The document provides an extensive overview of genetics, including the history and significance of DNA, chromosomes, and genes in heredity and variation among organisms. It highlights key discoveries in molecular biology, including important experiments that established DNA as the hereditary material, and outlines the structure of DNA as a double helix. Additionally, it details milestones in genetics research, from Mendel's foundational work to modern advancements in DNA sequencing and genetic engineering.

1. DNA
The Code of Life
The Molecular Basis of Inheritance

2. Genetics
• The branch of biology that deals with the study of heredity
• Genetics is derived from the Greek genno = give birth
• Genetics is the science of genes, heredity and the variation of
organisms
• The word genetics was first applied to describe “the study of
inheritance and the science of variation” by English scientist
William Bateson in a letter to Adam Sedgewick, in 1905
• Later Bateson used this word in 1906 in 3rd
Conference on
Hybridization and Plant Breeding

3. Chromosome
• Structure composed of a very long DNA molecule & associated
proteins that carries part or all of the hereditary information of an
organism
• Especially evident in plant & animals cells undergoing mitosis or
meiosis, where each chromosome become condensed into a
compact rod-like structure visible under the light microscope
• A chromosome (in Greek chroma = color and soma = body) is,
minimally, a very long, continuous piece of DNA, which contains
many genes, regulatory elements and other intervening nucleotide
sequences
• By the mid-to-late 1800s, may studies suggested that cell nucleus
possessed unique properties that might play a key role in heredity
• Chromosomes were first observed by Nageli in 1842

4. Chromosome
• In early 1869, Friedrich Miescher reported that the nuclei of human
WBCs contain a unique chemical component rich in phosphorus
called “nuclein”
• Their detailed behavior was described by Flemming in 1882
• In 1910, Morgan proved that chromosomes are the carriers of genes
• Chromatin: complex of DNA, and histones proteins found in the
nucleus of a eukaryotic cell.
• Chromatid: one copy of a chromosome formed by DNA replication
that is still joined at the centromere to the other copy. The two
identical chromatids are called sister chromatids

5. Chromatin and associated proteins
• DNA winds around histone
proteins (nucleosomes)
• Other proteins (non
histone) wind DNA into
more tightly packed form,
the chromosome
• Unwinding portions of the
chromosome is important
for mitosis, replication and
making RNA

6. Gene
• Fundamental unit of heredity
• Inherited determinant of a phenotype
• Segment of DNA sequence corresponding to a single protein (or to
a single catalytic or structural RNA)
• It is the information containing element that determine the
characteristics of a species as a whole and of the individuals with in
it
• Sequence of DNA that instructs a cell to produce a particular
protein
• Locus (pl: loci): position occupied by a gene on a chromosome

7. Gene

8. Terminology
• Genome: an organism’s complete genetic material
• The genome is an organism’s complete set of DNA
– A bacteria contains about 600,000 DNA base pairs
– Human genomes have some 3 billion bp on 23 pairs of
chromosomes
• Genotype: The genetic makeup of an organism
• Phenotype: the physicaly expressed traits of an organism
• Proteins:
– Make up the cellular structure or are enzymes
– large, complex molecules made up of smaller subunits called
amino acids

9. Jobs of a Genetic Material
• Substance responsible for passage of traits from parents to offspring
• “A genetic material must carry out two jobs:
– Duplicate/Replicate itself
– Control the development of the rest of the cell in a specific way”
• Interesting question: Which of the following can/cannot be regarded
as genetic material
– Plant DNA
– Human mRNA
– Bacterial plasmids
– Plastid/mitochondrial DNA
– RNA viruses

10. Qualities of Genetic Material
• It must be able to replicate accurately in order to be in each cell of
a growing organism
• It must be able to expression of traits
• It must be able to change in controlled way, in order to ensure
survival of a species in a changing environment for evolution or to
allow evolution
• It must be stable enough to store information for a long period of
time

11. DNA or Protein – What contains Hereditary
Information?
• Although we now accept the idea that DNA is responsible for our
biological structure
• However, in the early 1800s it was unthinkable for the leading
scientists and philosophers that a chemical molecule could hold
enough information to build a human
• They believed that plants and animals had been specifically
designed by a creator

12. DNA or Protein – What contains Hereditary
Information?
• Many scientists favored proteins until the mid-1940’s.
• DNA is simple chemically (4 nucleotides known); how could it then
hold complex genetic information?
• Proteins are much more complicated chemically (20 amino acids)
and more abundant; perhaps they hold genetic information
• Quantitative analysis of cells reveals that:
– DNA Protein
– 40% 60%
– 4 nucleotides 20 amino acids
– Less variable More variable

13. “The Origin of Species”
• Charles Darwin is famous for challenging this view
• In 1859 he published 'The Origin of Species‘ expressing that living
things might appear to be designed, but were actually the result of
natural selection
• Darwin showed that living creatures evolve over several
generations through a series of small changes

14. Mendel’s work
• In the 1860s Darwin's ideas were supported when genetics was
discovered by Gregor Mendel
• He found that genes determine the characteristics a living things
• The genes are passed on to later generations, with a child taking
genes from both its parents
• The great mystery was where and how this information (genes) is
stored?

15. Hereditary factors vs. chromosome
• Proof that chromosomes were the Mendel’s hereditary factors came
in 1905, when first time physical trait was shown to be the result of
the presence or absence of specific chromosome
– Variety of chromosome types differing in size & shape, present
in nucleus of each cell & usually 2 copies of each type.
– All cells of an organism & all organisms of same species have
same # of chromosomes.
– # of chromosomes doubled prior to cell division in which cell
splits to form two identical cells.
– Sex or germ cell have half # of chromosome called haploid cell.
– Fertilization of germ cells produce diploid cell called zygote
have same # of chromosome as somatic cells.

16. Is DNA the genetic material in eukaryotes?
• Indirect evidence - DNA and RNA absorb UV Light
• Action spectrum of UV-induced mutations in bacteria correlates with
absorption spectrum of UV light for nucleic acids, not protein.
• Can be use to quantify amounts of nucleic acid and protein.
• Direct evidence?

17. Evidence for DNA as Hereditary Molecule
• Transformation studies
– Griffith (1928)
– Avery, MacLeod and McCarty (1944)
• Hershey-Chase experiment (1952)
• Molecular Studies

18. Transforming principle
• Frederick Griffith, 1928
– Pneumonia (Diplococcus pneumoniae) infects mice
– Mice develop pneumonia and die
• Two types of bacteria:
– R bacteria - rough coat - no pneumonia
– S bacteria - smooth coat- pneumonia
• Assumption: Coat type is associated with virulence

19. Bacterial
colonies
Rough
nonvirulent
(strain R)
Injection
Results
Mouse healthy
Smooth
virulent
(strain S)
Mouse dies
Heat-killed
smooth
virulent
(strain S)
Live strain S bacteria
in blood sample
from dead mouse
Mouse dies
Mouse healthy
+
Rough
nonvirulent
(strain R)
Heat-killed
smooth
virulent
(strain S)
Griffith’s experiment for “transforming
principle”

20. What is the “transforming principle”?
• Oswald Avery, Colin MacLeod and Maclyn McCarty, 1944
• Heat-killed S bacteria “transformed” the R bacteria to a form that
causes pneumonia
• Conclusion: DNA is the transforming principle allowing R bacteria
to make a smooth coat and allow infection

21. Avery, MacLeod, and McCarty Expt:
DNA is the “Transforming Principle”

22. Hershey-Chase Experiment
• Study of infection of E. coli by T2 phage
• Radioactively labeled DNA and protein:
– 32
P atom is in phosphate molecules in DNA and RNA, only at
low levels in protein (phosphorylated proteins)
– 35
S atom is in sulfur-containing amino acids (cysteine and
methionine); not in DNA or RNA

23. Non-radioactive medium
+ bacteria
Phage Made Radioactive

24. 32
P Phage 35
S Phage
Label (protein) is outside
Label
(DNA)
is inside
Phage Infect Cells

25. Why is DNA a good material for storing
genetic information?
• A linear sequence of bases has a high storage capacity
• a molecule of n bases has 4n
combinations
• A molecule just 10 nucleotides long – 410
or 1,048,576
combinations
• Humans – 3.2 x 109
nucleotides long – 3 billion base pairs

26. The discovery of DNA structure
• The DNA molecule was discovered in 1951 by Francis Crick, James
Watson and Maurice Wilkins using X-ray Diffraction
• In 1953, Francis Crick and James Watson, two scientists working at
the Cavendish Laboratory in Cambridge, discovered the structure of
the DNA a double helix, or inter-locking pair of spirals, joined by
pairs of molecules.
• DNA was built from similar units – the bases adenine (A) thymine
(T) guanine (G) and cytosine (C)

27. Watson and Crick with their DNA
model
Crick, Watson and Wilkins won the Nobel Prize for medicine in 1962

28. Watson & Crick model
• They deduced from X-ray data that:
– Double helix
– Uniform width of 2 nm
– Bases stacked 0.34 nm apart
• Implies Chargoff’s “rules”
– Adenine pairs with thymine
– Cytosine pairs with guanine

29. Important discoveries in
the filed of Molecular
Biology

30. 1968-77
• 1968 - Hamilton Smith: discovered HindII in Haemophilus
influenzae
• 1971- Daniel Nathans: used HindII to make first restriction map of
SV40
• 1972 - Paul Berg: Produced first recombinant DNA using EcoRI
• 1973 - Boyer, Cohen & Chang: Transformed E. coli with
recombinant plasmid
• 1977 - Genentech, Inc.: Considered the advent of the Age of
Biotechnology - First human protein (somatostatin) produced from a
transgenic bacterium
• 1977 - Walter Gilbert and Allan Maxam devised a method for
sequencing DNA.

31. 1978-84
• 1978 - David Botstein discovered RFLP analysis
• 1980 - Kary Mullis developed PCR. Sold patent for $300M in 1991
• 1981 - First transgenic mice produced
• 1982 - The USFDA approved sale of genetically engineered
human insulin
• 1983 - An automated DNA sequencer was developed
• 1983 - A screening test for Huntington’s disease was developed
using restriction fragment length markers.
• 1984 - Alec Jeffreys introduced technique for DNA fingerprinting to
identify individuals

32. 1985-94
• 1985 - Genetically engineered plants resistant to insects, viruses,
and bacteria were field tested for the first time
• 1985 - The NIH approved guidelines for performing experiments in
gene therapy on humans
• 1987 - Invention of YACs (yeast artificial chromosomes) as
expression vectors for large proteins
• 1989 - National Center for Human Genome Research was
created to map and sequence all human DNA by 2005.
• 1990 - First gene therapy attempted on a four-year-old girl with an
inherited immune deficiency disorder
• 1994 - The first genetically engineered tomato gains FDA
approval
• 1994- The first linkage map of the human genome appears

33. 1995-99
• 1995 - The first full gene sequence of a living organism is
completed for Hemophilus influenzae.
• 1996 - The yeast genome, containing approximately 6,000 genes
and fourteen million nucleotides, is sequenced.
• 1997 - Dolly cloned from the cell of an adult ewe
• 1997 - DNA microarray technology developed
• 1997 - The genome of the bacterium E. coli, was completely
sequenced, revealing about 4,600 genes and 4.5 million
nucleotides.
• 1999 - Jesse Gelsinger, an eighteen year-old with a genetic
disorder affecting liver metabolism, dies from an immune reaction to
a gene therapy treatment.

34. 1999-2000
• 1999 - The first complete sequence of a human chromosome
(number 22) was completed by the public genome project and is
published.
• 2000 - The genome of the fruitfly (Drosophila melanogaster)
was sequenced, identifying approximately 13,000 genes among
170 million nucleotides.
• 2000 - First plant genome sequenced (Arabidopsis thaliana).
The Arabidopsis genome consists of about 100 million nucleotides,
and approximately 20,000 genes.
• 2000 - "Golden rice," a genetically engineered strain of rice
manufactures its own vitamin A.

35. 2001-04
• 2001 - International Human Genome Sequencing: First draft of
the sequence of the human genome published
• 2003 - Human Genome Project Completed. Mouse genome is
sequenced.
• 2004 - Rat genome sequenced.

36. 2005-10
• 2005: Dog Genomes Sequenced
• 2006 - The Protein Data Bank containing nearly 40,000 atomic-
resolution structures of proteins was been established
• 2006: Second Non-human Primate (Rhesus) Genome is
Sequenced
• 2009 - Nobel Prize in Chemistry was awarded to Ada Yonath,
Venkatraman Ramakrishnan, and Thomas Steitz for their structural
work on the ribosome.
• 2010 – Arabidopsis Project Completed: understanding the
function of all genes within their cellular, organismal and
evolutionary context of Arabidopsis thaliana

37. Extraction
• Each human cell has enough DNA to code for all the traits in the
human body. If the DNA in one cell was stretched out, how long
would it be? Do the math!
• There are 6 X 109
base pairs/cell
Each base pair is 0.34 X 10-9
meters long
• Answer: 2 meters
• A human body has approximately 75 trillion cells. If the distance to
the sun is 150 X 109
meters, how many round trips could your DNA
make?
• Answer: 500 trips