lecture 10 genes, genomes and chromosomes repeated and transposable elements
DESCRIPTION
Lecture 10 Genes, genomes and chromosomes Repeated and transposable elements. 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. - PowerPoint PPT PresentationTRANSCRIPT
Lecture 10
Genes, genomes and chromosomes
Repeated and transposable elements
t
i
ii ppk
S
1
ln
1 2 3 4 5 1 2 3 4 5 1 2 3 4 5
S = maxS = min
n
lattice position
Show this!
WkS ln
p – probabilities of states
What if microstates are occupied unequally? How to write the entropy?
E. coli 4.5 Mb 1 circular chromosomeS. cerevisiae 16 Mb 16 (haploid set)C. elegans 100 Mb 6A. thaliana 125 Mb 5D. melanogaster 180 Mb 4M. musculus 3200 Mb 20H. sapiens 3300 Mb 23
Caryotype of H. sapiens
Chapter 6
Chromosomal organization
Genomes of many organisms contain large amount of ‘nonfunctional’ DNA
E. coli 4.5 Mb 1Yeast 12 Mbases/haploid set 16 chromosomesFruit fly 180 4Chicken 1300 39Human 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.
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?
Clusters of genes: transcription factors, kinases, GPCRs, immunoglobulins, …
Duplication also generates pseudo genes (non-functional sequences resembling genes)
Duplication then can be followed by a sequence drift; divergence is driven by beneficial mutations resulting in functional refinement, as in -globins (A and G genes code for embryonic versions having higher affinity to O2)
L1 – homologous non-coding regions interspersed throughout the genome
L1 – homologous non-coding regions interspersed throughout the genome
Tandemly repeated genes encode rRNAs, tRNAs and histones, the components utilized by cells in huge quantities
Up to 250 RNA polymerase complexes can be transcribing one gene simultaneously
Human Genome is ‘over-inflated’
Repetitious DNA
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
Chromosome 16 stained by a fluorescent probe in-situ hybridized with a simple sequence locus
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
Southern blot of DNA taken from three individuals, cut with a restriction enzyme and hybridized with three different minisatellites as probes
Why does the length of minisatellite repeats vary?
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