1. Genome Structure and Evolution
Genes and Evolution
Genome Structure and Evolution
The C-value paradox- differences in genome size
Types of DNA- genes, pseudogenes and repetitive DNA
Gene duplication- The importance of pseudogenes in evolution and diversity
Changes in chromosome number- polyploidy, chromosome abnormalities
Chromosomal rearrangements- Inversions and translocations

2. There are different classes of eukaryotic DNA based on sequence complexity.
Which ones?

3. Reassociation Kinetics

4. 3 Main Components in Eukaryotic Genomes

6. The C-value paradox
Among multicellular eukaryotes, the size of the genome varies enormously, and cannot be explained by differences in the number of functional genes
Units of Genome size
C-vaule is the weight of the genome (in pg)
Length is measured in base pairs
kilobase (kb) = 1,000 base pairs =
megabase (Mb) = 1,000,000 base pairs = 106
gigabase (Gb) = 1,000,000,000 =

7. The C-value paradox Species Common Genome size name in bp
 phage x 104
Escherichia coli x 106
Saccharomyces cerevisiae Yeast x 107
Caenorhabditis elegans A nematode x 107
Drosophila melanogaster Fruit fly x 108
Homo sapiens Human x 109
Amphiuma species Salamander x 1010
Arabidopsis thalina Thale cress x 108
Oryza sativa Rice x 108
Hordeum vulgare Barley x 109
Triticum aestivum BreadWheat x 1010

8. Explaining the C-paradox
1- genomes differ in the amount of repetitive DNA
2- some species have more than 2 copies of each chromosome
Polyploidy
- errors in meiosis
- can be triggered by Cochicine
- Polyploids can not mate with diploids
- Polyploids can become diploid by chromosome fusion
(diploidization)

9. Types of DNA in a genome
Single or Low-Copy sequences -genes including promoters, exons and introns
pseudogenes
Repetitive DNA (middle-repetitive and highly repetitive sequences)
Multiple copy genes
Telomeres- (CCCTAAA - repeated many times)
Simple sequence repeats or SSRs - short sequences of 1- 5 bp, repeated Microsatellites Centromers, Heterochromatin
Mobile elements
transposons and retrotransposons
Telomeres
Centromere

10. Multiple copy genes
A few genes are present in multiple copies, principally because the cell needs a lot of the gene-product
e.g.
Ribosomal RNA genes are arranged in large clusters, and organisms have many copies of each (200 in humans)
Histone genes have multiple copies

11. Simple Sequence Repeats
(microsatellite DNA)
Short sequences (1-5 bases), sometimes in tandem, repeated many times and often widely distributed over the genome.
Eg. (AT)n, (GAT)n, (CTACTA)n
25% of the DNA of one crab species is AT repeats.
In replication, the number of repeats is not well copied because of slippage
Heterochromatin (regions of the chromosome that condense early in prophase) are mostly microsatellites.
Centromeres generally contain large tracts of microsatellites.

12. Mobile DNA Moves within genomes
Most of the moderately repeated DNA sequences found throughout higher eukaryotic genomes
L1 LINE is ~5% of human DNA (~50,000 copies)
Alu is ~5% of human DNA (>500,000 copies)
Some encode enzymes that catalyze movement

13. Transposon derived repeats
Long interspersed elements – LINEs
Short interspersed elements - SINEs
LTR (long terminal repeat) retrotransposons
DNA transposons
45% or more of genome

14. 4 million tranposable elements

15. DNA transposons Terminal inverted repeats Transposase 7 major classes
Transposition doesn’t occur in humans anymore
Horizontal transfer

16. Transposons The Ac transposable element of maize Inverted repeat
11-bp inverted
repeats
Exons of
transposase gene
Introns
Inverted repeat
CCAGGTGTACAAGT …………….ACTTGTACACCTGG
GGTCCACATGTTCA …………….TGAACATGTGGACC
A transposon can move at random throughout a plant genome. It is cut out of its site and reinserted into another site by the action of a transposase which it itself encodes.

17. Mechanisms of duplication
Transposons
Donor element
Target
Excision (cut)
Integration (paste)
DNA repair or

18. LTR (long terminal repeat)
Flank viral retrotransposons and retroviruses
Repeats contain genes necessary for movement and replication
Retroviruses have acquired a coat protein gene
Many fossils

19. Retrotransposons The copia retrotransposable element of Drosophila
Coding sequence (5kb) with transposase, reverse transcriptase and RNase genes
17 base
inverted repeats
Direct repeats of 267 bases
1 Single stranded RNA copy is made
2 Single stranded DNA copy is made using reverse transcriptase
3 The RNA copy is removed using the RNase
4 The DNA is made double stranded
5 The double stranded DNA is inserted using the transposase

20. LTR retrotransposons Donor element Target Transcription RNA
2nd strand synthesis
Reverse transcription
Integration (paste)

21. LINEs LINE1 – active Line2 – inactive Line 3 – inactive
Many truncated inactive sequences

23. LINEs (non-LTR retrotransposons)
Donor element
Target
Transcription
Cleavage/insertion/reverse
transcription
RNA
Integration (paste)

24. Exception – Alu elements
Derived from signal recognition particle 7SL
Does not share its 3’ end with a LINE
Only active SINE in the human genome

25. Different regions of the genome differ in density of repeats
Most LINEs accumulate in AT rich regions
Alu elements accumulate in GC rich regions

26. Mouse: blue
Human: red

28. CpG islands CpG is subject to methylation (and deamination).
Most eukaryotes show less of this dinucleotide than base composition would indicate.
Defined as regions of DNA of at least 200 bp in length that have a G+C content above 50% and above average CpG content.
Used to help predict gene sequences, especially promoter regions.
in human genome

29. CpG -> CmpG -> TpG

31. Gene Duplication
Gene duplication occurs by two quite different processes
One is duplication of large parts or whole chromosomes or even the whole genome (this last process is polyploidy)
The other is the duplication of short sections of sequence presumably due to mistakes in recombination. Unequal crossing over
A B
A B C C
A B C
Chiasma
in meiosis
Gametes

32. Gene Duplication Gene duplication leads to multiple copies of genes
Some of these are free to mutate
Mutation will normally lead to loss of function- to pseudogenes
Rarely, mutations in duplicate genes or pseudogenes produces novel, useful, products. These are new genes
Accumulated gene duplications leads to gene clusters

33. Gene duplication and evolution
The globin gene family
The human globin gene family. 15 genes, two gene clusters  
2
1 2 1 1
2  G A
1  
Myoglobin
Chromosome 16
Chromosome 11
Chromosome 22

34. A phylogeny of the globins based on sequence data
Myoglobin
Alpha chains
Zeta chains
Epsilon chains
Gamma chains
Delta chains
Beta chains
257 81 76
120 49 27 6 32
178 9
Numbers indicate the estimated
number of DNA sequence changes
along the given branch of a tree 36 11
Date of divergence
(mya)
450
370
500
210
150 50

35. Changes in Chromosome Numbers
Polyploidy- more than 2 copies of the haploid chromosomes
Dosage effect
The more copies of genes there are, the greater the dosage
Balanced changes in gene dosage are generally OK. Unbalanced are not.

36. Polyploidy is important in plant evolution
Chrysanthemum species illustrate the phenomenon
Monoploid number (the basic set) = 9 chromosomes
In Chrysanthemum species, the number of chromosomes found fall into 5 categories.
18 chromosomes = diploid (2 copies of the monoploid)
36 chromosomes = tetrapoid (4 copies of the monoploid)
54 chromosomes = hexapoid (6 copies of the monoploid)
72 chromosomes = octaploid (8 copies of the monploid)
90 chromosomes = decaploid (10 copies of the monoploid)
50% of flowering plants are polyploid

37. Chromosomal Rearrangements
Inversions
a b c d e f g
Double break in chromosome
a b c d e f g
Repair inverts the inner section
a b e d c f g

38. Chromosomal Rearrangements
Translocations
t(8; 14) translocation in Burkitt's lymphoma deregulates immunoglobulin
t(4; 11) of acute childhood leukaemia resulting in an formation of ALL1 oncogene

39. Mouse-human synteni
342 segments

41. Fig. 1. Arrangement of duplicated protein-encoding genes in Oryza
Paterson, A. H. et al. (2004) Proc. Natl. Acad. Sci. USA 101,
Copyright ©2004 by the National Academy of Sciences

42. Fig. 3. An early phylogenetic tree of genomic duplications for the angiosperms
Paterson, A. H. et al. (2004) Proc. Natl. Acad. Sci. USA 101,
Copyright ©2004 by the National Academy of Sciences