1. Organization of the human genome
Genome structure
Nuclear vs. mitochondrial genomes
Gene families
Transposable elements
Other repeated sequences

3. Organization of the human genome
Mitochondrial genome: Origin
Endosymbiont Hypothesis
Ancient archaeal cell engulfed a proteobacterium and eventually came to rely on the symbiont for survival.
Evidence
Circular genome
Autonomous ribosomes

4. Organization of the human genome
Mitochondrial genome
Small (16.5 kb) circular DNA
1 gene/0.45 kb
Very few repeats
No introns
93% coding
Heavy and Light strands

5. Organization of the human genome
Mitochondrial genes
rRNA, tRNA and protein encoding genes (37)
28 encoded by the heavy strand
24 RNA products and (23s, 16s, tRNAs)
13 protein coding genes

7. Organization of the human genome
Mitochondrial genes
rRNA, tRNA and protein encoding genes (37)
28 encoded by the heavy strand
24 RNA products and (23s, 16s, tRNAs)
13 protein coding genes
Genes are transcribed as two transcription units and cleaved afterwards
Genes may overlap

8. Organization of the human genome
Limited autonomy of mt genomes mt encoded nuclear
NADH dehydrog 7 subunits >41 subunits
Succinate CoQ red 0 subunits 4 subunits
Cytochrome b-c1 comp 1 subunit 10 subunits
Cytochrome C oxidase 3 subunits 10 subunits
ATP synthase complex 2 subunits 14 subunits
tRNA components 22 tRNAs none
rRNA components 2 components none
Ribosomal proteins none ~80
Other mt proteins none mtDNA pol, RNA pol etc.

10. Organization of the human genome
Special Features
Mitochondrial genetic code (reduced selection)
Two extra stop codons: AGA and AGG
UGA = tryptophan, AUA = Methionine/start
No recombination
Maternal inheritance

11. Organization of the human genome
Mitochondrial genome replication
OH – Origin of heavy strand replication
OL – Origin of light strand replication
D-loop

13. Organization of the human genome
Nuclear genome
3300 Mb
23 (XX) or 24 (XY) linear chromosomes
30-35,000 genes
1 gene/40kb
Introns
3% coding
Repetitive DNA sequences (45%)
Recombination
Mendelian inheritance (X + auto, paternal Y)

14. Organization of the human genome
Contrasting gene densities
Some regions of the genome are gene-rich and others are gene-poor
HLA high density
Dystrophin low density

16. Organization of the human genome
Gene families
Thought to be generated by gene duplication
Functionally similar genes are occasionally clustered, but usually dispersed throughout the genome

17. Histone gene distribution

18. Organization of the human genome
Genes vary in size and exon content
A general inverse relationship.

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Exon content vs. length

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22. Organization of the human genome
Genes within genes
Intron 26 of the NF1 gene contains three internal genes.

24. Organization of the human genome
Gene families:
defined by extensive DNA similarity
Alpha and Beta globin genes
defined by large highly conserved domains
defined by conserved amino acid motifs
DEAD box
WD repeats

26. Organization of the human genome
Superfamilies
Common structural features
Ig superfamily
Cell surface receptors

28. Organization of the human genome
Clustered gene families
Single clusters (sometimes tandem)
Growth hormone 5 copies (67kb)
a-globin 7 copies (50kb)
multiple clusters (sometimes tandem)
Hox genes (multi) four clusters
Olfactory receptors in 25 large clusters

30. Organization of the human genome
Interspersed gene families generated by:
Nuclear translocation
Gene/genome duplication
Pax 9 copies
Actin >20 copies
retrotransposition events
Alu elements (repeats) 1.1 million
LINE elements (L1) ,000

31. Organization of the human genome
HLA heavy chain gene cluster: an example
Gene fragments
Pseudogenes
Truncated genes

33. Organization of the human genome
Processed pseudogenes
Originate by reverse transcription of a processed transcript
TPRT

35. Organization of the human genome
Repetitive DNA
Micro and minisatellites
Retrotransposons (LINEs and SINEs)
Chromosomal location of repeats
Telomeres
Centromeres

37. Organization of the human genome
Formation of higher order repeat units

39. Organization of the human genome
Human transposable elements

41. Organization of the human genome
Transposable elements with RNA intermediates
Endogenous retroviruses
Retrotransposons
Retropseudogenes

42. SINE Mobilization – “Copy and Paste”
Reverse transcription and insertion
Pol III transcription
1. Usually a single ‘master’ copy
2. Pol III transcription to an RNA intermediate
3. Target primed reverse transcription (TPRT) – enzymatic machinery provided by LINEs

44. Organization of the human genome
Human transposable elements
Alu elements
LINE elements

46. Organization of the human genome
Mobile elements and gene structure
RB1 region
Alu
LINE
Simple sequence repeats