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The Academic Support Center @ Daytona State College (Science 108, of 31)

R E V I E W

GENETICSTHE SCIENTISTS


Harvey

• William Harvey (1578–1657) wrote a treatise on reproduction and

development patterned after Aristotle’s work. He is credited with the

earliest statement of the theory of epigenesis, which posits that an

organism is derived from substances present in the egg that

differentiate into adult structures during embryonic development.

Epigenesis holds that structures such as body organs are not initially

present in the early embryo but instead are formed de novo (anew).


Schleiden and Schwann

• Around 1830, Matthias Schleiden, and Theodor Schwann proposed

the cell theory, stating that all organisms are composed of basic units

called cells, which are derived from similar preexisting structures.

• The idea of spontaneous generation, the creation of living organisms

from nonliving components, was disproved by Louis Pasteur later in

the century, and living organisms were considered to be derived from

preexisting organisms and to consist of cells.


Darwin


Mendel

• Gregor Mendel• Proposed the existence of particulate unit factors (genes) are

passed from generation to generation

• Proposed four postulates of inheritance

• Unit factors (alleles of genes) exist in pairs (in diploid)

• If an organism has two different alleles (heterozygous) then one is dominant and the other is recessive. One expresses phenotype in heterozygote, and the other is hidden in heterozygote

• The paired unit factors segregate independently during gamete formation (meiosis).

• All possible combinations of gametes will form with equal frequency

• Proposed that traits assort independently during gamete formation.

• Used true breeding strains of peas with seven characteristics, each characteristic had two contrasting traits.


Mendel


Hardy and Weinburg• The relationship between the relative

proportions of alleles in the gene pool

and the frequencies of different

genotypes in a population was

described in the early 1900s in a

simple mathematical model

developed independently by the

British mathematician Godfrey H.

Hardy and the German physician

Wilhelm Weinberg.


Hardy and Weinburg

• Given 36% of the population is blue eyed (recessive

phenotype)… what is p and q? p2, 2pq:

• Given that 36% is recessive then q2 = .36, therefore q = .6

• p + q = 1, therefore p = .4

• p2 = .16 and 2pq = .48

• To double check p2 + 2pq + q2 = 1

• .16 + .48 + .36 = 1

• Therefore dominant phenotype = 16%

Heterozygotes = 48%


Hardy and Weinburg


Luria and Delbruck

• In 1943, Salvador Luria and Max

Delbruck presented the first

direct evidence that mutations

do not occur as part of an

adaptive mechanism, but

instead take place

spontaneously and randomly.


• In 1952, Norton Zinder and Joshua

Lederberg were investigating

possible recombination in the

bacterium Salmonella typhimurium.

What they discovered was a process

of bacterial recombination

mediated by bacteriophages and

now called transduction.

Lederberg and Zinder


Griffith

• Frederick Griffith in 1927 showed that avirulent strains of Diplococcus pneumoniae could be transformed to virulence.

• He speculated that the transforming principle could be part of the polysaccharide capsule or some compound required for capsule synthesis.

• Proved there was a transforming principle.


Avery, McLeod and McCarty

• The 1944 publication by

Oswald Avery, Colin

MacLeod, and Maclyn

McCarty concerning the

chemical nature of a

“transforming principle” in

bacteria was the initial

event leading to the

acceptance of DNA as the

genetic material.


Hershey and Chase

• In 1952, Alfred Hershey and Martha

Chase using Escherichia coli and an

infecting virus (bacteriophage T2),

demonstrated DNA, and not protein,

is the genetic material.


Chargaff

• The proportions change from species to species.

• Between 1949 and 1953, Erwin Chargaff and his colleagues used

chromatographic methods to separate the four bases in DNA samples

from various organisms. Quantitative methods were then used to

determine the amounts of the four bases from each source.


Chargaff• Between 1949 and 1953, Erwin Chargaff and his colleagues used

chromatographic methods to separate the four bases in DNA samples

from various organisms. Quantitative methods were then used to

determine the amounts of the four bases from each source.


Chargaff

Examples

• If A = 23% what is T, G and C?

• A = T; therefore T = 23%

• A + T + G + C = 100%; therefore 23 + 23 + G + C = 100%

• G + C = 54%

• G = C; therefore C = 27% and G = 27%


Watson and Crick• In 1953, James Watson and Francis Crick proposed that the structure of

DNA is in the form of a double helix. The data available to Watson and

Crick, crucial to the development of their proposal, came primarily from

two sources: (1) base composition analysis of hydrolyzed samples of DNA

and (2) X-ray diffraction studies of DNA. Watson and Crick’s analytical

success can be attributed to their focus on building a model that

conformed to the existing data.


Meselson and StahlMatthew Meselson and Franklin Stahl

• The Meselson-Stahl experiment demonstrated that:

• DNA replication is semiconservative

• Each new DNA molecule consists of one old strand and one

newly synthesized strand.


Meselson and Stahl


Taylor, Woods, and Hughes


Ames• In 1974, Bruce Ames developed a simple test for

evaluating the potential of chemicals to cause

cancer. The Ames test is based on the principle

that both cancer and mutations result from

damage to DNA, and the results of experiments

have demonstrated that 90% of known

carcinogens are also mutagens. Ames proposed

that mutagenesis in bacteria could serve as an

indicator of carcinogenesis in humans.

• A bacterial assay developed by Bruce Ames to

detect mutagenic compounds; it assesses

reversion to histidine independence in the

bacterium Salmonella typhimurium.


Ames

• Ames test• The Ames test uses a number of different

strains of Salmonella typhimurium selected

for their ability to reveal the presence of

specific types of mutations

• The Ames test is used extensively during

the development of industrial and

pharmaceutical chemical compounds

• Many known carcinogens have been

shown by the Ames test to be strong

mutagens.

• More than 60 compounds found in

cigarette smoke test positive in the

Ames test and cause cancer in animals.

• Note this is a first step, not proof of

carcinogen.


Nirenberg and Matthaei• Nirenberg and Matthaei

• Cracked the genetic code by using nucleic acid homopolymers to translate specific amino acids.

• Added RNA homopolymers to the in vitro translation system to decipher which amino acids were encoded by the first few codons based on which amino acids were incorporated into the polypeptide.

• In 1961, Marshall Nirenberg and J. Heinrich Matthaei became the first to characterize specific coding sequences, laying a cornerstone for the complete analysis of the genetic code. Their success, as well as that of others who made important contributions in deciphering the code, was dependent on the use of two experimental tools, an in vitro (cell-free in a test tube) protein-synthesizing system and the enzyme polynucleotide phosphorylase, which allowed the production of synthetic mRNAs. These mRNAs served as templates for polypeptide synthesis in the cell-free system.

• RNA homopolymers• RNA nucleotides with only one type of ribonucleoside

• RNA heteropolymers• RNA nucleotides with two or more different ribonucleosides


• Nirenberg and Leder• Developed the triplet binding assay to determine other specific codon

assignments.• In 1964, Nirenberg and Philip Leder developed the triplet binding assay,

leading to specific assignments of triplet codons. • Triplet binding essay

• In this technique ribosomes bind to a single codon of three nucleotides and the complementary amino acid charged tRNA will be able to bind.

• This technique took advantage of the observation that ribosomes, when presented in vitro with an RNA sequence as short as three ribonucleotides, will bind to it and form a complex similar to what is found in vivo. The triplet RNA sequence acts like a codon in mRNA, attracting a tRNA molecule containing a complementary sequence. Such a triplet sequence in tRNA, that is, complementary to a codon of mRNA, is known as an anticodon.

Nirenberg and Leder


Crick• Wobble hypothesis

• Predicts that the initial two ribonucleotides of triplet codes are often more critical than the third. The third position of the codon-anticodon interaction would be less spatially constrained and need not adhere as strictly to the established base-pairing rules at the third position of the codon.

• An idea proposed by Francis Crick, stating that the third base in an anticodon can align in several ways to allow it to recognize more than one base in the codons of mRNA.


Holley• In 1965, Robert Holley and his colleagues

reported the complete sequence of tRNAAla

isolated from yeast. Of great interest was their finding that a number of nucleotides are unique to tRNA, each containing a so-called modified base.

• These modified structures are created after transcription of tRNA, illustrating the more general concept of posttranscriptional modification.

• Holley’s sequence analysis led him to propose the two-dimensional cloverleaf model of tRNA. It had been known that tRNA has a characteristic secondary structure created by base pairing. Holley discovered that he could arrange the linear sequence in such a way that several stretches of base pairing would result.

His arrangement, with its series of paired stems and unpaired loops, resembled the shape of a cloverleaf.


Beadle and Tatum

• Beadle and Tatum

• Beadle and Tatum (1940’s)

showed that nutritional

mutations in the bread mold

Neurospora caused the loss of

an enzymatic activity that

catalyzes an essential reaction in

wild-type organisms

• One gene one enzyme

hypothesis.


Jacob and Monod• Jacob and Monod

• In 1961, François Jacob and Jacques Monod described the “operon model” for the genetic control of lactose metabolism in E. coli. This work and subsequent research on the genetics of lactose metabolism established the operon as the basic unit of transcriptional control in bacteria. Despite the fact that, at the time, no methods were available for determining nucleotide sequences, Jacob and Monod deduced the structure of the operon genetically by analyzing the interactions of mutations that interfered with the normal regulation of lactose metabolism.


Prepared and Compiled from various sources by D. Leonard (Learning Specialist)The Academic Support Center @ Daytona State Collegehttp://www.daytonastate.edu/asc/ascsciencehandouts.html

Questions

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