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Introduction to Genetics
Dr. Sibel YILMAZ
Lesson I & II
Subjects: History of Genetics, Genes,
Alleles, Mutations, Variations and
Units
What is Genetics?
• Ancient Greek word Genesis: origin, formation,
creation…
• Genetics is a discipline that study about genes,
variations and heredity in organisms.
• Genetics is a multidisciplinary science.
• But generally it is considered as a field of biology.
• Genetics works together with biology, chemistry,
physics, computer technology ect.
• It is considered one of the most important science
for the future.
History of Genetics
• Life arose more than 4 billion years ago
• And human first appeared 200 thousand
years ago.
• Human always wonder about the origin of
life and inheritance of characters.
• Many theories produced.
• The most important results were obtained
from Mendel studies.
• His studies have been accepted as the
beginning of modern genetics.
Before Mendel
• Theories were propounded by
ancient philosophers, are generally
nonsensical.
1. Spontaneous
formation
(Abiogenesis)
• According to this theory
nonliving things can
produce living things at
the proper conditions.
• Invalidity of this theory
can be proved by many
experiments.
• Following times scientics have
different perspectives.
• The most widely accepted
theory is Preformationism
theory.
2. Preformationism theory
• According to this theory
organisms are exist in their
miniature form prior to their
development.
• This miniature form was named
Homunculus (little man).
• For animals, animalcules.
•Preformationism theory harbored two opposite ideas
a) Spermisit preformation theory (spermism)
• According to this theory; fathers contribute
the essential characters of their offspring.
• Mothers contribute to development of
embryo as only supplying nutrients (foods).
• Male contribution is more than female.
• One of the pioneers of this theory is
Pythagoras.
b) Ovist preformation theory (ovism)
• In this theory mathernal contribution is
more than paternal.
• Animal Eggs can constitute an embryo
without a sperma.
3. Epigenesis theory
• This is the opposite theory of
preformationism.
• Epi (above) genesis (formation)
• According to this theory shape and structure
of embryo are not exist before and during
fertilization.
• This structure is slowly evolving through
metamorphosis until birth.
• One of the pioneers of this theory is Aristotle.
Invention of Microscope
• "micro" small, "scope" a tool to
look an object
• It was invented by Robert
Hooke in 1665.
• He examined a slightly cut cork
using microscope.
• And observed some gaps.
• He named these gap as cell.
1635-1703
• Monocular microscope was
invented by Antonie
Leeuwenhoek (Draper, wine
gourmet).
• Leeuwenhoek obseved using
this microscope,
• In 1674 protozoa
• In 1677 erythrocyte
• In 1683 bacteria
• He is known as father of
microbiology.
1632-1723
Cell Theory
• In 1838 Schleiden and Schwann proposed that
all living things were made up cells.
Matthias Schleiden
(1804-1881)
Theodor Schwann
(1810-1882)
Germplasm Theory
• In 1904 August Weismann
proposed that there are two
kind of body cell.
• Somatic cell and Germ cell
• Each portion of the body are
represented in germ cells and
they form next generation (i.e.
inheritance only can takes
place by means of the germ
cells)
1834-1914
Mendel Time
• He is known as the father of
modern genetics.
• He was a priest
• Studied about botanic and physic
at Vienna University between
1851-1853.
• Then he focused on inheritance of
characters in plants.
• Between 1856 and 1863 he
perfomed many hybridization
experiments with pea plant.
Gregor Mendel
1822-1884
Mendel Experiments
• He used pea as model plant and during his
experiments he used about 28.000 pea plant .
• Worked with seven characters
1. Flower color (Purple, White)
2. Flower position (Axial, Terminal)
3. Seed pod color (Green, Yellow)
4. Seed pod shape (Inflated, Constricted)
5. Seed color (Yellow, Green)
6. Seed shape (Round, Wrinkled)
7. Plant height (Tall, Dwarf)
• Every hybridization was performed just for
one or a few number of characters.
• purple flower X white flower (monohybrid)
• tall plant with yellow seed X dwarf plant with
green seed (dihybrid)
• He counted every phenotype obtained from
hybridizations.
• Established many rules of heredity.
• These rules are know as the laws of
Mendelian inheritance.
• In his experiments he observed that
• First cross
(P)
(P)
(F1)
• yellow seed pea X green seed pea = yellow seed pea
• Second cross
• yellow seed X yellow seed = yellow : green (3:1) seeds
• In the second cross the peas having yellow seeds appeared
at a ratio of 3:1 in their phenotype.
• To explain this phenomenon, he coined the terms
dominant and recessive.
Dominant vs Recessive
• All diploid organisms have two sets of chromosomes (Pea,
2n=14).
• One set is inherited maternally other paternaly.
• Every chromosome set have same genes with different
alleles.
• Different alleles of a certain gene can be expressed
unequally.
• In this case an allele that has more impact in phenotype is
dominant while other is recessive.
• Some alleles of a gene can have equal effects.
• If an allele is dominant, it is marked with
uppercase.
• If an allele is recessive, it is marked with
lowercase.
Round pea seed (W), Wrinkled pea seed (w)
• An organism can have two dominant, two
recessive or one dominant and one recessive
alleles (WW, ww, Ww).
Genotype
WW
Ww
ww
Phenotype
Round seed
Round seed
Wrinkled seed
• In his experiments Mendel obseved purple flower
color dominant to white, yellow seed color dominant
to green…
P: Parent (ancestral)
F1: Filial (first generation)
F2: Filial2 (Second generation)
An Example
yellow seed X green seed
(G G)
(g g)
Gg Gg Gg Gg
If F1 generations are crossed
Gg X Gg
(F1: Yellow seeds)
GG Gg Gg gg
Genotype 1
Phenoptype
2
3
1
1
(F2: 3 yellow 1 green)
• Experimental results of Mendel were
published in 1865.
• After all of his experiments Mendel suggested;
– there are some invisible factors which provide
visible (phenotypic) traits (now we call these
factors as gene).
– these factors are exist as two copies.
• Unfortunately his experiment didn't get
attention during that time.
• At that time mathematical analysis and
probability not common in biology.
• His results did not fit well with the most
accepted hypothesis about the source of
diversity among organisms.
• Darwin’s Evolution Theory was more popular.
• About 35 years later his results were
rediscovered.
Evolution Theory
• All species have common
ancestors.
• Speciation is resulted from
natural selection.
• 1859 On the Origin of Species
Charles Robert Darwin
1809-1882
After Mendel
• Friedrich Miescher isolated
nucleic acids from white
blood cells in 1869.
• And identified the chemical
structure of nucleic acids in
1871.
• Walter Flemming (1843-1905)
• Identified cell division process (1882)
• Theodor Boveri (1862-1914)
• He pointed out relation between
chromosomes and inheritance.
• William Bateson (1861-1926)
• Term of Genetics (1909)
• Wilhelm Johannsen (1857-1927)
• Genes are the fundamental unit of
heritable phenotypic traits (1909)
• Thomas Hunt Morgan (1866-1945)
• Genes are on the chromosomes
(1910)
One Gene One Enzyme
• They claimed that genes are
responsible for production of
enzymes.
• One gene can encode one
enzyme (1941)
• In the following time it is proved
that one gen can encode more
than one enzyme by different
way (such as alternative
splicing).
George Welles Beadle
1903-1989
Edward Lawrie Tatum
1909-1975
Discovery of Transposons
• During 1940-1950 McClintock had
worked color variations between
maize seeds.
• She claimed that there are some
movable elements in the genome.
• That time her studies were not
accepted by science society.
• They were skeptical about her
works.
• Because genes were known as
stabil.
• She was awarded with Nobel Prize
in 1983.
Barbara McClintock
1902-1992
• He had worked on base
concentrations in DNA (1949-1951).
• He found that
1. Amount of purine and pyrimidine is
equal (A+G=C+T).
2. Adenine amount is equal with
thymine while guanine with
cytosine (A=T and G=C).
3. Amount of A+T do not have to be
equal with G+C.
Erwin Chargaff
1905-2002
Purine + Pyrimidine = Perfect fit
• A and G are Purine
• T and C are Pyrimidine
A=T
G≡C
• They worked X-ray diffraction.
• With this method they could take
X-ray photographs of DNA (19511953).
• These photos helped to
understand DNA double helix
structure.
Rasalind Elsie Franklind
1920-1958
Maurice H. Wilkins
1916-2004
Discovery of the DNA structure
• In 1953, Structure of DNA was discovered.
• While using Franklind, Wilkins and Chargaff
datas Watson and Crick suggested the double
helix model of DNA.
• They were awarded with Nobel Prize in 1962.
James D. Watson
1928-…
Francis H. Crick
1916-2004
• Discovery of mRNA (1961)
Francois Jacob
1920-2013
Matthew Meselson
1930…
Sydney Brenner
1927…
• Together with Kent W. Wilcox,
Smith discovered restriction
enzymes (1970).
• Isolation and characterization
of these enzymes allowed to
make recombinant DNA
molecules.
Hamilton O. Smith
1931….
DNA sequencing
• He developed a method to
sequence DNA molecules
(1977).
Frederick Sanger
1918-2013
Stem Cell
• 1978: Stem cells were
discovered in human cord blood
• 1981: First in vitro stem cell line
produced from mice
• 1988: Embryonic stem cell lines
created from a hamster
• 1995: First embryonic stem cell
line derived from a primate
• Today stem cell works have been
continuing in many area of
medicine for diseases
treatments.
First Transgenic Mouse
• Transgenic organisms
have a gene from an
other organism.
• Naturally don't exist.
• They are produce in
laboratuvar conditions.
Polymerase Chain Reaction
• He improved PCR technique (1986).
Kary Banks Mullis
1944…
Genome Projects
•
•
•
•
•
•
•
•
Saccharomycetes (1996)
Nematode (1998)
Fruit Fly (2000)
Arabidopsis (2000)
Microsporidium (2001)
Mosquito (2002)
Rice (2002)
Human (2006)
Dolly was Cloned
• Dolly is the first
mammalian that was
cloned (1996-2003).
Synthetic Genomics
• DNA frangments were
chemically synthesized.
• In 2006 J. Craig Venter and his
colleagues had constructed a
synthetic genome of a
bacterium.
• Mycoplasma laboratorium
What is Genetics?
• Genetics is a
multidisciplinary science
that study about genes,
variations and heredity in
organisms.
• Related with cell,
organism and their
offspring, population etc.
Genetic Material
• Genetic material is Nucleic Acids.
• Nucleic acids are polymeric
macromolecules.
• Units of these macromolecules are
nucleotides.
• There are two kind of nucleic acids.
1. DNA (Deoxyribonucleic acid) is genetic
material of all living organisms.
2. RNA (Ribonucleic acid) is the genetic
material of some viruses.
Genetic material must have 4 criteria
1. Information; the genetic material must contains the
information that necessary to construct of an entire
organism.
2. Transmission; the genetic material can be passed from
parent to offspring.
3. Replication; the genetic material must be accurately
copied
4. Variation; the genetic material must have diversity as is
found in the innumerable forms of life.
Identification of DNA as The Genetic
Material; Experiments of Frederick Griffith
• Frederick Griffith formed a basis to prove the DNA as
genetic material.
• He choosed 2 strains of Diplococcus pneumoniae.
• IIIS strain (virulent) has a polysaccharide capsule and
produce smooth colonies.
• IIR strain (avirulent) do not have capsule and produce
rough colonies.
• Using these bacterial strains he performed an
experiment.
Griffith’s Conclusions
Something from the dead type IIIS
bacteria, transformed type IIR into type
IIIS bacteria.
Called this process transformation
Identification of DNA as The Genetic Material;
Avery, MacLeod and McCarty Experiments
• There are 4 categories of biomolecules in the cells.
1. Nucleic acids (DNA and RNA).
2. Proteins
3. Carbohydrates
4. Lipids
• Each of these biomolecules were candidate to be
genetic material.
• In 1944 Avery, MacLeod and McCarty used enzymes
to hydrolyse this molecules.
Identification of DNA as The Genetic Material;
Avery, MacLeod and McCarty Experiments
• They homogenized and filtered virulent IIIS type
bacteria to obtain a mixture of proteins, lipids, DNA,
RNA and carbohydrates.
• Then they divided his mixture into 5 tubes.
• They added one of the enzymes that hydrolyze the a
biomolecule, on each tube.
• Then the mixtures were mixed avirulent IIR type
bacteria.
• After cultivation, IIR type bacteria were injected to the
mice.
• And they observed only the mouse that injected with
DNaz enzyme containing mixture, was alive.
• They concluded that DNA is genetic material.
Identification of DNA as The Genetic Material;
Avery, MacLeod and McCarty Experiments
Identification of DNA as The Genetic Material;
Hershey and Chase Experiments
• Hershey and Chase confirmed the DNA as
genetic material by using T2 phage (a virus)
and radioisotopes of phosphorus and
sulphur.
• Phosphorus exist in DNA while sulphur in
proteins.
• They marked DNA and proteins with
radioisotopes of phosphorus and sulphur.
• Phage T2
Life cycle of phage T2
• They used radioisotopes of phosphorus
and sulphur to distinguish DNA from
proteins.
– 32P labels DNA specifically
– 35S labels protein specifically
• Infect non-radioactive E. coli with
radioactively-labeled phages.
• Remove phage coats from cells.
• Is the 32P or 35S inside bacteria?
s
Nucleic acids
• Nucleic acids are polymeric macromolecules.
• Nucleic acids are large organic compounds found
in the chromosomes of living cells and viruses.
• They are strong acids found in the nucleus of the
eukaryotic cells and cytoplasm of prokaryotic
cells.
• Units of these macromolecules are nucleotides.
• Two types of nucleic acids are deoxyribonucleic
acid (DNA) and ribonucleic acid (RNA).
Function of nucleic acids
1. The main function of DNA is the storage
genetic information.
2. Allow organisms to transfer genetic
information from one generation to the next
(DNA).
3. Genetic variations (DNA).
4. RNA is essential for the protein synthesis.
5. RNA also a structural conponents of
ribosomes.
Structure of Nucleotide
• Nucleotides are the unit of nucleic acids.
• Contain phosphate group, pentose sugar (5
carbon) and a base (A, G, T, C or U).
Deoxyribonucleotide
Ribonucleotide
base
phosphate group
Pentose sugar
Polymerization of Nucleotides
• The 3' hydroxyl group attacks the 5’
triphosphate group an other nucleotide.
• A new phosphodiester bond is formed, and a
pyrophosphate group leaves.
Polymerization of Nucleotides
• This polymerization
is elongated through
5’-3’ direction and
one strand of DNA is
formed.
Bases of DNA and RNA
• Nucleobases
contain nitrogen.
• Purines
have double-ring
while pyrimidines
one.
• Thymine and Uracil
are identical except
methyl group at 5’C.
Base pairing
• The A-T and C-G
pairings are required to
match the hydrogen
bonds.
• A-T pair have two
hydrogen bonds while
G-C have three.
Three dimensional α-helix structure of DNA
What is Gene?
• Gene is a molecular unit of living
organisms.
• Usually a DNA fragment. In viruses
sometimes RNA.
• Genes hold the information and encode
proteins that needed for biological
processes, to build and maintain an
organism's life.
Where is Gene?
Eukaryotic cell
Prokaryotic cell
Structure of Genes
A gene contains
1. Promoter (regulatory region)
2. Coding region (Exons and introns)
3. Termination site (stop)
• Also interact with cis and trans acting
elements.
1. Eukaryotic gene structure
• Promoter initiates transcription of a particular
gene and locates near the transcription start
sites.
• Coding region encodes a protein.
Exons and introns
• Terminator has some marks to terminate of a
gene transcription.
• Eukaryotic genes are usually monocistronic.
2. Prokaryotic gene structure
• In the prokaryotes genes related with same
pathway, have common promoter and
operator region.
• In other word polycistronic.
• Contain less or no introns.
Number of genes
• Are there any correlation between gene
numbers and organism?
• Do more complex organisms have much
genes?
Allele
• Allele (allelomorph) : other
form
• Alleles are the alternative
(variant) forms of the same
gene.
• These variant forms of a
gene can cause different
phenotypes.
• Such as skin, hair and eye
colors etc.
• Most common allele is
known as wild type.
• Generally multicellular organisms have two
sets of chromosomes (diploid).
• One set inherited from mother and other from
father and they are named as homologous
chromosomes.
• Every chromosome set have same genes with
different alleles.
• Different alleles of a certain gene can be
expressed unequally or equally.
• In the first case an allele that has more effect in
phenotype is dominant while other is recessive.
• In the second case both alleles phenotypes
appear and it is mentioned with co-dominance.
• If phenotype is appear as intermediate form this
case is called incomplete dominance.
Codominant and Incomplete dominant
Codominant
R1R1
Incomplete dominant
R2R2
R1R2
R1R1
R2R2
R1R2
A gene can have more than two
alleles (Multiple alleles)
• The best example is ABO blood type
carbohydrate antigens.
• An individual can have one of six possible
genotypes (IAIA, IAIO, IBIB, IBIO, IAIB, IOIO).
• These genotypes cause four phenotypes (A, B,
AB, O).
Alleles are formed by mutations
• Mutation is a change of the nucleotide
sequence of DNA.
• It may be positive, negative, or neutral.
• There are many reasons for mutation. These
can be classified as internal and external
factors.
What is Genome?
• Genome is the complete set of an
organism’s DNA, including all of its genes.
• Both genes and non-coding DNA
sequences.
• In some viruses genome is the all
sequences of RNA.
• Not only nuclear genes, but also include
cytoplasmic and organelle DNA
(mitochondria and chloroplast DNA).
Genome Sizes
• Are there any
correlation
between
genome size and
organism?
• Do more
complex
organisms have
high amount of
DNA?