BIOB 272 1st Edition Lecture 17Outline of Last Lecture Population GeneticsI. Causes of Changes in Genealogy1. Reversals (back mutations)2. Parallel SubstitutionsII. Phylogenetics in Practice- HomoplasyIII. Darwin’s Four Motivation Sources1. Evidence for descent with modification2. Geology and Uniformitarianism3. Artificial Selection4. Struggle for existence within poplutionsIV. Darwin’s Four Postulates for Evolution by Natural Selection1. Individuals vary2. At least some variation is heritable3. Some individuals leave more progeny than others4. Variation among individuals in survival, reproduction not random, but depend onheritable trait variationV. The Equilibrium Population- Hardy Weinberg Equilibrium ModelVI. Testing for Hardy-Weinberg ProportionsVII. Occurrence of Cystic Fibrosis: Autosomal Recessive (cc)These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.Outline of Current Lecture Population Genetics (drift)I. Relaxing the assumptions of Hardy-Weinberg Equilibrium ModelII. Mutationa. Important Termsi. Mutationsii. Polymorphismsiii. Genetic drifiv. Substitutionb. Molecular Basis of Mutationsc. Point MutationsIII. Single Nucleotide Mutations in Genesa. Nonsense Mutationb. Missense Mutationi. Transitionalii. Transversionalc. Frameshif Mutationsd. Synonymous (Silent) MutationsIV. Appearance of Most MutationsV. Amounts of Mutations/ Mutation RatesVI. How Do Mutations Affect Hardy-Weinberg Equilibrium?VII. How to Measure Mutation Ratesa. Indirect b. DirectVIII. Mutations in Eggs vs. SpermIX. Mutation SummaryCurrent LecturePopulation Genetics (drift)I. Relaxing the assumptions of Hardy-Weinberg Equilibrium Model1. Random mating2. No mutation3. Large (infinite) population size (no genetic drif)4. No differential survival or reproduction (no natural selection)5. No migration (no gene flow)*If population not in H-W eq then we may be looking at population genetic evidence that one ormore of these are at work.-use HW equilibrium as null hypothesisII. Mutationa. Important Terms- Mutations: change in genetic information-our focus=change in the DNA sequence of genes- Forces that Shape Variation:1. Genetic Drif2.Natural Selection3. Gene flow (migration)4. Population Structure- Changesin DNA that arise in an INDIVIDUAL- Only Mutations in Germ Cells are heritable- Polymorphisms: when a mutation is present in one or more individuals in a population- Genetic drif: what causes most mutations (Monday)- Substitution: when a mutation becomes fixed in a population or speciesb. Molecular Basis of MutationsType of Mutation MechanismPoint Mutation DNA ReplicationDNA DamageSmall insertion or deletion (INDEL) -Unequal crossing over misalignment during DNA rep. -Insertion of mobile elementLarge Deletion, translocation or inversionUnequal crossing over DNA damageLoss of a whole chromosome Segregation at mitosis/meiosisc. Point Mutations: Changes to a single nucleotide- Any of these can give rise to SNPs : Single Nucleotide Polymorphisms- DNA replicated during mitosis and meiosis= opportunity for error and repairo When repaired, mismatches can occur (between purines and pyrimidines):- If C=T, a mutation- If A=G, no mutationIII. Single Nucleotide Mutations in Genesa. Nonsense Mutation: abnormally short (truncated) proteinb. Missense Mutation: Slight change in overall protein- Substitute single base pair- Might be deleterious- Can have positive effects- Transitional- Transversionalc. Frameshif Mutations: insertion= shifs everything downstream and new stop codons arise= RADICALLY change sequence- In lots of human diseases- Can be deleterious (bad)d. Synonymous (Silent) Mutations: tend to occur at 3rd position- NOT always thoughIV. Appearance of Most Mutationsa. Most appear to be neautral (silent or have no effect on fitness because:- They occur in noncoding regions of the genome (98% genome- introns, intergenic regions, etc)- They occur in genes but do not change protein (genetic code is degenerate- They change protein sequence but do not affect the phenotype of fitness** Most non-silent mutations tend to be deleterious (bad)V. Amounts of Mutations/ Mutation Rates- Estimates vary =about 2x10^-5 (1/50000) harful mutations per gene pergeneration is conservative- Given about 22,000 genes per human genome, every gamete has about a 50% chance of carrying a harmful mutation in some gene- Because we are 2N= all of us likely carry at least 1 new harmful mutation (ofen recessive)VI. How Do Mutations Affect Hardy-Weinberg Equilibrium?- Very Subtle= less than 1x10-5 of mutation rates (u)- Mutation rates are low per site per generation (2.5x10^8)- Mutations are common per diploid genome per generation= about 175VII. How to Measure Mutation Ratesa. Indirect 1. Frequency of Mendelian diseases (mutation-selection balance)2. Evolutionary comparisons (divergence between homologous sequences)b. Direct1. Frequency of children with dominant diseases born to unaffected parents2. Direct observation in large experiments with many progeny3. Genome sequencing of multiple generations (family pedigree)VIII. Mutations in Eggs vs. Sperm:- Much higher mutation rate in sperm (more crossing over in meiosis/ mitosis of sperm) so higher mutation rate in sperm than eggsIX. Mutation Summary:- Mutation common on a per gamete (or per genome)basis, but rare per gene- Most mutations in Eukaryotes neutral or nearly so- Majority mutations with phenotypic effects aredeleterious (bad) and recessive (hidden)- Mutation alone has little effect on HW equilibrium, butprovides ultimate raw material for evolution- • Mutation rates may be affected by sex, and other-