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 generatinggenetic variation?

• How do biologist measure genetic variationin 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) orpyrimidine for pyrimidine (T or C)

• Transversion: purine for pyrimidine orpyrimidine for purine

• Transition:Transversion 2:1

Synonymous and Non-synonymous 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 littleeffect, not easily detected

• Easiest data to get are from appearance ofnon-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 ratesMutations 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 aspecies

• 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 onchromosome 2

• In D. teissieri and D. yakuba a similar genealso found on chromosome 3

• Both apparently functional

• The one on chromosome 3 may have arisenby insertion of reverse transcribed mRNA !

Chromosome alterations

• Inversions

• Polyploidy

Inversion

Inversions and linkage

• Linkage: non-independent assortment atmeiosis

• Inversion prevents alignment

• Crossing over (recombination) very rarewithin an inversion– Genes within an inversion are linked

– Inherited together as a unit

Advantage of inversion

• alleles that function well together staytogether– Not broken up by recombination

• If a linkage group is particularly adapted toan ecological circumstance, then individualswith linked genes may outreproduceindividuals with unlinked genes– Inverted linkage group increases in frequency

Drosophila subobscura

• Has 6 chromosomes, each of which ispolymorphic for inverted linkage groups

• Frequency varies geographically withclimate: called a cline

• Semi-natural experiment: fly accidentallyintroduced 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

• What is ploidy?

• Haploid

• Diploid

• So what could polyploid be?

• Common in plants, rare in animals– Self fertilization increases likelihood

Tetraploidy

• Meiosis errorproduces diploidgametes

• With selffertilization, 4nindividual results

Polyploidy and speciation

• 4n (or 8n or whatever) individual notcompatible 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 as2 for each 10,000 offspring!

Measuring genetic variation

• Classical view: there should be little geneticvariation– 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 revealsgenotype

• E.g. human resistance to parasitic flatwormSchistosoma mansoni– Brazil 60% homozygous resistant; 5%

homozygous susceptible; 35% heterozygous

Electrophoresis

Observinggenetic variation

Recall the delta 32 mutation?

• That was the 32 base pair deletion in theCCR5 co-receptor

• HIV binds to the CD4 receptor and normalCCR5 co-receptor, gets into cell

• Delta 32 mutation stops HIV from bindingand getting into the cell

CCR5 Delta32 geneticvariation

PCR increases quantity ofDNA

Restriction enzyme cuts of332 bp chunk

Remainder is one of twotypes:

403 bp wild type

371 bp delta 32

Allele frequency

• Delta 32 allele of CCR5 prevents HIVinfection

• We’d like to know how frequent that alleleis

• We’d also like to know how the variation isdistributed

Delta 32genotypes in

differentpopulations

Calculating allele frequency fromgenotypic data

• +/+ = homozygous wild type• +/32 = heterozygous• 32/32 = homozygous recessive

• Suppose genotypic frequencies are+/+ = 25 people+/32 = 15 people32/32 = 10 people

50 people total; 100 alleles total

Geographic genetic variation

Lactate dehydrogenase in mummichog(Fundulus heteroclitus)

LDH-Bb has higher catalytic activity atcolder 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

Populationheterozygosity

Generalization

1/3 to 1/2 of enzyme lociare polymorphic

Average individualheterozygous at 5 to15% 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:– Mutation -> new alleles– Unequal crossover -> new genes– Insertion of rt transcribed mRNA -> new genes– Inversions -> linkage groups– Improper meiosis -> polyploidy

• Next 4 lectures cover ~100 pages and 2 chapters– Keep up with the reading