Download Mechanisms of Evolution

Mechanisms of Evolution
• Mutation and Genetic Variation
• Mendelian Population Genetics
– Selection and mutation
• Mendelian Population Genetics
– Migration, Drift, Non-random Mating
• Evolution at Multiple Loci
– Linkage, sex, and quantitative genetics
Mutation and Genetic Variation
Importance of Mutation
• Source of new genetic variation
• Without mutation
– No new genes
– No new alleles
– Eventually no evolutionary change
• Even if there is selection
Two major questions
• What are the mechanisms generating
genetic variation?
• How do biologist measure genetic variation
in populations?
Major classes of mutations
DNA recap
DNA
DNA -> mRNA -> Protein
• DNA sequence read as triplets
– Three bases encode 1 amino acid
Point Mutation
• Single base substitution
– Error in synthesis
– Error in repair after damage
• Transition: purine for purine (A and G) or
pyrimidine for pyrimidine (T or C)
• Transversion: purine for pyrimidine or
pyrimidine for purine
• Transition:Transversion 2:1
Synonymous and Nonsynonymous point mutations
• Synonym: word that says the same thing
• Codon UAU = Tyrosine
• Codon UAC = Tyrosine
• CAC = Histidine
• CAA = Glutamine
• Third position mutations often silent (synonymous)
Non-synonymous mutation
Sickle-cell
• Mutant hemoglobin crystalizes, pulling in wall
and deforming cell
• Sickled cells get stuck in capillaries
• Homozygous recessive usually die young
• Homozygous dominant susceptible to malaria
• Heterozygous individuals resistant to malaria
Mutation rates - hard to measure
• Silent mutations, or mutations with little
effect, not easily detected
• Easiest data to get are from appearance of
non-functional (knockout) mutations
– But there are a lot of ways to knock out a gene
Ways to get cystic fibrosis:
30,000 disease causing alleles
# mutants
Exons
Function
Knockout mutations
Mutation rates
Mutations in corn
• Mutation rate low on a per gene basis
• Common considering the number of genes
Mutation rates variable
• 500 times among different genes within a
species
• Potentially 100,000 times across species
• Why?
– Among individuals
– Among species
– Among genes
Variation in mutation rate
• Among individuals
– Allelic differences in DNA polymerase
• Making new errors
– Allelic differences in DNA repair
• Fixing the errors
• Among species
– Generation time likely important
• Among genes
– Likely to depend on fitness effects
New genes
• Gene duplications
– Unequal crossover
• Overprinting
• cDNA insertion
Unequal crossover
Globin genes
• Hemoglobin molecule has 4 subunits
• Adult humans
– 2 are from alpha cluster on chromosome 16
– 2 from beta cluster on chromosome 11
• Fetal humans in first trimester
– two zeta and 2 epsilon chains
– Higher oxygen affinity than adult hemoglobin
Homology of globin genes
• Exon and intron positions and length
• Structure and function
• Sequence
Other gene families
Overprinting
• mutation creating a new start codon (AUG) can
create a new gene
• Two genes share a section in common
• Tymoviruses have overprinted section
cDNA insertion
• Adh gene in Drosophila usually on
chromosome 2
• In D. teissieri and D. yakuba a similar gene
also found on chromosome 3
• Both apparently functional
• The one on chromosome 3 may have arisen
by insertion of reverse transcribed mRNA !
Chromosome alterations
• Inversions
• Polyploidy
Inversion
Inversions and linkage
• Linkage: non-independent assortment at
meiosis
• Inversion prevents alignment
• Crossing over (recombination) very rare
within an inversion
– Genes within an inversion are linked
– Inherited together as a unit
Advantage of inversion
• alleles that function well together stay
together
– Not broken up by recombination
• If a linkage group is particularly adapted to
an ecological circumstance, then individuals
with linked genes may outreproduce
individuals with unlinked genes
– Inverted linkage group increases in frequency
Drosophila subobscura
• Has 6 chromosomes, each of which is
polymorphic for inverted linkage groups
• Frequency varies geographically with
climate: called a cline
• Semi-natural experiment: fly accidentally
introduced to Chile and Washington state
Inversion frequency selected
• Genes within inversion affect body size
• Smaller flies favored in hot dry climates
• Larger flies favored in cooler wetter
climates
Polyploidy
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•
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•
What is ploidy?
Haploid
Diploid
So what could polyploid be?
• Common in plants, rare in animals
– Self fertilization increases likelihood
Tetraploidy
• Meiosis error
produces diploid
gametes
• With self
fertilization, 4n
individual results
Polyploidy and speciation
• 4n (or 8n or whatever) individual not
compatible with normal 2n
• Reproductively isolated
• Estimated that 1/2 of all flowering plant
species are polyploid
– Not all became species because of ploidy
• Polyploid formation may be as common as
2 for each 10,000 offspring!
Measuring genetic variation
• Classical view: there should be little genetic
variation
– Selection should produce the ‘best’ type
– Called wild type
– Other variants eliminated
• Data show abundant genetic variation
Phenotypic assay
• Mendel’s peas
– Red
– White
• Works ok if phenotype directly reveals
genotype
• E.g. human resistance to parasitic flatworm
Schistosoma mansoni
– Brazil 60% homozygous resistant; 5%
homozygous susceptible; 35% heterozygous
Electrophoresis
Observing
genetic variation
Recall the delta 32 mutation?
• That was the 32 base pair deletion in the
CCR5 co-receptor
• HIV binds to the CD4 receptor and normal
CCR5 co-receptor, gets into cell
• Delta 32 mutation stops HIV from binding
and getting into the cell
CCR5 Delta
32 genetic
variation
PCR increases quantity of
DNA
Restriction enzyme cuts of
332 bp chunk
Remainder is one of two
types:
403 bp wild type
371 bp delta 32
Allele frequency
• Delta 32 allele of CCR5 prevents HIV
infection
• We’d like to know how frequent that allele
is
• We’d also like to know how the variation is
distributed
Delta 32
genotypes in
different
populations
Calculating allele frequency from
genotypic data
• +/+ = homozygous wild type
• +/32 = heterozygous
• 32/32 = homozygous recessive
• Suppose genotypic frequencies are
+/+ = 25 people
+/32 = 15 people
32/32 = 10 people
50 people total; 100 alleles total
Geographic genetic variation
Lactate dehydrogenase in mummichog
(Fundulus heteroclitus)
LDH-Bb has higher catalytic activity at
colder temperatures
Lactate -> pyruvate
Average (mean) heterozygosity
• To compare across studies we need a metric
• Mean heterozygosity is either
– Average frequency of heterozygotes across loci
– Or
– Proportion of heterozygous loci in the ‘average’
individual
Population
heterozygosity
Generalization
1/3 to 1/2 of enzyme loci
are polymorphic
Average individual
heterozygous at 5 to
15% of loci
Summary
• There is gobs of genetic variation
– Measured by electrophoresis of proteins or DNA
– Summarized as heterozygosity or % polymorphic loci
• Genetic variation created by:
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–
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Mutation -> new alleles
Unequal crossover -> new genes
Insertion of rt transcribed mRNA -> new genes
Inversions -> linkage groups
Improper meiosis -> polyploidy
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