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Genome Organisation II
• Eukaryotic genomes are completely different in
their organisation compared to prokaryotic, and
also much bigger
• Their genes are mostly “split” into exons and
introns
• It is not certain which came first in evolution genes with introns/exons or genes without
• Exons may allow evolution of proteins in a
“modular” way
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 26.37 in Lehninger
• Different regions of the chromosome can be stained with dyes (e.g.
Giemsa) giving a characteristic banding pattern
Eukaryotic chromosome structure
Genes, repeated sequences,
replication origins
(mostly euchromatin)
Centromere
(heterochromatin)
Telomeres
(heterochromatin)
(Figure 24-3 Lehninger)
The problem of telomere
replication
Telomere replication
Centromeres
• The centromere is essential for
correct segregation of
chromosomes during cell
division, by attachment to
spindles
• Centromere consists of a small,
core DNA sequence (AT rich)
and specific proteins
• In many species (e.g. humans)
this is flanked by 100s of copies
of a tandemly-repeated sequence
Unique and repeated DNA
• If eukaryotic DNA is melted and allowed to
re-anneal, it does so in 3 distinct phases
• 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)
DNA melting
Classes of DNA
• Mammalian DNA contains 3 main classes of DNA
sequence, as measured by Cot curves:
• Highly repeated DNA (up to 1 million copies)
• Moderately repeated DNA (up to 100,000 copies)
• Unique sequence DNA (strictly speaking 1 copy,
but in practice this also includes sequences with
only a few copies)
Origins and function of DNA classes
• 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
Types of repeated DNA
Ribosomal RNA genes
DNA fingerprinting
• An application of repeated
DNA sequences found in
mammalian genomes
• Highly variable between
individuals
• No 2 people are the same,
except identical twins
Disease caused by a repeat DNA
sequence
• Mutations in the low-density
lipoprotein receptor gene
(LDLR) are a common
genetic cause of heart
disease due to
hypercholesterolemia.
• The LDLR gene is 45kb
long with Alu (highlyrepetitive class) repeats in its
introns. Recombination
between 2 of these leads to a
truncated gene and defective
protein.
CpG islands
• Vertebrate DNA has not much
…CG… because it is mostly
methylated and mutates to
…TG...
5-methyl-cytosine Thymine
• But there are short (1-3kb)
stretches rich in C, G, …CG…
without methylation
CpG islands
• CpG islands are found
at 5’ ends of many
genes
• Unlike rest of genome
they do not bind the
MeCP2 protein
• MeCP2 acts as a
general repressor of
transcription