical model for the structure of
deoxyribonucleic acid, or DNA.
• Your genetic endowment is the DNA you inherited from your
• Nucleic acids are unique in their ability to direct their own
• Tprecise replication of DNA and its transmission from onethe
generation to the next.
• Ibiochemical, anatomical, physiological, and (to some extent)
Concept 16.1 DNA is the genetic material
The search for genetic material led to DNA.
• Once T. H. Morgan’s group showed that genes are located on
chromosomes, the two constituents of chromosomes—proteins
and DNA—were the candidates for the genetic material.
• Until the 1940s, the great heterogeneity and specificity of function
of proteins seemed to indicate that proteins were the genetic
• However, this was not consistent with experiments with
microorganisms, such as bacteria and viruses.
• The discovery of the genetic role of DNA began with research by
Frederick Griffith in 1928.
• Hpneumonia in mammals.us pneumoniae, a bacterium that causes
One strain, the R strain, was harmless.
The other strain, the S strain, was pathogenic.
• Griffith mixed heat-killed S strain with live R strain bacteria and
injected this into a mouse.
The mouse died, and he recovered the pathogenic strain from
the mouse’s blood.
• Griffith called this phenomenon transformation, a phenomenon
now defined as a change in genotype and phenotype due to the
assimilation of foreign DNA by a cell. • For the next 14 years, scientists tried to identify the transforming
• Finally in 1944, Oswald Avery, Maclyn McCarty, and Colin
MacLeod announced that the transforming substance was DNA.
• Still, many biologists were skeptical.
Proteins were considered better candidates for the genetic
There was also a belief that the genes of bacteria could not be
similar in composition and function to those of more complex
• Further evidence that DNA was the genetic material was derived
from studies that tracked the infection of bacteria by viruses.
• Viruses consist of DNA (or sometimes RNA) enclosed by a
protective coat of protein.
To replicate, a virus infects a host cell and takes over the cell’s
Viruses that specifically attack bacteria are called
bacteriophages or just phages.
• In 1952, Alfred Hershey and Martha Chase showed that DNA was
the genetic material of the phage T2.
• The T2 phage, consisting almost entirely of DNA and protein,
attacks Escherichia coli (E. coli), a common intestinal bacteria of
• This phage can quickly turn an E. coli cell into a T2-producing
factory that releases phages when the cell ruptures.
• To determine the source of genetic material in the phage, Hershey
and Chase designed an experiment in which they could label
protein or DNA and then track which entered the E. coli cell during
They grew one batch of T2 phage in the presence of
radioactive sulfur, marking the proteins but not DNA.
They grew another batch in the presence of radioactive
phosphorus, marking the DNA but not proteins.
They allowed each batch to infect separate E. coli cultures.
Shortly after the onset of infection, they spun the cultured
that remained outside the bacteria.g loose any parts of the phage
The mixtures were spun in a centrifuge, which separated the
heavier bacterial cells in the pellet from lighter free phages and
parts of phage in the liquid supernatant.
They then tested the pellet and supernatant of the separate
treatments for the presence of radioactivity.
• Hershey and Chase found that when the bacteria had been
infected with T2 phages that contained radiolabeled proteins, most
of the radioactivity was in the supernatant that contained phage
particles, not in the pellet with the bacteria. • When they examined the bacterial cultures with T2 phage that had
the bacteria.DNA, most of the radioactivity was in the pellet with
• Hershey and Chase concluded that the injected DNA of the phage
produce new viral DNA and proteins to assemble into new viruses.
• The fact that cells double the amount of DNA in a cell prior to
provided some circumstantial evidence that DNA was the geneticell
material in eukaryotes.
• Sdiploid sets of chromosomes have twice as much DNA as thethat
haploid sets in gametes of the same organism.
• Ba survey of DNA composition in organisms.ries of rules based on
He already knew that DNA was a polymer of nucleotides
consisting of a nitrogenous base, deoxyribose, and a
The bases could be adenine (A), thymine (T), guanine (G), or
• Chargaff noted that the DNA composition varies from species to
• In any one species, the four bases are found in characteristic, but
not necessarily equal, ratios.
• Hthat are known as Chargaff’s rules.in the ratios of nucleotide bases
• In all organisms, the number of adenines was approximately equal
to the number of thymines (%T = %A).
• The number of guanines was approximately equal to the number
of cytosines (%G = %C).
• Human DNA is 30.9% adenine, 29.4% thymine, 19.9% guanine,
and 19.8% cytosine.
• The basis for these rules remained unexplained until the discovery
of the double helix.
Watson and Crick discovered the double helix by building
models to conform to X-ray data.
• By the beginnings of the 1950s, the race was on to move from the
structure of a single DNA strand to the three-dimensional structure
Among the scientists working on the problem were Linus
Pauling in California and Maurice Wilkins and Rosalind Franklin
• Maurice Wilkins and Rosalind Franklin used X-ray crystallography
to study the structure of DNA. In this technique, X-rays are diffracted as they passed through
aligned fibers of purified DNA.
The diffraction pattern can be used to deduce the three-
dimensional shape of molecules.
• James Watson learned from their research that DNA was helical in
nitrogenous bases.ced the width of the helix and the spacing of
Tstrands, contrary to a three-stranded model that Linus Pauling
had recently proposed.
• Wof DNA with two strands, the double helix.n to work on a model
• Using molecular models made of wire, they placed the sugar-
inside of the double helix.side and the nitrogenous bases on the
This arrangement put the relatively hydrophobic nitrogenous
bases in the molecule’s interior.
• Tof a rope ladder.e chains of each strand are like the side ropes
Pairs of nitrogenous bases, one from each strand, form rungs.
The ladder forms a twist every ten bases.
• The nitrogenous bases are paired in specific combinations:
adenine with thymine and guanine with cytosine.
• Pairing like nucleotides did not fit the uniform diameter indicated
by the X-ray data.
A purine-purine pair is too wide, and a pyrimidine-pyrimidine
pairing is too short.
Only a pyrimidine-purine pairing produces the 2-nm diameter
indicated by the X-ray data.
• In addition, Watson and Crick determined that chemical side
groups of the nitrogenous bases would form hydrogen bonds,
connecting the two strands.
Bhydrogen bonds only with thymine, and guanine would formwo
three hydrogen bonds only with cytosine.
This finding explained Chargaff’s rules.
• Tbases that form the “rungs” of DNA.ombinations of nitrogenous
• However, this does not restrict the sequence of nucleotides along
each DNA strand.
• The linear sequence of the four bases can be varied in countless
• Each gene has a unique order of nitrogenous bases.
• In April 1953, Watson and Crick published a succinct, one-page
paper in Nature reporting their double helix model of DNA. Concept 16.2 Many proteins work together in DNA replication
• The specific pairing of nitrogenous bases in DNA was the flash of
inspiration that led Watson and Crick to the correct double helix.
• The possible mechanism for the next step, the accurate replication
of DNA, was clear to Watson and Crick from their double helix
During DNA replication, base pairing enables existing DNA
strands to serve as templates for new complementary strands.
• In a second paper, Watson and Crick published their hypothesis
for how DNA replicates.
Eother, each can form a template when separated.y to the
Tcomplementary bases and therefore duplicate the pairs of
• When a cell copies a DNA molecule, each strand serves as a
strand.e for ordering nucleotides into a new complementary
Oaccording to the base-pairing rules.ong the template strand
The nucleotides are linked to form new strands.
• Watson and Crick’s model, semiconservative replication, predicts
that when a double helix replicates, each of the daughter
molecules will have one old strand and one newly made strand.
• Other competing models, the conservative model and the
dispersive model, were also proposed.
• Experiments in the late 1950s by Matthew Meselson and Franklin
Stahl supported the semiconservative model proposed by
Watson and Crick over the other two models.
In their experiments, they labeled the nucle15ides of the old
strands with a heavy isotope of nitrogen ( N), wh14e any new
nucleotides were indicated by a lighter isotope ( N).
Replicated strands could be separated by density in a
Each model—the semiconservative model, the conservative
model, and the dispersive model—made specific predictions
about the density of replic14ed DNA strands.
The first15ep14cation in the N medium produced a band of
hybrid ( N- N) DNA, eliminating the conservative model.
Aeliminating the dispersive model and supporting theDNA,
semiconservative model. A large team of enzymes and other proteins carries out DNA
• It takes E. coli 25 minutes to copy each of the 5 million base pairs
in its single chromosome and divide to form two identical daughter
• A human cell can copy its 6 billion base pairs and divide into
daughter cells in only a few hours.
• This process is remarkably accurate, with only one error per ten
• More than a dozen enzymes and other proteins participat