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 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 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

• 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: – 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