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CHANGES IN THE
GENOME
• MUTATIONS
• A) chromosomal changes
• B) DNA seq. changes
Note: Mutation rate in
transcription much higher than
during replication…why?
• New source of alleles
 variety
• Double-edged sword!
• Can be used to trace
evolutionary history
CHROMOSOMAL
MUTATIONS
• ANEUPLOIDY –
MISSING/EXTRA CHROM.
• POLYPLOIDY – EXTRA
SETS
ie. P. Kewensis 2N = 36
from hybridization (2N = 18)
Translocation –
relocation of groups of
base pairs from one part
of the genome to another
(usually bet. 2 nonhomologous
chromosomes…can lead
to leukemia)
DNA MUTATIONS
Autosomal Condition
Huntington’s – chromosome 4
Normal allele  6-35 CAG repeats
Huntington’s  40-150+ CAG
repeats
Causes Neurodegeneration
Blocks acetyl-transferases in
brain cells (reg. gene expression)
• X-linked
• Fragile X syndrome
• CGG repeats 200-1000
times
vs 50X for norm
Leads to mental retardation
(abnormal nerve cell
dendrites)
DNA MUTATIONS
• SILENT – same amino
acid
• MISSENSE – diff’t a.a.
• NONSENSE – stop codon
• FRAMESHIFTING
Missense
Sickle cell anemia 
Base pair sub GAG (Glu)
changed to GTG (Val)
… Or
Nonsense  lethal (base
pair sub)
RAS mutation
•
th
12
codon in DNA
GGC  gen Gly
th
Mutant 12 codon
GTC  gen Val
Affects RAS’s ability to
hydrolzye GTP to GDP...Sig?
– Deletion – removal of
1 or more bp (leads to
frameshifting …very
serious)
– Insertion – addition of
1 or more bp (see
above)
Transposons-Barbara McClintock
• Are moveable genetic elements.
• DNA sequence can jump into a gene
rendering it inactive
• Contain enzyme transposase.
• Most are retrotransposons (use
reverse transcriptase to conv.
mRNA to DNA for incorporation into
the gene)
• Ie 800 bp insertion in starch-related
enzyme in peas  “wrinkling”
PSEUDOGENES
• “false” or “dead genes”
• Produced 2 ways:
a) during division an extra
copy is inserted into
genome in a new location
b) reverse transcription
Reverse transcription
• Retrotransposition is the
insertion of DNA into Genome
• Carried out by LINES (long
interspersed nuclear elements)
that sweep up DNA and mRNA
(then retrotransposed) for
insertion into genome
RPL21
• Ribosome Protein
family = 80 genes
• RPL21 140
pseudogenes
• Genes become
pseudogenes if they
incur:
a)Loss of promoter
b)Loss of introns
c)Mutations in the gene
(deletions, insertions,
non-sense)
Lineages diverged 75 mya
Mouse 14 / Human 8
GULO Pseudogene
• Functional in rodents
• Nonfunctional in primates
• GULO makes an enzyme in
the pathway for making
vitamin C
• Explains why we need vit-C
EVOLUTIONARY IMPORTANCE
• Useful molecular clocks as they
are not constrained by selection –
99% human/rat gene sim vs few%
in pseudogene sim
• Shows primate lineage lost many
olfactory genes (300 human
pseudogenes still functional in
rats) – tradeoff with better vision!
FOUNDER MUTATIONS
• Mutation arises in the founder
and is passed on
• Can be classified as a founder
by examining surrounding
sequences…if the same it’s a
founder mutation / if not it’s a
Hot-Spot mutation
Normal, Founder, Hotspot
Sickle Cell – Founder
Achondroplasia – Hot Spot
Value of Founder….
• Can be dated by examining DNA
surrounding founder mutation (the
Haplotyope)
• Haplotyopes get shorter with time
(crossing over) and can be used
as a clock and to determine
ancestral lineages
Founder Mutations
• Persist because they offer
advantages as heterozygotes
• Ie Cystic Fibrosis (CFTR gene)
 prot. from diarrhea
• Sickle Cell (HbS gene)  prot.
from Malaria
MUTATIONS AND
EVOLUTION
• MUTATIONS CAN….
1.Occur in non-coding reg.
2. Be silent in coding region
3. Be shielded (diploid)
4. Affect gene (pos/neg)
MC1R MUTANTS
• Mutants in MC1R gene
• 1 in 25 million chance of
generating black
coloration
• A population of 100,000
mice will generate 1
black form every 100
years
• ROCK POCKET MICE
 lava flows vs sandy
areas
DUPLICATIONS
• EXPANSION OF GENETIC
INFORMATION ie Globin
Family; ADH vs OXYTOCIN
• ALLOWS FOR FINETUNING OF 1 GENE
without “harm” to other
OPSIN DUPLICATIONS
• LAMPREY 5
• BIRDS, REPTILES,FISH 4
• MAMMALS 2 (blue,
yellow)
• OLD WORLD MONKEYS,
APES , HUMANS - 3
• MAMMALS  LOSS OF
OPSINS DURING THE
DINOSAUR ERA
• MAMMALS WERE
NOCUTURNAL
• TRICHROMATIC
• RED, GREEN, BLUE
• RED/GREEN – X chrom
 RED OPSIN (560 nm)
 GREEN OPSIN (530
nm)
• RED/GREEN  98%
similar; same chromosome
• 15 amino-acid diff; 3
account for most of 30 nm
difference