Table of Contents<br> <br>PREFACE XI<br>m GENETIC AND STATISTICAL<br>111 BACKGROUND 1<br>Gene Expression and Gene Interaction 2<br>Gene Expression 3<br>The Genetic Code 6<br>Alkies 8<br>Genotype and Phenotype 8<br>Dominance and Gene Interaction 11<br>Segregation and Recombination 12 Probability in Population Genetics 15<br>The Addition Rule 16<br>The Multiplication Rule 16<br>Repeated Trials 17 Phenotypic Diversity and Genetic Variation 20<br>Allele Frequencies in Populations 20<br>Parameters and Estimates 22<br>The Standard Error of an Estimate 22 Models in Population Genetics 26<br>Exponential Population Growth 27<br>Logistic Population Growth 31 Summary 33 Problems 34<br>B<br> GENETIC AND PHENOTYPIC VARIATION 37<br>Phenotypic Variation in Natural Populations 37<br>Continuous Variation: The Normal Distribution 38 Mean and Variance 39<br> <br>Central Limit Theorem 41 Discrete Mendelian Variation 43 Experimental Methods for Detecting Genetic Variation 44<br>Protein Electrophoresis 45 The Southern Blot Procedure 48 The Polymerase Chain Reaction 51<br>Polymorphism and Heterozygosity 53 Allozyme Polymorphisms 54 How Representative Are Allozymes ? 56 Polymorphisms in DNA Sequences 57 Nucleotide Polymorphism and Nucleotide<br>Diversity 57 Uses of Genetic Polymorphisms 62<br>Multiple-Factor Inheritance 64<br>Summary 66<br>Problems 68<br>B<br> ORGANIZATION OF GENETIC VARIATION 74<br>Random Mating 72<br>Nonoverlapping Generations 73 The Hardy-Weinberg Principle 74 Random Mating of Genotypes versus<br>Random Union of Gametes 76 Implications of the Hardy-Weinberg<br>Principle 79 The Hardy-Weinberg Principle in<br>Operation 80<br>Complications of Dominance 84 Frequency of Heterozygotes 87 Special Cases of Random Mating 88 Three or More Alleles 88 X-Linked Genes 92<br> <br>Linkage and Linkage Disequilibrium<br>95<br>Summary 106 Problems 107<br>fj POPULATION SUBSTRUCTURE<br>Hierarchical Population Structure 111<br>Reduction in Heterozygosity 112 Average Heterozygosity 114 Wright’s F Statistics 117 Genetic Divergence among Subpopulations 120<br>Isolate Breaking: The Wahlund Principle 122<br>Wahlund’s Principle and the Fixation Index 125<br>Genotype Frequencies in Subdivided Populations 127<br>Population Genetics in DNA Typing 128<br>Polymorphisms Based on a Variable Number of Tandem Repeats (VNTR) 129<br>Match Probabilities with Hardy-Weinberg Equilibrium and Linkage Equilibrium 132<br>Effects of Population Substructure 132 Inbreeding 135<br>Genotype Frequencies with Inbreeding 135<br>Relation between the Inbreeding Coefficient and the F Statistics 139<br>The Inbreeding Coefficient as a Probability 141<br>Genetic Effects of Inbreeding 145<br>Calculation of the Inbreeding Coefficient from Pedigrees 149<br>Regular Systems of Mating 153 Assortative Mating 155 Summary 158 Problems 159<br> <br>U SOURCES OF VARIATION 163<br>Mutation 163<br>Irreversible Mutation 164<br>Reversible Mutation 168<br>Probability of Fixation of a New Neutral Mutation 170<br>The Infinite-Alleles Model 174<br>Neutral Mutations 177 Linkage and Recombination 180<br>Presumed Evolutionary Benefit of Recombination 181<br>Recombination and Polymorphism 181<br>Piecewise Recombination in Bacteria 186<br>Absence of Recombination in Animal Mitochondrial DNA 187<br>Migration 189<br>One-Way Migration 189<br>The Island Model of Migration 192<br>How Migration Limits Genetic Divergence<br>194<br>Estimates of Migration Rates 196 Patterns of Migration 196 Transposable Elements 198<br>Factors Controlling the Population Dynamics of Transposable Elements 200 Insertion Sequences and Composite Trans-<br>posons in Bacteria 200 Transposable Elements in Eukaryotes 204 Horizontal Transmission of Transposable Elements 204<br>Summary 206 Problems 208<br>Qj DARWINIAN SELECTION 211<br>Selection in Haploid Organisms 212<br>Discrete Generations 212 Continuous Time 216 Change in Allele Frequency in Haploids 217<br> <br>Q<br>Darwinian Fitness and Malthusian Fitness<br>218<br>Selection in Diploid Organisms 218<br>Change in Allele Frequency in Diploids<br>219 Time Required for a Given Change in Allele<br>Frequency 222 Application to the Evolution of Insecticide<br>Resistance 226<br>Equilibria with Selection 227<br>Overdominance 228 Local Stability 232 Heterozygote Inferiority 234 The Adaptive Topography and the Role of Random Genetic Drift 236<br>Mutation-Selection Balance 236<br>Equilibrium Allele Frequencies 237 The Haldane-Muller Principle 239<br>More Complex Types of Selection 240 Frequency-Dependent Selection 240 Density-Dependent Selection 241 Fecundity Selection 241 Age-Structured Populations 242 Heterogeneous Environments and dines<br>242<br>Diversifying Selection 244 Differential Selection in the Sexes 246 X-linked Genes 246 Gametic Selection 246 Meiotic Drive 247 Multiple Alleles 250 Multiple Loci and Gene Interaction:<br>Epistasis 252 Sexual Selection 255<br>Kin Selection 256<br>Interdeme Selection and the Shifting Balance Theory 259<br>Summary 262<br>Problems 264<br> <br>RANDOM GENETIC DRIFT 267<br>Random Genetic Drift and Binomial<br>Sampling 267 The Wright-Fisher Model of Random<br>Genetic Drift 274 The Diffusion Approximation 277<br>Absorption Time and Time to Fixation 282 Parallelism between Random Drift and<br>Inbreeding 283 Effective Population Size 289 Fluctuation in Population Size 290 Unequal Sex Ratio, Sex Chromosomes, Organelle Genes 292<br>Balance between Mutation and Drift<br>294 Infinite Alleles Model 294<br>The Ewens Sampling Formula 296 The Ewens-Watterson Test 298<br>Infinite-Sites Model 300<br>Gene Trees and the Coalescent 304 Coalescent Models with Mutation 308<br>Summary 310<br>Problems 312<br>Q<br> MOLECULAR POPULATION GENETICS 315<br>The Neutral Theory and Molecular Evolution 315<br>Theoretical Principles of the Neutral Theory 316<br>Estimating Rates of Molecular Sequence Divergence 320<br>Rates ofAmino Acid Replacement 320 Rates ofNucleotide Substitution 324 Other Measures of Molecular Divergence 327<br>The Molecular Clock 328<br>Variation across Genes in the Rate of the Molecular Clock 331<br> <br>Variation across Lineages in Clock Rate<br>333<br>The Generation-Time Effect 336 Does the Constancy of Substitution Rates<br>Prove the Neutral Theory? 337<br>Patterns of Nucleotide and Amino Acid Substitution 338<br>Calculating Synonymous and Nonsynony-<br>mous Substitution Rates 338 Within-Species Polymorphism 345 Implications ofCodon Bias 348 Polymorphism and Divergence in<br>Nucleotide Sequence Data 349 Impact of Local Recombination Rates 353 Gene Genealogies 354<br>Hypothesis Testing Using Trees 356 Inferences about Migration Based on Gene Trees 360<br>Mitochondrial and Chloroplast DNA Evolution 361<br>Chloroplast DNA and Organelle<br>Transmission in Plants 365 Maintenance of Variation in Organelle<br>Genomes 366<br>Evidence for Selection in mtDNA 367 Molecular Phylogenetics 368 Algorithms for Phylogenetic Tree<br>Reconstruction 368<br>Distance Methods versus Parsimony 372 Bootstrapping and Statistical Confidence<br>in a Tree 372 Shared Polymorphism 373 Interspecific Genetics 374 Multigene Families 374<br>Causes of Concerted Evolution 375 Multigene Family Evolution through a<br>Birth and Death Process 378 Structural RNA Genes and Compensatory<br>Substitutions 382 Multigene Superfamilies 383<br> <br>Dispersed Highly Repetitive DNA Sequences 385<br>Summary 390 Problems 392<br>Q QUANTITATIVE GENETICS 397<br>Types of Quantitative Traits 398 Resemblance between Relatives and<br>the Concept of Heritability 400 Artificial Selection and

Realized<br>Heritability 406 Prediction Equation for Individual<br>Selection 407 Selection Limits 411 Genetic Models for Quantitative Traits<br>414<br>Change in Gene Frequency 421 Genetic Model for the Change in Mean Phenotype 423<br>Components of Phenotypic Variance 424<br>Genetic and Environmental Sources of<br>Variation 425<br>Components ofGenotypic Variation 430 Covariance between Relatives 434 Twin Studies and Inferences of Heritability in Humans 440<br>Experimental Assessment of Genetic Variance Components 442<br>Indirect Estimation of the Number of Genes Affecting a Quantitative Character 445<br>Norm of Reaction and Phenotypic<br>Plasticity 448 Threshold Traits and the Genetics of<br>Liability 452 Correlated Response and Genetic<br>Correlation 454 Inference of Selection from Phenotypic<br>Data 458<br>Evolution of Quantitative Traits 460<br> <br>Random Genetic Drift and Phenotypic SUGGESTIONS FOR FURTHER<br>Evolution 461 READING 483<br>Mutation-Selection Balance 465<br>Quantitative Trait Loci 467 ANSWERS TO CHAPTER-END<br>Quantitative Trait Loci 467 PROBLEMS 487<br>Mapping Genes that Influence<br>Quantitative Characters 467 BIBLIOCRAPHY 50S<br>Significance Testing ofQTLs 470<br>Composite Interval Mapping and AUTHOR INDFX S91<br>Other Refinements 471 AUIHUKINUtA bZl<br>What Have We Learned from Mapping<br>QTLs? 473 SUBJECT INDEX 525<br>Summary 476 Problems 479<br>