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Genome structures
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C-value paradox: no correlation between complexity of an organism and genome size.
Table 7.2 Genomes 3 (© Garland Science 2007)
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Genome of Fritillaria ≈ 40 times larger than human genome.
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There is an increase in the number of introns and of repeat sequences going from bacteria to “lower” and “higher” eukaryotes.
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Schematic of RNA splicing in eukaryotes.
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A processed pseudogene
Figure Genomes 3 (© Garland Science 2007)
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Figure 7.21 Genomes 3 (© Garland Science 2007)
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There is an increase in the number of introns and of repeat sequences going from bacteria to “lower” and “higher” eukaryotes.
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Repetitive DNA in genomes
Mostly DNA and RNA transposons Repetitive DNA Tandemly repeated DNA is in the centromere (satellite DNA), the telomeres (minisatellites), and microsatellites. Genome-wide repeats: Retroelements (LTRs, LINEs, SINEs) and DNA transposons. Make up about 46% of the human genome. Tandem repeat means that the same sequence is repeated many times in the same position. The length of the repeated sequence can be one to a few base pairs (as in microsatellites) up two more than 100 bp (as in satellite DNA in centromeres). Tandem repeats are not genome-wide repeats because they do not occur in other places of the genome. Satellite DNA (micro-, mini-, satellites)
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Microsatellite analysis (24 samples)
Microsatellites on the short arm of human chromosome 6 amplified by PCR. Blue or green marker. Red bands are size markers. 24 samples. Apparently 12 different microsatellites amplified by PCR. In US 13 microsatellites are used for this type of genetic profiling, in the UK 10. Figure Genomes 3 (© Garland Science 2007)
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Chromatin organization
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Bacterial chromosomes are generally negatively
supercoiled and associated with a number of proteins, primarily HU proteins
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Eukaryotic nuclear chromosomes are negatively
supercoiled by association with histone proteins
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Origin of replication General features of eukaryotic chromosomes
Only 1 origin of replication in bacterial genomes. Eukaryotes have multiple origins of replication, about 1 every to bp.
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Centromeres are necessary for correct segregation of
chromosomes to daughter cells in cell division Centromeres associate with proteins to form kinetochores, i.e. attachment sites for microtubules
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Centromeres vary in size. Most consist of tandem repeats.
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Origin of replication General features of eukaryotic chromosomes
Only 1 origin of replication in bacterial genomes. Eukaryotes have multiple origins of replication, about 1 every to bp.
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Telomeres consist of tandemly repeated DNA
(minisatellites) at the ends of chromosomes. They maintain the ends of linear chromosomes. 5’-TTAGGG-3’ is the repeat unit in humans.
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Chromatin organization is not fixed
Cell cycle
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Chromatin organization is not fixed
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Chromatin organization is not fixed
Cohesin- and condensin protein complexes induce formation of M phase chromosomes.
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Chromatin organization is not fixed
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Proteolysis of cohesins allows segregation of sister chromatids.
Condensins Cohesins Proteolysis of condensins leads to interphase chromosomes.
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Mitosis Meiosis
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Chromatin organization is not fixed
Interphase M-phase
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General organization of interphase
chromatin in the nucleus
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Nucleosomes
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Histones are the core proteins of nucleosomes
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Histones are the core proteins of nucleosomes
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Histones are the core proteins of nucleosomes
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Histones are the core proteins of nucleosomes
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Assembly of nucleosomes is promoted by histone chaperones
Proliferating cell nuclear antigen (PCNA) = sliding clamp
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Assembly of nucleosomes is promoted by histone
chaperones
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Histone H1 is a linker histone
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Structural changes in nucleosome positioning
in the presence of linker histone H1 + H1 no H1
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General organization of interphase
chromatin in the nucleus
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Possible organization of the 30 nm fiber
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Histone core modifications:
CENP-A can replace histone H3 in centromeres. H2A and H2B variants are also found in histone cores.
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General organization of interphase chromatin in the nucleus
Euchromatin, heterochromatin
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Histone tail modifications
influence chromatin structure
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Histone modifying protein complexes
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Histone tail modifications alter chromatin structure
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Histone tail modifications cause changes
in chromatin structure loose tight
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Histone tail modifications create binding
sites for protein complexes that alter the structure of chromatin
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Nucleosome remodeling complexes alter the
position of nucleosomes
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Nucleosome remodeling complexes alter the
position of nucleosomes
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DNA methylation alters chromatin structure
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Genomic imprinting
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