Download 1 Molecular Genetics

A A. Abugabal
GEN 301

Acquire the students with

good basic grounding in the molecular structure,
organization and function of genetic material
 To distiguish between different types
of
molecular markers
 To critically appraise the different methods used
in molecular mapping
 To study the application of genetic analysis in
different organisms
•Assessment Details:
Methods of Assessment
Weighting %
Project
7%
Quizzes
3%
Assignments
5%
Mid-Term
20%
Lab Work
25%
Final Exam:
40%

The history of genetics is quite extensive.

It has taken the work of many brilliant
scientists to finally conceive the structure of the
DNA molecule or to even conceive it as the
hereditary material life.

In this opening genetics section it is important to
understand scientists' achievements.

Appreciate and understand their method, do
not get caught up in history and dates.
Gregor Mendel: mid 1800’s

1865 Gregor Mendel

By studying pea plants,

discover the basic rules of heredity of garden
pea.
 Characteristics
are inherited in discrete units
(later called genes)
 An individual organism has two alternative
heredity units for a given trait (dominant
trait vs. recessive trait)

1869 Johann Friedrich
Miescher
discovered
DNA
and
named
it
nuclein.
1881
Edward
Zacharias
showed chromosomes are
composed of nuclein.
Johann Miescher

1899 Richard Altmann
renamed
nuclein
to
nucleic acid.

By
1900,
chemical
structures of all 20 amino
acids had been identified

1902 - Emil Hermann Fischer
wins Nobel prize: showed
amino acids are linked and
form proteins
Emil
Fischer

Thomas Hunt Morgan
 Worked at Columbia University; later
at CalTech
 Studied fruit fly eye color, determining
that trait was sex-linked
 Won the Nobel Prize in 1933 for his
work on chromosomes and genetics

1911 – Thomas Hunt Morgan
discovers genes on chromosomes
are the discrete units of heredity
Thomas
Morgan
early 1900’s
Studied fruit fly eye
color, determining that
trait was sex-linked
1911 – Thomas
Hunt
Morgan
discovers genes on
chromosomes are
the discrete units
of heredity
Won the Nobel Prize in 1933 for
his work on chromosomes and
genetics

By this point, it was known that
genetic material was located on
a chromosome

This genetic material was
discrete units called genes
in
Components Involve in Molecular Biology
DNA
By this stage , It was
NOT known whether
the gene was simply
a
protein,
or
whether
it
was
composed of DNA
RNA
Protein
Since the late 1950s and early 1960s,
molecular biologists have learned to
 Characterize, isolate, and manipulate the
molecular components of cells and organisms,
which are:
1. DNA,
the storage of genetic
information
2. RNA
3. Proteins, the major structural and
enzymatic type of molecule in cells.


1930’s
 Various experiments identify chromosomes as
the source of genetic information
 Chromosomes are composed of mainly proteins
and deoxyribonucleic acid (DNA)
 The DNA molecule was considered too simple to
be important so
proteins were
thought to carry the genetic
information
The Molecular Basis of Inheritance
Evidence that DNA is
a genetic material
Came from
Fred Griffith (1928) – Experiments with pneumonia and bacterial
transformation determined that there is a molecule that controls
inheritance.
Oswald T. Avery (1944) - Transformation experiment determined
that DNA was the genetic material responsible for Griffith’s results
(not RNA).
Erwin Chargaff (1947) – noted that the the amount of A=T and
G=C and an overall regularity in the amounts of A,T,C and G within
species.
Hershey-Chase Experiments (1952) – discovered that DNA from
viruses can program bacteria to make new viruses.
Late 1920’s Frederick
Griffith
from
Britain
worked with bacteria
“Streptococcus pneumoniae”
 Defined
the
term,

“TRANSFORMATION”

Their conclusion was based on experimental evidence that
only DNA worked in transforming harmless
bacteria into pathogenic bacteria
Hershey and Chase concluded that the injected DNA
of the phage provides the genetic information that
makes the infected cells produce new viral DNA and
proteins, which assemble into new viruses.
Conclusions about these early
experiments:
Griffith 1928 & Avery 1944:
DNA (not RNA) is transforming agent.
Hershey-Chase 1953:
DNA (not protein) is the genetic material.
- RNA (not protein) is genetic material of some viruses,
- but no known prokaryotes or eukaryotes use RNA as
their genetic material.
Alfred Hershey
Nobel Prize in Physiology or Medicine
1969
22

Won Nobel prize in chemistry in
1954 for work in chemical bonding;

Nobel peace prize in 1962 for his
campaign against above-ground
nuclear testing

He also worked on the structure of
DNA, but came up with a TRIPLE
HELIX
 He thought DNA was 3
strands with the phosphates on
the inside
1950 – Edwin Chargaff find
Cytosine complements Guanine
and Adenine complements Thymine
Edwin Chargaff
X-ray diffraction studies of Rosalind
Franklin & Maurice H. F. Wilkins to study What about?
the structure of DNA.
Rosalind Franklin
 The diffraction pattern can be used to
deduce the three-dimensional shape of
molecules.


Their results using X-ray crystallography gave Watson and Crick the necessary
information they needed to come up with the double helix structure
 Width of the helix
 Spacing of the nitrogenous bases
 DNA molecule was made up of two strands, forming a double helix
1953 proposed the Double Helix Model
based on two sources of information
Structure of DNA
1. Base composition studies of Erwin
Chargaff
•
•
indicated double-stranded DNA consists of
~50% purines (A,G) and ~50% pyrimidines (T, C)
•
•
amount of A = amount of T and
amount of G = amount of C
(Chargraff’s rules)
•
%GC content varies from organism to organism
Examples:
%A
Homo sapiens
31.0
Zea mays
Drosophila
Aythya americana 25.8
%T
31.5
25.6
27.3
25.8
%G
19.1
25.3
27.6
24.2
%C
18.4
24.5
22.5
24.2
%GC
37.5
24.6
22.5
48.4
49.1
45.0
28
Two sources of information
Structure of DNA
James D. Watson/Francis H. Crick 1953 proposed the Double Helix
Model based on two sources of information:
2. X-ray diffraction studies by Rosalind Franklin &
Maurice Wilkins
Conclusion-DNA is a helical structure with
distinctive regularities, 0.34 nm & 3.4 nm.
29
Watson, J.D. and F.H. Crick, “Molecular
Structure of Nucleic Acids.
Francis H.Crick
James D.Watson
1962: Nobel Prize in Physiology and Medicine
Conclusion-DNA is a helical structure with
distinctive regularities, 0.34 nm & 3.4 nm.

1941 – George Beadle and Edward
Tatum identify that
genes make
proteins

1950s – Mahlon Bush Hoagland first to
isolate tRNA


George
Beadle
Edward
Tatum
Mahlon
Hoagland
George
Emil
Palade
1952 – Alfred Hershey and Martha Chase
make genes from DNA
1956 George Emil Palade showed the
site of enzymes manufacturing
in the cytoplasm is made on RNA
organelles called ribosomes.

1970 Howard Temin and David
Baltimore independently isolate the
first restriction enzyme
•
This means that: DNA can be cut
into reproducible pieces at specific
site by restriction enzymes called
endonuclease
•
The pieces can be linked to bacterial
vectors and introduced into bacterial
hosts.This is called (gene cloning or
recombinant DNA technology)

1977 Phillip Sharp
and Richard Roberts
demonstrated
that
pre-mRNA
is
processed
by
the
excision of introns
and
exons
are
spliced together.
Phillip Sharp
Richard Roberts

1986 Leroy Hood: Developed
automated sequencing
mechanism

1986 Human Genome
Initiative announced
1995 Moderate-resolution
maps of chromosomes 3, 11,
12, and 22 were published
 These maps provide the
locations of “markers” on
each chromosome to make
locating genes easier

Leroy Hood

1995 John Craig Venter: First
bacterial genomes sequenced

1995 Automated fluorescent
sequencing instruments and
robotic operations

1996 First eukaryotic genomeyeast-sequenced
John Craig Venter
 Molecular Biology 1997-1999
 1999 First human chromosome
(number 22) sequenced
 Molecular Biology 2000-2001
• 2001 International Human
Genome Sequencing published
the first draft of the sequence
of the human human genome

April 2003 Human Genome
Project Completed

Mouse genome is sequenced.

April 2004 Rat genome
sequenced.

Next-generation sequencing –
genomes being sequenced by
the dozen

Molecular genetics is the field of biology and genetics that
studies the structure and function of genes at a molecular level.

Molecular genetics employs the methods of genetics and
molecular biology to elucidate molecular function and
interactions among genes. It is so called to differentiate it from
other sub fields of genetics such as ecological genetics and
population genetics.

Molecular genetics helps in understanding developmental
biology, genetic mutations that can cause certain types of
diseases.

Through utilizing the methods of genetics and molecular
biology, molecular genetics discovers the reasons why traits are
carried on and how and why some may mutate.