Download highly repetitive DNA

Genome size increases (roughly) with
evolutionary complexity of organism
Organism
Virus MS2
Virus l
50
Other viruses
Bacteria
Genome (kb)
4
5-300
700-5000
Form
RNA
Linear DNA
Circular DNA
Circular DNA
Yeast
Arabidopsis (plant)
Fruit fly
Mouse
Human
13,000
100,000
165,000
3,000,000
3,000,000
Linear DNA
arranged
as
several
chromosomes
Supercoiling of DNA
• The tension induced in a circular DNA molecule
causes it to become supercoiled
• Supercoiling is the usual state for bacterial
chromosomes, which consist of a number of
independently supercoiled loops
• The process is controlled by topoisomerase
enzymes that can cut and re-join one strand of the
DNA
• Topoisomerases can also untangle DNA
• Refer to figures 6.1 and 6.4 in Hartl
Eukaryotic chromosomes
• In metaphase of mitosis, chromosomes can be seen under microscope they have a compact rod-like structure
• The ends of chromosome are called telomeres, function is to protect
the ends of the DNA
• Near the middle is the centromere, function is to attach to spindles
during cell division and ensure correct segregation
• Telomeres and centromeres contain special DNA sequences and
associated proteins
• Telomeres are replicated differently from the rest of the genome - see
figure 6.27 in Hartl
• Different regions of the chromosome can be stained with dyes (e.g.
Giemsa) giving a characteristic banding pattern
• See figure 6.20 in Hartl
Chromosome structure - packing ratio
• Packing ratio is the length of the DNA divided by
the length into which it’s packaged
• Smallest human chromosome (21) has 4x107 bp of
DNA, 10 times size of E. coli genome
• Equivalent to 14mm of extended DNA
• In most condensed state the chromosome is about
2mm long
• Packing ratio = 14000/2 = 7000
• So, there must be an efficient packaging
mechanism
Chromatin and histones
• The first level of DNA packing is the chromatin fibre
• Chromatin is formed by wrapping the DNA around
complexes of the 4 histone proteins (2 molecules each of
histones H2A, H2B, H3, H4) to form “beads on string”
arrangement
• Chromatin is of 2 different types - euchromatin (where
most of the active genes are) and heterochromatin (no
active genes). Some regions of genome can switch
between these 2 states (facultative heterochromatin)
• See figure 6.8 in Hartl
Higher level DNA packing
• To achieve packing ratio of 7000, chromatin
is organised into several levels of complex
folded and coiled structures
• See figure 6.10 in Hartl
Unique and repeated DNA
• If eukaryotic DNA is melted and allowed to
re-anneal, it does so in 3 distinct phases
• See figure 6.18 in Hartl
• The explanation is that there is highly
repetitive DNA (which re-anneals quickly),
moderately repetitive DNA (intermediate)
and unique or single copy DNA (re-anneals
slowly)
Classes of eukaryotic DNA
• Highly repetitive:
– Bits of old virus genomes
– Simple sequence repeats e.g. CACACA….
– Special sequences such as centromeres
• Moderately repetitive:
– Other old virus genomes
– Multi-gene families, e.g. ribosomal RNA
• Single-copy:
– Most “normal” genes
Stability of genomes
• Most DNA is very stable - inherited without changes from parents
(except 1/106 mutation rate) and does not change in the lifetime of the
cell
• Some DNA is unstable, i.e. can move about in the genome - called
transposable elements or transposons
• First observed by Barbara McLintock in the 1940s, as different
coloured segments in corn cobs (see section 6.8 in Hartl)
• Explanation was transposon in the maize genome that affects
expression of genes controlling pigment - jumps to different locations
in DNA of different segments of the corn-cob, switching colour in
those segments
• Many other examples, in many organisms (including humans). Often
they are repetitive in the genome