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Lecture 10
Genes, genomes and chromosomes
Repeated and transposable elements
What if microstates are occupied unequally? How to write the entropy?
S  k lnW
S
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k
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 p ln p
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p – probabilities of states
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lattice position
S = min
Show this!
S = max
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E. coli
S. cerevisiae
C. elegans
A. thaliana
D. melanogaster
M. musculus
H. sapiens
Caryotype of H. sapiens
4.5 Mb
16 Mb
100 Mb
125 Mb
180 Mb
3200 Mb
3300 Mb
1 circular chromosome
16 (haploid set)
6
5
4
20
Chapter
23
6
Chromosomal organization
Genomes of many organisms contain large amount of ‘nonfunctional’ DNA
E. coli
Yeast
Fruit fly
Chicken
Human
4.5 Mb
12 Mbases/haploid set
180
1300
3300
Tulips
~30000 Mbases
Amoeba
~660,000 Mbases/nucleus
1
16 chromosomes
4
39
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The DNA contents does not reflect the complexity of the organism!
Related and structurally similar species may have variation in the
amount of their total DNA by a factor of 100
In humans: ~5% of DNA is transcribed and 1.5% represents
coding regions (exons). The rest is made of repeats with no
obvious function.
Human Genome is ‘over-inflated’
What is gene?
Not only the coding sequence, a bit more …
- the entire nucleic acid sequence that is necessary for the synthesis
of a functional gene product, polypeptide or RNA, both the coding and
control sequences
5’ cap – 7-methylguanilate attached to mRNA
3’ Poly(A) site – allows cleavage by endonuclease and attachment of a poly(A) string
(100-250 bases) by Poly(A) polymerase
Cap site = region coding
for “5’-cap structure”
making ribosome-binding
site, close to the starting
AUG codon
Poly(A) site – signals 3’
polyadenilation of mRNA
Splice sites
What mutations can do?
Control regions, shared
exons or alternate parts
can be hit. Mutations d
and e will complement
each other, despite being
in the same gene.
Mutation c in the common
exon will not complement
any of the mutations.
Density of coding regions varies in different species
Genes can be SOLITARY (occur once
per haploid genome)
or form FAMILIES of DUPLICATED
genes
How does exon or gene duplication occur?
L1 – homologous noncoding regions
interspersed throughout
the genome
Duplication then can be followed by a sequence drift; divergence is driven by
beneficial mutations resulting in functional refinement, as in b-globins (Ag and Gg
genes code for embryonic versions having higher affinity to O2)
Clusters of genes: transcription factors, kinases, GPCRs, immunoglobulins, …
Duplication also generates pseudo genes (non-functional sequences resembling genes)
L1 – homologous noncoding regions
interspersed throughout
the genome
Up to 250 RNA polymerase
complexes can be transcribing
one gene simultaneously
Tandemly repeated genes
encode rRNAs, tRNAs and
histones, the components
utilized by cells in huge
quantities
Human Genome is ‘over-inflated’
Repetitious DNA
Chromosome 16 stained by a
fluorescent probe in-situ hybridized
with a simple sequence locus
Simple-sequence (satellite) DNA is typically represented by 14-500 bp
repeats in tandems of 20-100 kb. Often occurs near centromeres or in
telomeres.
Microsatellite: 1-13 bp repeats (usually 1-4), tandems are less than 150 bp
(sometimes occur within transcription units, causing diseases)
Microsatellite is thought to have originated from back-slippage of the
daughter strand on its template strand during DNA replication
Simple sequence DNA is
localized near telomeres in
mouse chromosomes
What’s the use of variable repeats? DNA fingerprinting
Minisatellite: 15-100 bp repeats making 20-50 repeat units (1-5 kb regions)
These regions are used in DNA fingerprinting
Why does the length of minisatellite repeats vary?
Southern blot of DNA taken from three
individuals, cut with a restriction enzyme and
hybridized with three different minisatellites
as probes
Mobile DNA = Transposable elements
Present in both eukaryotes and prokaryotes
Considered to be endosymbiotic, selfish DNA, with no specific
function for the host
When transposition/duplication occurs in the germ line, it is
inherited
In somatic sells transposition may inactivate a tumor-suppressor
gene causing cancer.
Interspersed repeats (moderately repeated DNA) make up 45%
of entire human DNA!
Transposons were discovered in maze by Barbara McClintock in the 1940s.
Two types of transposons
Bacterial DNA transposons = IS elements (insertion sequences)
About 20 different IS elements in E. coli
Transposition is a rare event ~10-5 to 10-7/generation, the rate is finely
tuned by evolution
One or two enzymes are coded (Transposase)
IS elements can insert into plasmids or lysogenic phages and thus can be
transferred to other cells