1. Gene & Genome Evolution
Chapter 9
You will not be responsible for:
Read the How We Know section on Counting Genes, and be able to discuss methodologies for doing so.
Questions in this chapter you should be able to answer:
Chapter 9- #1 -7 , 9, , 18
Gene & Genome Evolution

2. Gene & Genome Evolution
Trends in genome evolution
1) Genome expansion
2) Accumulation of
Repetitive DNA
3) Accumulation of
transposable elements
4) Intron Expansion
5) Loss of GC pairs
6) Accumulation of SNPs
Figures 9-32 & 9-33
Gene & Genome Evolution

3. Gene & Genome Evolution
Sizes of genomes
Base pairs # Genes
Viruses
Hepatitis-B 3,200 4
HIV 9,700 9
Influenza 13,
Ebola 19,000 7
Epstein-Barr virus 172,282 80
Bacteria
Mycoplasma genitalium 580,
Treponema pallidum 1,138,011 1,039
E. coli 5,440,000 5,416
Single celled eukaryotes
Yeast 12,495,682 5,770
Chlamydomonas 111,000,000 17,700
Insect
Fruit fly 122,653,977 15,000
Plants
Soybean 950,000,000 46,430
Norway Spruce 196,000,000 28,354
Corn 5,000,000,000 39,000
Animals
Mouse 2,800,000,000 23,000
Humans 3,300,000,000 21,000
Gene & Genome Evolution

4. Gene & Genome Evolution
~50% of the human genome is repetitive DNA
Two main types:
“Tandem repetitive DNA”:
base sequences
“CAG CAG CAG CAG CAG…
“GGAAT GGAAT GGAAT…
“Interspersed Nuclear Elements”:
100s – 104 base sequences
-- most are “transposable elements”
-- make copies of themselves
. . . repeated 10s  106s of times
Gene & Genome Evolution

5. Gene & Genome Evolution
Tandem Repetitive DNA is linked to several genetic diseases
-- “Trinucleotide repeat expansion” disorders
Huntington’s disease
-- neurodegenerative
-- late onset
-- inheritance is Dominant
-- Repeat #  onset age & severity
Gene & Genome Evolution

6. Transposable Elements have accumulated over time
SINE (short) elements, e.g, ‘Alu’
– 300 Bp long
copies = ~ 13% of genome
LINE (Long) elements, e.g., ‘L1’
s Bp long
~ 500,000 copies = ~20% of genome
-- encode genes for own movement
Examples
Tick and Sick - 7

7. Transposable Elements are fascinating -- and disconcerting!
DNA that moves around
“Jumping genes”
Some move via “Cut and Paste” (no longer active in humans)
Some move via “Copy and Paste” -- still active!!
Tick and Sick - 7

8. Gene & Genome Evolution
How do transposable elements move?
1) DNA-only mechanism -- common in bacteria, plants, yeast, insects
Inverted sequences
Mechanism of cut and paste transposition
2) Alu and Li are retrotransposons
-- Pass through RNA form
-- Use reverse transcriptase
06_33_transposons.jpg
Gene & Genome Evolution

9. TE movements have been linked to human diseases
-- estimated to cause 0.3% of human genetic disorders
Belancio et al (2008) Genome Res. 18:
Genetic analysis of mutated genes in individuals
BRCA1 gene: 42% of gene is Alu sequences in introns
Tick and Sick - 7

10. The Good News: TEs are not running rampant
Most are inactive
– mutated ‘fossils’
– host suppressive mechanisms
~ active L1s
Beneficial roles
-- not fully understood
Roles in regulating gene expression
-- the space between genes matters
-- changes alter patterns of gene expression
-- TE RNAs appear to have functions
Have given rise to new genes
--e.g., telomerase; RAG enzymes
-- Intron/Exon diversity
Roles in neurological development?
Tick and Sick - 7

11. Gene & Genome Evolution
How do genes evolve over time?
Mutation of coding regions
Mutation of regulatory regions
Chromosome/Gene/Exon duplications
Exon/intron shuffling & Transposition
Horizontal gene transfer
Gene & Genome Evolution

12. Gene & Genome Evolution
How do new genes evolve?
Exon duplication & shuffling is common
Gene & domain duplications occurred during evolution of the “Ig-Superfamily”
Exon shuffling &
duplication has
occurred during
evolution of
these genes
Gene & Genome Evolution

13. Gene & Genome Evolution
Gene duplications are common
Divergence of function
e.g. Fetal/human hemoglobin
Families of related genes
Pseudogenes can result
Gene & Genome Evolution

14. Gene & Genome Evolution
Horizontal Gene Transfer
-- can move blocks of genes
Asexual transfer of genes between organisms
Most common in single-celled organisms
-- why?
Bacterial genetic recombination
-- spread of Ab resistance
Gene & Genome Evolution

15. Gene & Genome Evolution
Simple mutations to regulatory genes can cause dramatic changes in development
Explains “Punctuated Equilibrium”
Mutations to “master regulatory gene”
Antennapedia (antp)
-- antennae transformed to legs
bithorax (bx) + postbithorax (pbx)
-- extra set of wings
Gene & Genome Evolution

16. Gene & Genome Evolution
Loss of GC pairs in Vertebrates ‘
Cytosine methylation
and gene regulation
CpG’ vs ‘GC’ bp
Methylation of CpG
leads to
loss of GC bp’s
Deamination of methyl-C yields T – G mismatch
Gene & Genome Evolution

17. Gene & Genome Evolution
Creation of CpG islands
CpG remains in ‘islands’
Where found?
housekeeping genes
non-coding regions
Frequencies
Group GC CpG
Fish & amphibians 44% 1.8%
Birds and mammals 42% %
“GC-islands” 4-6%
Jabbari, et al Gene 205:
Gene & Genome Evolution

18. Gene & Genome Evolution
Introns have gotten bigger
Genome sizes
Puffer fish: 400,000,000
Human: 3,000,000,000
Huntingtin gene
– mutations cause Huntington’s Disease
Gene size
Puffer fish: 22,000 bases
Human: ,000 bases
Both produce proteins of
~ 3000 AAs!!!
All expansion is in Introns!
Every exon and
intron align exactly
Gene & Genome Evolution

19. Gene & Genome Evolution
4) Intron expansion
Genome sizes
Puffer fish: 4 x 108
Human: 3 x 109
Huntingtin gene size
Puffer fish: 2.4 x 104
Human: 1.8 x 105
All 67 exons align!!
Expansion and mobile elements occur in introns
Gene & Genome Evolution

20. Gene & Genome Evolution
Accumulation of single-nucleotide polymorphisms (SNP)
distinguish individual genomes
Consequence of “point mutations”
107+ documented in humans
Can influence:
Our individual physical traits
Disease susceptibility
Risk factors for disorders
e.g., Macular Degeneration
SNP in Complement factor H
His  Tyr
5 – 7x >risk
Gene & Genome Evolution

21. Gene & Genome Evolution
What is a “silent mutation”?
And why are they
not always silent?
Sometimes:
Wobble position
Non-coding regions
Sometimes not:
regulatory sites
chromosome
codon usage
Arginine tRNA occurrence
Codon tRNA [tRNA]1
CGU arg
CGC arg2
CGG arg
AGA arg
AGG arg
1tRNA abundance in E. coli:
Burg & Kurland (1997) J. Mol. Biol. 270: 544
2Frequency in E. coli O127:H6
What would be the expected effect on translation rate of …
… CGU CGC mutation?
… CGU CGG mutation?
Gene & Genome Evolution