Genome structures
C-value paradox: no correlation between complexity of an organism and genome size. Table 7.2 Genomes 3 (© Garland Science 2007)
Genome of Fritillaria ≈ 40 times larger than human genome.
There is an increase in the number of introns and of repeat sequences going from bacteria to “lower” and “higher” eukaryotes.
Schematic of RNA splicing in eukaryotes.
A processed pseudogene Figure 7.20 Genomes 3 (© Garland Science 2007)
Figure 7.21 Genomes 3 (© Garland Science 2007)
There is an increase in the number of introns and of repeat sequences going from bacteria to “lower” and “higher” eukaryotes.
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)
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 7.24 Genomes 3 (© Garland Science 2007)
Chromatin organization
Bacterial chromosomes are generally negatively supercoiled and associated with a number of proteins, primarily HU proteins
Eukaryotic nuclear chromosomes are negatively supercoiled by association with histone proteins
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 30 000 to 200 000 bp.
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
Centromeres vary in size. Most consist of tandem repeats.
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 30 000 to 200 000 bp.
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.
Chromatin organization is not fixed Cell cycle
Chromatin organization is not fixed
Chromatin organization is not fixed Cohesin- and condensin protein complexes induce formation of M phase chromosomes.
Chromatin organization is not fixed
Proteolysis of cohesins allows segregation of sister chromatids. Condensins Cohesins Proteolysis of condensins leads to interphase chromosomes.
Mitosis Meiosis
Chromatin organization is not fixed Interphase M-phase
General organization of interphase chromatin in the nucleus
Nucleosomes
Histones are the core proteins of nucleosomes
Histones are the core proteins of nucleosomes
Histones are the core proteins of nucleosomes
Histones are the core proteins of nucleosomes
Assembly of nucleosomes is promoted by histone chaperones Proliferating cell nuclear antigen (PCNA) = sliding clamp
Assembly of nucleosomes is promoted by histone chaperones
Histone H1 is a linker histone
Structural changes in nucleosome positioning in the presence of linker histone H1 + H1 no H1
General organization of interphase chromatin in the nucleus
Possible organization of the 30 nm fiber
Histone core modifications: CENP-A can replace histone H3 in centromeres. H2A and H2B variants are also found in histone cores.
General organization of interphase chromatin in the nucleus Euchromatin, heterochromatin
Histone tail modifications influence chromatin structure
Histone modifying protein complexes
Histone tail modifications alter chromatin structure
Histone tail modifications cause changes in chromatin structure loose tight
Histone tail modifications create binding sites for protein complexes that alter the structure of chromatin
Nucleosome remodeling complexes alter the position of nucleosomes
Nucleosome remodeling complexes alter the position of nucleosomes
DNA methylation alters chromatin structure
Genomic imprinting