Genes, genomes and chromosomes

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Lecture 10 Genes, genomes and chromosomes
Repeated and transposable elements
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What if microstates are occupied unequally? How
to write the entropy?
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p probabilities of states
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lattice position
S max
S min
Show this!
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E. coli 4.5 Mb 1 circular chromosome S.
cerevisiae 16 Mb 16 (haploid set) C. elegans 100
Mb 6 A. thaliana 125 Mb 5 D. melanogaster 180
Mb 4 M. musculus 3200 Mb 20 H. sapiens 3300
Mb 23
Chapter 6
Caryotype of H. sapiens
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Chromosomal organization
Genomes of many organisms contain large amount of
nonfunctional DNA E. coli 4.5
Mb 1 Yeast 12 Mbases/haploid set 16
chromosomes Fruit fly 180 4 Chicken 1300 39
Human 3300 23
Tulips 30000 Mbases Amoeba 660,000
Mbases/nucleus 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.
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Human Genome is over-inflated
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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
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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.
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Density of coding regions varies in different
species
Genes can be SOLITARY (occur once per haploid
genome) or form FAMILIES of DUPLICATED genes
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How does exon or gene duplication occur?
L1 homologous non-coding 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)
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L1 homologous non-coding regions interspersed
throughout the genome
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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
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Human Genome is over-inflated
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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
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Simple sequence DNA is localized near telomeres
in mouse chromosomes
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Whats the use of variable repeats? DNA
fingerprinting
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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
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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/duplicat
ion 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.
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Two types of transposons
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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
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