McClintock 19021992 An American scientist and cytogeneticist who was awarded the 1983 Nobel Prize in Physiology She received her PhD from Cornell University in 1927 She studied ID: 916529
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Slide1
DNA Reccombination
Slide2Barbara
McClintock, (1902–1992)
An
American scientist and
cytogeneticist
who was awarded the 1983
Nobel Prize in
Physiology.
She received her
Ph.D
from
Cornell University
in
1927. She studied
chromosomes
and
how they change during reproduction in maize.
One
of those ideas was the notion of
genetic recombination
by
crossing-over
during
meiosis
—a mechanism by which chromosomes exchange information. She produced the first
genetic map
for maize, linking regions of the chromosome to physical traits. She demonstrated the role of the
telomere
and
centromere
, regions of the chromosome that are important in the conservation of
genetic information
. She was recognized among the best in the field, awarded prestigious fellowships, and elected a member of the
National Academy of Sciences
in 1944.
Slide3Robin Holliday
(1932-2014)
A
British
molecular
biologist
.
Holliday described a mechanism of DNA-strand exchange that attempted to explain gene-conversion events that occur during meiosis in fungi. That model first proposed in 1964 and is now known as the
Holliday
Junction
.
In 1975 he suggested that DNA methylation could be an important mechanism for the control of gene expression in higher organisms, and this has now become documented as a basic
epigenetic
mechanism in normal and also cancer
cells.
Slide4A
Holliday intermediate formed between
two bacterial
plasmids in vivo, as seen with
the electron
microscope
.
Note that such intermediates can form only when the nucleotide sequences of the two parental duplexes are very similar or identical in the region of recombination because specific base pairs must form between the bases of the two parental duplexes.
Slide5Recombination
Two DNA molecules can recombine with each other to form new DNA molecules that have segments from both parental molecules.
Slide6Classes Of Recombination
1
.
Homologous genetic recombination
(also called general recombination)
This involves genetic exchanges between any two DNA molecules (or segments of the same molecule) that share an extended region of nearly identical sequence. The actual sequence of bases is irrelevant, as long as it is similar in the two DNAs.
Slide72.
S
ite-specific recombination :
The exchanges occur only at a particular DNA sequence.
3
.
DNA transposition :It is usually involves a short segment of DNAwith the remarkable capacity to move from
one location in a chromosome to another.
These
“jumping genes”
were first observed
in maize in the 1940s by Barbara McClintock.
Slide8Functions of genetic recombination
1. They include roles in specialized DNA repair systems.
2. Specialized activities in DNA replication.
3. Regulation of expression of certain genes.
4. Facilitation of proper chromosome segregation
during eukaryotic cell division.
5. Maintenance of genetic diversity in a population.
6. Implementation of programmed genetic
rearrangements during embryonic development.
Slide9Recombination during meiosis
Model of double-strand break repair
for homologous
genetic recombination. The
two homologous
chromosomes involved in this recombination event have similar sequences.Each of the two genes shown has different
alleles on
the two chromosomes. The DNA strands
and alleles are colored differently so that their fate
is evident
.
Slide10Slide11Slide12Replication
Prophase I
separation of
Homologous pairs
first
Meiotic division
second
Meiotic division
Haploid gametes
Meiosis in eukaryotic germ-line cells.
Diploid
germ-line cell
Slide13DNA recombination
In
meiosis homologous pair of chromosomes are arranged in pairs, so
that each
chromosome with two parental sister chromatids are facing each others
in this
arrangement to give a special tetrad arrangement of 4 chromatids .In this arrangement, the opposite chromatids which come from each chromosome will undergo a process
of crossover
. That is opposite
chromatids exchange pieces of DNA between each
others
.
Slide14DNA recombination
Exchange
of DNA
which allows mixing of genetic information between gametes
that originate from father and mother and produces new combinations of genes. Without this phenomenon, the new gametes will have exactly the same genetic information as the original parents and no genetic variations occur.
Slide15Recombination involves the breakage and rejoining of two chromosomes (M and F) to produce two re-arranged chromosomes (C1 and C2).
Slide16Crossing
over. (a)
Crossing over often produces an
exchange of genetic material.
(b)
The homologous chromosomes of
a grasshopper are shown during prophase I of meiosis. Many points of joining (
chiasmata
) are evident between the two homologous pairs
of chromatids. These
chiasmata
are the physical manifestation of
prior homologous
recombination (crossing over) events.
Slide17Recombination of the V and J
gene segments of the human IgG
kappa light
chain.
Slide18The light chain can combine
with any of 5,000 possible
heavy
chains to produce an
antibody molecule
Slide19Slide20Slide21Slide22Chromosome
is highly folded form of the interphase chromatin (extended or relaxed threads of the same nucleoprotein structure).The chromosome form appears during cell division, particularly in the metaphase stage.
Slide23Chromatin present in two forms
Euchromatin
: the part of chromatin that, during
interphase
, are uncoiled (decondensed) and non-
stained
but containing high concentrations of
transcribed genes (
transcriptionally active)
2. Heterochromatin: The part of the chromatin that
remains
tightly coiled (condensed) and intensely
stained
during interphase, but inactive in gene
expression
.
Slide24Yeast is known as
Saccharomyces cerevisiae
, which is the single-celled
fungus used to make bread. Yeast is haploids with a genome of 16 chromosomes single
set
.
The gene for mating has a locus on one chromosome which makes the yeast exists either in dominant mating type (G) or recessive mating
type
(g
).
Slide25The yeast has two types of cell division,
asexual in which the cell divide to produce
two haploid cells with the same mating type
. A
second type of
cell division
called sexual in which two cells conjugate together during mating toproduce new hybrid cell .The hybrid cell is a diploid having pair of two alleles, similar to the pair of alleles arrangements in diploid system of human
cells.
Slide26Slide27In diploid system
The
gene is responsible for certain trait in phenotype expression(color of
eyes, color
of skin
).
The allele is a variant of the gene (in eye color expressed as black or
brown
or
blue
) so that certain people have a specific allele of
that gene
, which results in the trait variant. The genes code for proteins,
which might
result in different traits, but it is the
gene
, not the trait, which is inherited
Slide28Behavior of 2 different genes at different positions on the same chromosome
When
chromosomes go through meiosis, there are two possible situations:
If
no cross-over between the two gene loci
occurs
(if they are present in short distance from
each
other' on the same chromosome):
-
Alleles segregate
together
on the same
chromosome
- A and B together and a and b
together
2. If there is a cross-over between the two gene
loci (
when they are present far distance from each other's on the
chromosome).
Slide29Alleles
segregate from each other in Meiosis II
Two recombinant products:
- A and b now together in one meiotic product
- a and B now together in one meiotic product
Two parental products
the other two meiotic products are still AB and ab
Slide30Slide31Slide32Gene
density
Not
all the DNA genome encodes protein, but usually it contains coding
and non-coding
sequences. The percentage of coding sequence in total genome
is called gene density.In bacteria the gene density is about 90 % .
In human this density is only about 2% .
Slide33Therefore, majority of eukaryotes DNA contain non-coding DNA, or regions of DNA that serve no obvious function. Simple single-celled eukaryotes have relatively small amounts of such DNA, whereas the genomes of complex multicellular organisms, including humans contain an absolute majority of DNA without an identified function.
Slide34This non-coding sequences include repetitive DNA sequence (satellite DNA) , introns and regulatory regions which occupies 98% of total human genomic DNA.
The genomic non-coding DNA sequences are components of an organism's DNA that do not encode protein sequences. Some noncoding DNA is transcribed into functional noncoding RNA molecules (e.g. transfer RNA, ribosomal RNA, and regulatory RNAs), while others are not transcribed or give rise to RNA transcripts of unknown function.
Slide35Functions of noncoding DNA
1
. Protection of the genome:
Noncoding DNA separate genes from each other with long gaps, so alteration in one gene or part of a chromosome does not extend to the whole chromosome. In high genomic complexity like in case of human genome, not only different genes, but also inside one gene there are gaps of introns to protect the entire coding segment to minimize the changes caused by changing part of the
gene.
Slide362. Genetic switches:
Some noncoding DNA sequences function as genetic switches that decide when and where genes are expressed.
3. Regulation of gene expression:
Some noncoding DNA sequences quantitatively determine the expression levels of various genes.
Slide374. Act as regulatory sites for gene actions:
Some non-coding sequence can be promoters, operators, and enhancers ….etc.
Repeated sequences are patterns of DNA that occur in multiple copies throughout the genome.
Slide38Satellite
DNA
Very
large sequence consists of tandem repeating, non-coding DNA. It is the main component of functional centromeres, and forms the main structural constituent of heterochromatin. A repeated pattern can be between 1 base pair long (a mononucleotide repeat) to several thousand base pairs long, and the total size of a satellite DNA block can be several
mega bases
(Unit of length for DNA fragments equal to 1 million nucleotides and roughly equal to 1
cm)
without interruption.
Slide39Most satellite DNA is localized to the
telomeric or the
centromeric
region of the chromosome. The nucleotide sequence of the repeats is fairly well conserved across a species. However, variation in the length of the repeat is common. The difference in how many of the repeats are present in the region (length of the region) is the basis for DNA fingerprinting in forensic medicine.
Slide40Tandem repeats
: copies which lie adjacent to each other, either directly or inverted
Minisatellite
- repeat units from about 10 to 70 base pairs, found in many places in the genome, including the centromeres.Microsatellite
- repeat units of less than 10 base pairs (typically have 6 to 8 base
repeat units) mainly found in telomeres
Slide41Some types of satellite DNA in humans are
Type
Size of repeat unit (
bp
)
Location
α (
alphoid
DNA)
171
All chromosomes
β
68
Centromeres of chromosomes 1, 9, 13, 14, 15, 21, 22 and Y
Mini-satellite
25-48
Centromeres and other regions in heterochromatin of most chromosomes
Micro-
satalite
5
Most chromosomes
telomers