Transcript molecular biology and genetics

MOLECULAR BIOLOGY – Basic Genetics
MOLECULAR BIOLOGY AND GENETICS
[email protected]
1. Genetic basis
2. DNA structure and genetic code
3. Cell division, replication and transcription
4. RNA processing
5. Regulation of gene expression
6. Translation, function of proteins
7. DNA variation – mutations and repair
8. Recombinant DNA
9. PCR, sequencing, genomics
10. Gene expression analysis
11. Protein analysis, proteomics
MOLECULAR BIOLOGY – Basic Genetics
GENETIC BASIS OF LIFE
MOLECULAR BIOLOGY – Basic Genetics
November 24th, 1859:
CENTRAL PROPOSITION OF EVOLUTION
All living forms origin in common ancestors, they
can change and give rise to new species.
Darwin
2 major concepts:
1. Closely related species share common ancestor
2. Natural selection is a mechanism for evolution
Wallace
MOLECULAR BIOLOGY – Basic Genetics
THEORY OF EVOLUTION
new questions:
1. More progeny is born and some characters
(advantageous) are more likely to be passed
to the next generation.
HOW ARE THE CHARACTERS INHERITED?
2. There has to be variability in populations so that
the natural selection has the pool to select from.
WHAT IS THE SOURCE OF VARIABILITY?
MOLECULAR BIOLOGY – Basic Genetics
Johann Gregor Mendel
(*1822 - †1884)
Augustinian monastery in Brno
MOLECULAR BIOLOGY – Basic Genetics
Mendel picked 7 characters which existed in 2 forms:
He made „true-breeding varieties“
all individuals present in one form
or the other for number of generations
MOLECULAR BIOLOGY – Basic Genetics
Anthers
Pollen
Carpel
amputated anthers
MOLECULAR BIOLOGY – Basic Genetics
P
F2
F1
MOLECULAR BIOLOGY – Basic Genetics
Mendel’s first experiment
Mendel:
5 474
1 850
MOLECULAR BIOLOGY – Basic Genetics
Mendel’s interpretation of his results
1. Each form of a character is controlled by certain heritable factor
2. Obtained results are best explained by the existence of factors in pair
3. Each parent passes to progeny only one of its two factors for the character
MAIN CONCEPT OF HEREDITY arising from Mendel’s work
relationship between gene and allele
CHARACTER = GENE
FACTOR = ALLELE = certain form of character
MOLECULAR BIOLOGY – Basic Genetics
DOMINANT and RECESSIVE
factors (alleles)
HOMOZYGOTES
and HETEROZYGOTES
GENOTYPE and PHENOTYPE
1:2:1
3:1
Random segregation of alleles
MOLECULAR BIOLOGY – Basic Genetics
For Mendel genes were just a theoretical entity
What is a physical essence of the inherited factors?
How are they copied, transmitted and expressed?
MOLECULAR BIOLOGY – Basic Genetics
Zell-substanz, Kern und Zelltheilung (1882)
Walther Flemming
MOLECULAR BIOLOGY – Basic Genetics
1. Chromosomes show specific forms and sizes
2. Number of chromosomes is characteristic for each species
3. In most plants and animals chromosomes were present
in pairs
in agreement with Mendel’s observation about heredity
INTEGRATION OF CYTOLOGY AND GENETICS - CYTOGENETICS
1902-1903 four cytogeneticists independently formulated a concept:
„Mendel’s laws of inheritance are direct consequences of organization
and behavior of chromosomes“
MOLECULAR BIOLOGY – Basic Genetics
PROBLEMS TO ACCEPT CHROMOSOME THEORY OF INHERITANCE
It was obvious that there is more genes than chromosomes.
How is then possible that the genes do not „travel“ with chromosomes?
(Mendel was lucky to pick each factor on different chromosome)
Nobody observed that a certain gene would travel from generation
to generation together with certain chromosome.
MOLECULAR BIOLOGY – Basic Genetics
Thomas Hunt Morgan
(1866-1945)
1910
Drosophila melanogaster
MOLECULAR BIOLOGY – Basic Genetics
P
X
YX
F1
XX
X
YX
XX
F2
YX
YX
XX
XX
MOLECULAR BIOLOGY – Basic Genetics
yellow
white
miniature
MOLECULAR BIOLOGY – Basic Genetics
FIRST SUMMARY – CRUCIAL KNOWLEDGE
MOLECULAR BIOLOGY – Basic Genetics
cytoplasm
Gene X in diploid cell
nucleus
Pair of homologous
chromosomes,
one from father,
one from mother
allele X1
protein X1
allele X2
protein X2
MOLECULAR BIOLOGY – Basic Genetics
Somatic line
Mitosis
Genetic information is not mixed
both progeny cells are genetically
the same as the parental cell
MOLECULAR BIOLOGY – Basic Genetics
grandmother A
grandfather A
grandmother B
MOTHER
grandfather B
FATHER
Recombination
between pairs
of homologous
chromosomes
from grandmother A
from grandfather B
from grandfather A
from grandfather B
MOLECULAR BIOLOGY – Basic Genetics
GENES ARE ON CHROMOSOMES
proteins
DNA
MOLECULAR BIOLOGY – Basic Genetics
Frederick Griffith (1871 - 1941)
MOLECULAR BIOLOGY – Basic Genetics
1928 – Griffith’s experiment
TRANSFORMATION OF GENETIC MATERIAL
MOLECULAR BIOLOGY – Basic Genetics
What was the transformation factor?
1944
Oswald T. Avery
Colin M. MacLeod
Maclyn McCarty
Rockefeller Institute for Medical Research, New York
MOLECULAR BIOLOGY – Basic Genetics
TRANSFORMATION
FACTOR
MOLECULAR BIOLOGY – Basic Genetics
Bacteriophage infecting E.coli
MOLECULAR BIOLOGY – Basic Genetics
Martha Chase a Alfred Hershey - 1952
MOLECULAR BIOLOGY – Basic Genetics
35S
32P
32P
32P
32P
32P
35S
DNA
Methionin
MOLECULAR BIOLOGY – Basic Genetics
Hershey-Chase experiment
MOLECULAR BIOLOGY – Basic Genetics