1. Lecture 10 Genes, genomes and chromosomes
Repeated and transposable elements

2. p – probabilities of states
What if microstates are occupied unequally? How to write the entropy? n
p – probabilities of states 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5
lattice position
S = min
S = max
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3. Chapter 6 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

4. 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
Chicken
Human
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.

6. Human Genome is ‘over-inflated’

7. 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 ( bases) by Poly(A) polymerase

8. 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.

9. Density of coding regions varies in different species
Genes can be SOLITARY (occur once per haploid genome)
or form FAMILIES of DUPLICATED genes

10. 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)

11. L1 – homologous non-coding regions interspersed throughout the genome

13. 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

14. Human Genome is ‘over-inflated’

15. 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 bp repeats in tandems of 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

16. Simple sequence DNA is localized near telomeres in mouse chromosomes

18. What’s the use of variable repeats? DNA fingerprinting

19. These regions are used in DNA fingerprinting
Minisatellite: bp repeats making 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

20. 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.

21. Two types of transposons

22. 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