Genetics: From genes to genomes - Chapter 19: Beyond the individual gene and genome

PowerPoint to accompanyGenetics: From Genes to GenomesFourth EditionLeland H. Hartwell, Leroy Hood, Michael L. Goldberg, Ann E. Reynolds, and Lee M. SilverPrepared by Mary A. BedellUniversity of Georgia*Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th editionBeyond the Individual Gene and Genome*PART VICopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19Variation and Selection in Populations19.1 The Hardy-Weinberg Law: Predicting Genetic Variation in Populations19.2 Causes of Allele Frequency Changes19.3 Analyzing Quantitative VariationCHAPTER OUTLINECHAPTERThree subfields of genetics based on the unit object that is the focus of studyMolecular genetics – the unit entity is the geneFormal genetics – the unit entity is the individual organism, defined by genotypePopulation genetics – the unit entity is a population of interbreeding individualsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Terms used to describe populationsPopulation – group of interbreeding individuals of the same species that inhabit the same space at the same timeGene pool – sum total of alleles carried by all members of a populationChanges can occur because of mutation, immigration of new individuals into or out of the population, or decreased fitnessMicroevolution – changes in allele frequencies within a populationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Terms used to describe populations (cont)Phenotype frequency – proportion of individuals in a population that have a particular phenotypeGenotype frequency – proportion of individuals in a population that carry a particular genotypeExample: A gene with two alleles (A and B) in a population of 20 individuals 12 are AA 4 are AB 4 are BB Genotype frequencies: AA = 12/20 = 0.6 AB = 4/20 = 0.2 BB = 4/20 = 0.2 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Calculating allele frequenciesAllele frequency – proportion of gene copies in a population that are of a given allele typeExample with genotype frequencies: AA = 12/20 = 0.6 AB = 4/20 = 0.2 BB = 4/20 = 0.2Allele frequencies: in 20 people, there is a total of 40 alleles 12 AA individuals  24 A alleles 4 AB individuals  4 A alleles and 4 B alleles 4 BB individuals  8 B allelesFrequency of A alleles = (24 + 4)/40 = 0.7Frequency of B alleles = (8 + 4)/40 = 0.3Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*From genotype frequencies to allele frequenciesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.2The Hardy-Weinberg law correlates allele and genotype frequenciesDeveloped independently in 1908 by G.H. Hardy and W. WeinbergFive simplifying assumptions:The population has an infinite number of individualsIndividuals mate at randomNo new mutations appearNo migration into or out of the populationGenotypes have no effect on ability to survive and transmit alleles to the next generationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Predicting genotype frequencies in the next generationSexually reproducing, diploid organismsTwo steps needed to relate genotype frequencies in one generation to the next generationAllele frequencies should be the same in adults as in gametes Allele frequencies in gametes can be used to calculate expected genotype frequencies in zygotes of the next generationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*The Hardy-Weinberg law is a binomial equationIn a large population of randomly breeding individuals with no new mutations, no migration, and no differences in fitness based on genotype: p2 + 2pq + q2 = 1Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.3(Equation 19.1)Predicting the frequency of albinism: A case studyIn a population of 100,000 people:100 aa albinos, 1800 Aa carriers, 98,100 AA individualsTotal A alleles = (2 x 98,100) + 1800 = 198,000Total a alleles = (2 x 100) + 1800 = 2,000Frequency of A allele = p = 198,000/200,000 = 0.99Frequency of a allele = q = 2,000/200,000 = 0.01 p2 = (0.99)2 = 0.9801 2pq = 2(0.99)(0.01) = 0.0198 q2 = (0.01)2 = 0.0001Predicted genotypes in the next generation of 100,000 individuals:100,000 x 0.9801 = 98,010 AA individuals100,000 x 0.0198 = 1980 Aa individuals100,000 x 0.0001 = 10 aa individualsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*The population genetics of blue-eye colorBlue-eye color in humans is recessive to brown eyes and arose 6,000 – 10,000 years agoTrait is very common in Europe but rare outside of EuropeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.4aGeographic differences in proportions of European populations expressing the blue eyes phenotypeA SNP located in an enhancer of the OCA2 gene is associated with blue eye colorThe SNP rs12913832 is located in an intron of the HERC2 geneCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.4cFig 19.4bHaplotype structure of SNP alleles at the OCA2-HERC2 regionFrequencies of the A and G alleles of the SNP rs12913832 in different populationsp = rs12913832Aq = rs12913832G Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.4dUse of the Hardy-Weinberg equation with mixed populationsExample: Blue-eye phenotype in a population derived from 100 people from northern Finland and 100 people from Yakuts of eastern Siberiap = frequency of rs12913832A q = frequency of rs12913832GIn Finnish population of 100 people, q = 0.84 q2 = (0.84)2 = 0.71 2pq = 2 (0.16)(0.84) = 0.27 71 estimated to be GG (blue eyes) 27 estimated to be GA (brown-eyed carriers)In Yakut population of 100 people, q = 0.10 q2 = (0.1)2 = 0.01 2pq = 2 (0.9)(0.1) = 0.18 1 estimated to be GG (blue eyes) 18 estimated to be GA (brown-eyed carriers)Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Blue eyes vs. brown eyes in a mixed population (cont)Total population = 100 Finns + 100 Yakuts = 200 Total GG (blue eyes) = 71 Finns + 1 Yakut = 72 Total GA (carriers) = 27 Finns + 18 Yakuts = 45 Total number of G alleles = (2 x 72) + 45 = 189 Frequency of G alleles = q = 189/400 = 0.47Expected frequency of offspring with blue eyes (GG) from these 100 Finns and 100 Yakuts: q2 = (0.47)2 = 0.22 If 200 offspring, then 0.22 x 200 = 44 with blue eyes Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Properties of populations described by Hardy-Weinberg equilibriumConservation of allele proportionsEven though the genotype frequencies can change in the second generation, there will be no change in allele frequenciesA stratified population formed from two (or more) distinct populations will become balanced in a single generationAt Hardy-Weinberg equilibrium, genotype frequencies will be p2, 2pq, and q2Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Hardy-Weinberg provides a starting point for modeling population deviationsNatural populations rarely meet the simplified assumptions of Hardy-WeinbergNew mutations at each locus arise occasionallyNo population is infinitely largeMigrations of small groups of individuals does occurMating is not randomThere are genotype-specific differences in fitnessHardy-Weinberg equation is useful for estimating population changes through a few generationsNot as useful for predicting long-term changes, but does provide a foundation for modelingCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Using Monte Carlo simulations to model long-term changes in allele frequenciesMonte Carlo simulations use a computer program to model possible outcomes of randomly chosen matings over a designated number of generations Starting population has a defined number of individuals that are homozygous and heterozygousMating pairs are chosen through a random-number generating programGenotypes of offspring at each generation are based on probabilities Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Using Monte Carlo simulations to model long-term changes in allele frequencies (cont)At each generation in the simulation:Total offspring number and parental population size are equalParental generation is discarded and offspring serve as parents of next generationMultiple, independent simulations are performed Each simulation represents a possible pathway of genetic driftChange in allele frequencies as a consequence of random inheritance from one generation to the nextCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19* Modeling genetic drift in populations of different sizesSix Monte Carlo simulations run with two initial populations of heterozygous individualsIn these simulations, there was no selectionCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.5(a) Initial population has 10 individuals(b) Initial population has 500 individualsPopulation size and time to fixationFixation – when only one allele in a population has survived and all individuals are homozygous for that alleleNo further changes can occur (in the absence of migration or mutation)At each generation, changes in allele frequencies are relatively smallOver many generations, there can be large changes in allele frequencyIn populations with 2 alleles present at equal frequencies, median number of generations to fixation is roughly equal to the total number of gene copies in breeding individualse.g. Population of 10, median fixation time is 20 generationsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Founder effects and population bottlenecksFounder effects – occur when a few individuals separate from a larger populations and establish a new populationFounder allele frequencies can be different from original populationPopulation bottlenecks – large proportion of individuals die (e.g. from environmental disturbances)Survivors are equivalent to a founder populationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Natural selection acts on differences in fitness to alter allele frequenciesFitness – individual's relative ability to survive and transmit its genes to the next generation (a statistical measurement)Cannot be measured in individuals in a populationBut, can be measured in all individuals of the same genotype in a populationTwo basic components: viability and reproductive successNatural selection – the process that progressively eliminates individuals whose fitness is lower Individuals whose fitness is higher become the parents of the next generationOccurs in all natural populationsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Natural selection often acts through environmental conditionsNatural selection in giraffes on the savannahDuring long droughts, longer necks are needed to reach tree leavesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.6Giraffes with longer necks had higher fitness than giraffes with short necks Modifications to Hardy-WeinbergIn populations undergoing selection, each genotype has a relative fitnesse.g. Population with two allele (R and r)Relative fitness (ω) of each genotype (RR, Rr, and rr): ωRR ωRr ωrr Relative frequencies of each genotype at adulthood: p2ωRR 2pqωRr q2ωrrIndividual fitness for each genotype is arbitraryAverage fitness of the population: = p2ωRR + 2pqωRr + q2ωrr Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*ω(Equation 19.4a)Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.7Changes in allele frequencies caused by selectionCalculating the changes in allele frequencies due to selectionp' and q' represent allele frequencies after one generation of selectionCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*q' Δq = q' – q = s = selection coefficient Varies from 0 (no selection) to 1 (complete selection)If s = 0, Δq is always negativeRate of decrease depends on the allele frequenciesAs q approaches 0, rate of decrease gets slower (Fig 19.8)(Equation 19.5)(Equation 19.7)Predicted and observed decrease in the frequency of a lethal recessive allele over timeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.8An example of Monte Carlo modeling of natural selectionPopulation with 500 individuals (1 Rr, 499 rr) ωRR = 1.00 ωRr = 0.98 ωrr = 0.98 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.9Six simulations:In three simulations, R allele goes extinct in 450 species of mites and insects that had become resistantCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Changes in genotype frequencies in mosquitoes in response to DDTUse of DDT in Bangkok to control A. aegytpi mosquitoes - began in 1964 and discontinued in 1967 R is dominant, resistance allele; S is susceptibility alleleCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.14bRR genotype confers a fitness cost:In the absence of the insecticide, resistance is subject to negative selectionAnalyzing quantitative trait variationFactors causing continuous variation of quantitative traits Number of genes that determine the traitGenetic and environmental factors that affect penetrance and expressivity of the genesOne of the goals of quantitative analysis is to separate the genetics effects from the environmental effectsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Studies of dandelions can help sort out the effects of genes versus the environmentMost dandelion seeds arise from mitotic divisions – all seeds from a single plant are genetically identicalGoal is to compare influence of genes and environment on the length of the stem at floweringCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.15aFinding the mean and variance of stem length in dandelionsGenetically identical plants grown on hillside: Variation in stem length should be a consequence of environmental interactions (VE)Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.15bGenetically identical dandelions grown in two environmentsVE for growth in greenhouse < VE for growth on hillsideThis difference in VE is a measure of the impact of the more diverse environmental conditions on the hillside Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.15cGrowth of genetically identical and genetically diverse dandelions in a greenhouseDifference in variance between genetically diverse and identical plants is VG, the genetic varianceCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.15dCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.15eGrowth of genetically identical and genetically diverse dandelions on a hillsideTotal phenotype variance (VP) = VE + VGHeritability is the proportion of phenotypic variance due to genetic varianceCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*(Equation 19.11)Heritability of a trait is always defined for a specific population in a specific set of environmental conditionsAmounts of genetic, environmental, and phenotypic variation may differ among traitsHeritability is measured in studies of groups with defined genetic differencesMeasuring the heritability of bill depth in populations of Darwin’s finchesGeospiza fortis on Daphne Major in the Galápagos IslandsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Correlation between beak size of offspring and the average of the parents' beak sizes (slope of line is 0.82)Fig 19.16a, bResults if finch populations had no environmental or no genetic effectsApproximately 82% of variation in bill depth in Darwin's finches is due to genetic variation among individuals (Fig 19.16b, slope of line is 0.82)If the environment had no effect, then heritability would be 1.0If there was not genetic contribution, then heritability would be 0 Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.16c, dHeritability of polygenic traits in humans can be studied using twinsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.17aConcordance of a trait in two children raised in the same familyIf the heritability is 0.0, no differences would be observed between monozygotic (MZ), dizygotic (DZ), or unrelated by adoption (UR)Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.17bConcordance of a trait in two children raised in the same family (cont)If the heritability is 1.0, differences would be observed in comparing monozygotic (MZ), dizygotic (DZ), or unrelated by adoption (UR)The extent of difference varies with the trait frequencyCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.17bA trait's heritability determines its potential for evolutionHeritability quantifies the potential for selectionA trait with high heritability has a large potential for evolutionSelection differential = SDifference between value for this trait in the parents and value for this trait in the entire population (breeding and non-breeding) Response to selection = RThe amount of change in the mean value of a trait that results from selectionR = h2SCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*(Equation 19.12)Bristle number in parents and offspring in a lab population of D. melanogasterCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.18This trait has a high heritability: Parents with high bristle numbers have offspring with high bristle numbersParents with low bristle numbers have offspring with low bristle numbersEvolution of abdominal bristle number in response to artificial selection in DrosophilaArtificial selection can be imposed on this trait – Flies with high bristle number bred togetherFlies with low bristle number bred togetherCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th edition, Chapter 19*Fig 19.19