Transcript Genetica per Scienze Naturali aa 03

1. The laws of inheritance and the discovery of
chromosomes
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1866: Gregor Mendel publishes his findings on the laws of inheritance
based on experiments with pea plants. He develops three “principles”:
Dominance, Segregation, and Independent Assortment
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Mendel’s
1882: german biologist Walter Flemming, by staining cells
with dyes, discovers rod-shaped bodies he calls
"chromosomes."
laws of inheritance are rediscovered in 1900,
by the
German
botanist Carl
Correns
the Dutch
botanist
Hugo De
Vries
and the Austrian
agronomist
Erich von
Tschermak
Genetica per Scienze Naturali
a.a. 03-04 prof S. Presciuttini
2. Mendel's principles
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Dominance
 each inherited characteristic is determined by two
alternative hereditary factors, and one factor is
dominant over the other.
Segregation
 the sex cell of a plant or animal may contain one factor
(allele) for different traits but not both factors needed to
express the traits.
Independent assortment
 Different characteristics are inherited independently
from each other.
Genetica per Scienze Naturali
a.a. 03-04 prof S. Presciuttini
3. Where do genes reside?
In 1902, Walter Sutton (an American who at the time was a graduate
student) and Theodor Boveri (a German biologist) recognized
independently that the behavior of Mendel's particles during the
production of gametes in peas precisely parallels the behavior of
chromosomes at meiosis: genes are in pairs (so are chromosomes); the
alleles of a gene segregate equally into gametes (so do the members of a
pair of homologous chromosomes); different genes act independently
(so do different chromosome pairs). After recognizing this parallel
behavior, both investigators reached the same conclusion that the
parallel behavior of genes and chromosomes suggests that genes are
located on chromosomes.
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4. The word GENETICS is formulated
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1909: Danish botanist Wilhelm Johannsen
proposes the term "gene" (from the Greek
word "genos" which means "birth") to refer
to a Mendelian hereditary factor. Johannsen
also proposes two terms, genotype and
phenotype, to distinguish between one's
genetic make-up and one's outward
appearance.
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5. Genes are lined-up on chromosomes
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1915: Thomas Hunt Morgan, an American geneticist,
publishes The Mechanism of Mendelian Heredity, in
which he presents results from experiments with fruit
flies that prove genes are lined up along
chromosomes. He also describes the principle of
"linkage" — that alleles located relatively close to one
another on a chromosome tend to be inherited together.
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By studying the frequency with which traits are inherited together,
Morgan and co-workers create a "genetic map" of fruit fly
chromosomes showing the relative locations of the genes responsible
for dozens of traits, along with approximate distances between them
on the chromosome. This work establishes the basis for gene mapping
principles still used today.
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6. Genes may cause quantitative variation
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1918: R.A. Fisher shows that continuous
traits can be explained by Mendelian
segregation of genes: Mendel’s laws give
basis for statistical relationships between
parents and offspring.
His work reconciled the Darwinian view of
evolution with the findings of the geneticists,
posing the basis of the so-called “Modern
Synthesis”
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7. The first mutagenic agent
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In 1927 Herman Muller reported that X
rays could induce mutations in male fruit
flies. In his investigations Muller found
that the mutation rate among the male
fruit flies was linearly related to the
radiation dose. His results supplied the
first experimental evidence of a mutagen,
in this case, the X rays. Muller's work on
mutation induction opened the door to the
genetic technique of using mutations to
dissect biological processes, which is still
used extensively today
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8. An early hypothesis on the function of genes
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The first clues about the nature of primary gene function came
from studies of humans. Early in the twentieth century,
Archibald Garrod, a physician, made several observations about
alkaptonuria (a form of arthrytis) and proceeded to propose the
hypothesis that the information for producing specific enzymes
in humans is inherited. He observed that inherited diseases
reflect a patient's inability to make a particular enzyme, which
he referred to as "inborn errors of metabolism“.
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Garrod predicted that individuals affected with alkaptonuria would be deficient in
one of the enzymes in a degradative, biochemical pathway. He had suggested that
the specific enzyme was involved in the degradation of homogentisic acid, an
intermediate in the breakdown pathway of phenylalanine and tyrosine. He came
to this conclusion by feeding homogentisic acid to alkaptonuric patients and
noting that the chemical was excreted in the urine in quantitatively similar
amounts to what was administered.
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9. The Beadle and Tatum experiment
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Garrod's hypothesis was ahead of its time. Experiments that clarified
the actual function of genes came from research in the 1940s on
Neurospora by George Beadle and Edward Tatum, who later
received a Nobel Prize for their work.
Beadle and Tatum analyzed mutants of Neurospora crassa, a fungus
with a haploid genome. They first irradiated Neurospora cells to
produce mutations and then tested cultures from ascospores for
interesting mutant phenotypes. They detected numerous auxotrophs
strains (that cannot grow on a minimal medium unless the medium is
supplemented with one or more specific nutrients). In each case, the
mutation that generated the auxotrophic requirement was inherited
as a single-gene mutation: each gave a 1:1 ratio when crossed with a
wild type.
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10. The life cycle of a fungus
The fungus Neurospora spends most of its life cycle as a multicellular haploid
organism, in which the cells are joined end to end to form hyphae, or threads of cells.
The hyphae grow through the substrate and send up aerial branches that bud off
haploid cells known as conidia (asexual spores). Conidia can detach and disperse to
form new colonies
The fungus has alternate mating strains, here
called type A and type a. Mating can only
take place between different mating strains
and the result is a diploid cell in a long sac
(ascus). The diploid cell undergoes meiosis
producing four haploid cells.
In the ascus, the results of segregation during
metaphase 1 are kept in order. These haploid
cells undergo one cycle of mitosis in the
ascus leading to 8 spores (called ascospores)
in order in the ascus.
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11. Auxotroph mutants
One set of mutant strains
required arginine to grow on a
minimal medium. These
strains provided the focus for
much of Beadle and Tatum's
further work.
They found that the mutations
mapped into three different
locations on separate
chromosomes, even though
the same supplement
(arginine) satisfied the growth
requirement for each mutant.
Genetica per Scienze Naturali
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12. Inferring a metabolic pathway
Beadle and Tatum discovered that the auxotrophs
for each of the three loci differed in their response
to the chemical compounds ornithine and
citrulline, which are related to arginine.
One mutant strain grew when supplied with
ornithine, citrulline, or arginine in addition to the minimal
medium, another grew on either arginine or citrulline but not on
ornithine, and the third grew only when arginine was supplied.
On the basis of the properties of the arg mutants, Beadle and
Tatum and their colleagues proposed a biochemical model for
such conversions in Neurospora
Genetica per Scienze Naturali
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13. The one-gene one-enzyme hypothesis
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Beadle and Tatum concluded that a mutation at a particular gene affects the
functioning of a single enzyme. The defective enzyme, then, creates a block in
some biosynthetic pathway.
This entire model was inferred from the properties of the mutant classes detected
through genetic analysis. Only later were the existence of the biosynthetic
pathway and the presence of defective enzymes demonstrated through
independent biochemical evidence.
This model, which has become known as the one-gene one-enzyme hypothesis,
was the source of the first exciting insight into the functions of genes: genes
somehow were responsible for the function of enzymes, and each gene apparently
controlled one specific enzyme.
Other researchers obtained similar results for other biosynthetic pathways, and the
hypothesis soon achieved general acceptance. The one-gene one-enzyme
hypothesis became one of the great unifying concepts in biology, because it
provided a bridge that brought together the concepts and research techniques of
genetics and biochemistry.
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14. Which macromolecule carry the genes?
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Chromosomes are composed of both DNA and proteins;
early observations pointed to DNA as the molecule carring
the genetic information, but many scientists were very
reluctant to accept this idea. DNA was thought to be a
simple and repetitive chemical. How could all the
information about an organism's features be stored in such
a simple molecule? How could such information be passed
on from one generation to the next? Clearly, the genetic
material must have both the ability to encode specific
information and the capacity to duplicate that information
precisely. What kind of structure could allow such
complex functions in so simple a molecule?
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15. An experiment with bacteriophages
Resolution was provided in 1952 by
Alfred Hershey and Martha Chase
with the use of the phage T2 (a virus
specific to bacteria). The phage is
relatively simple in molecular
constitution. Most of its structure is
protein, with DNA contained inside
the protein sheath of its "head.“
The phage attaches to a bacterium's cell wall via
its "tails" (shown in green) and injects its genes
into the bacterium through its syringe-like blue
column. It commandeers the bacterium's cellular
machinery to make new phages. The cell
eventually becomes so crowded, it bursts,
releasing the new phages that head off to invade
other cells.
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16. 32P and 35S
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Phosphorus is not found in proteins but is an integral part of DNA; conversely,
sulfur is present in proteins but never in DNA.
Hershey and Chase incorporated the radioisotope of phosphorus (32P) into phage
DNA and that of sulfur (35S) into the proteins of a separate phage culture.
They then used each phage culture independently to infect E. coli with many virus
particles per cell. After sufficient time for injection to take place, they used
centrifugation to separate the bacterial cells from the phage ghosts and then
measured the radioactivity in the two fractions.
When the 32P-labeled phages were used, most of the radioactivity ended up inside
the bacterial cells, indicating that the phage DNA entered the cells. 32P can also
be recovered from phage progeny.
When the 35S-labeled phages were used, most of the radioactive material ended up
in the phage ghosts, indicating that the phage protein never entered the bacterial
cell (Figure 8-3).
The conclusion is inescapable: DNA is the hereditary material; the phage proteins
are mere structural packaging that is discarded after delivering the viral DNA to
the bacterial cell.
Genetica per Scienze Naturali
a.a. 03-04 prof S. Presciuttini
17. DNA is the genetic material
The Hershey-Chase
experiment, which
demonstrated that
the genetic material
of phage is DNA,
not protein.
Genetica per Scienze Naturali
a.a. 03-04 prof S. Presciuttini