MATTHEW B. HAMILTON, PHD, is Associate Professor of Biology at Georgetown University, where he teaches Population Genetics, Molecular Evolution, Evolutionary Processes, and similar undergraduate and graduate level courses. He is founding Director of Georgetown's Environmental Biology undergraduate major, past Director of the Georgetown Environment Initiative, and currently conducts research on the processes that influence the distribution of genetic variation within species.

Preface and acknowledgements xiv

About the companion websites xvi

1 Thinking like a population geneticist 1

1.1 Expectations 1

Parameters and parameter estimates 2

Inductive and deductive reasoning 3

1.2 Theory and assumptions 4

1.3 Simulation 5

Interact box 1.1 The textbook website 6

Chapter 1 review 7

Further reading 7

2 Genotype frequencies 8

2.1 Mendel's model of particulate genetics 8

2.2 Hardy-Weinberg expected genotype frequencies 12

Interact box 2.1 Genotype frequencies for one locus with two alleles 14

2.3 Why does Hardy-Weinberg work? 15

2.4 Applications of Hardy-Weinberg 18

Forensic DNA profiling 18

Problem box 2.1 The expected genotype frequency for a DNA profile 20

Testing Hardy-Weinberg expected genotype frequencies 20

Box 2.1 DNA profiling 21

Assuming Hardy-Weinberg to test alternative models of inheritance 24

Problem box 2.2 Proving allele frequencies are obtained from expected genotype frequencies 25

Problem box 2.3 Inheritance for corn kernel phenotypes 26

2.5 The fixation index and heterozygosity 26

Interact box 2.2 Assortative mating and genotype frequencies 27

Box 2.2 Protein locus or allozyme genotyping 30

2.6 Mating among relatives 31

Impacts of non-random mating on genotype and allele frequencies 31

Coancestry coefficient and autozygosit, 33

Box 2.3 Locating relatives using genetic genealogy methods 37

Phenotypic consequences of mating among relatives 38

The many meanings of inbreeding 41

2.7 Hardy-Weinberg for two loci 42

Gametic disequilibrium 42

Physical linkage 47

Natural selection 47

Interact box 2.3 Gametic disequilibrium under both recombination and natural selection 48

Mutation 48

Mixing of diverged populations 49

Mating system 49

Population size 50

Interact box 2.4 Estimating genotypic disequilibrium 51

Chapter 2 review 52

Further reading 52

End-of-chapter exercises 53

Problem box answers 54

3 Genetic drift and effective population size 57

3.1 The effects of sampling lead to genetic drift 57

Interact box 3.1 Genetic drift 62

3.2 Models of genetic drift 62

The binomial probability distribution 62

Problem box 3.1 Applying the binomial formula 64

Math box 3.1 Variance of a binomial variable 66

Markov chains 66

Interact box 3.2 Genetic drift simulated with a markov chain model 69

Problem box 3.2 Constructing a transition probability matrix 69

The diffusion approximation of genetic drift 70

3.3 Effective population size 76

Problem box 3.3 Estimating N e from information about N 81

3.4 Parallelism between Drift and mating among relatives 81

Interact box 3.3 Heterozygosity over time in a finite population 84

3.5 Estimating effective population size 85

Different types of effective population size 85

Interact box 3.4 Estimating N e from allele frequencies and heterozygosity over time 89

Breeding effective population size 90

Effective population sizes of different genomes 92

3.6 Gene genealogies and the coalescent model 92

Interact box 3.5 Sampling lineages in a Wright-Fisher population 94

Math box 3.2 Approximating the probability of a coalescent event with the exponential distribution 99

Interact box 3.6 Build your own coalescent genealogies 100

3.7 Effective population size in the coalescent model 103

Interact box 3.7 Simulating gene genealogies in populations with different effective sizes 103

Coalescent genealogies and population bottlenecks 105

Coalescent genealogies in growing and shrinking populations 106

Interact box 3.8 Coalescent genealogies in populations with changing size 107

3.8 Genetic drift and the coalescent with other models of life history 108

Chapter 3 review 110

Further reading 111

End of chapter exercises 111

Problem box answers 113

4 Population structure and gene flow 115

4.1 Genetic populations 115

Box 4.1 Are allele frequencies random or clumped in two dimensions? 121

4.2 Gene flow and its impact on allele frequencies in multiple subpopulations 122

Continent-island model 123

Two-island model 125

Interact box 4.1 Continent-island model of gene flow 125

Interact box 4.2 Two-island model of gene flow 126

4.3 Direct measures of gene flow 127

Problem box 4.1 Calculate the probability of a random haplotype match and the exclusion probability 133

Interact box 4.3 Average exclusion probability for a locus 134

4.4 Fixation indices to summarize the pattern of population subdivision 135

Problem box 4.2 Compute FIS, FST, and FIT 138

Estimating fixation indices 140

4.5 Population subdivision and the Wahlund effect 142

Interact box 4.4 Simulating the Wahlund effect 144

Problem box 4.3 Impact of population structure on a DNA-profile match probability 147

4.6 Evolutionary models that predict patterns of population structure 148

Infinite island model 148

Math box 4.1 The expected value of F ST in the infinite island model 150

Problem box 4.4 Expected levels of F ST for Y-chromosome and organelle loci 153

Interact box 4.5 Simulate FIS, FST, and FIT in the finite island model 154

Stepping-stone and metapopulation models 155

Isolation by distance and by landscape connectivity 156

Math box 4.2 Analysis of a circuit to predict gene flow across a landscape 159

4.7 Population assignment and clustering 160

Maximum likelihood assignment 161

Bayesian assignment 161

Interact box 4.6 Genotype assignment and clustering 162

Math box 4.3 Bayes Theorem 166

Empirical assignment methods 167

Interact box 4.7 Visualizing principle components analysis 167

4.8 The impact of population structure on genealogical branching 169

Combining coalescent and migration events 169

Interact box 4.8 Gene genealogies with migration between two demes 171

The average length of a genealogy with migration 172

Math box 4.4 Solving two equations with two unknowns for average coalescence times 175

Chapter 4 review 176

Further reading 177

End of chapter exercises 178

Problem box answers 180

5 Mutation 183

5.1 The source of all genetic variation 183

Estimating mutation rates 187

Evolution of mutation rates 189

5.2 The fate of a new mutation 191

Chance a mutation is lost due to mendelian segregation 191

Fate of a new mutation in a finite population 193

Interact box 5.1 Frequency of neutral mutations in a finite population 194

Mutations in expanding populations 195

Geometric model of mutations fixed by natural selection 196

Muller's ratchet and the fixation of deleterious mutations 199

Interact box 5.2 Muller's Ratchet 201

5.3 Mutation models 201

Mutation models for discrete alleles 201

Interact box 5.3 Rst and Fst as examples of the consequences of different mutation models 204

Mutation models for DNA sequences 205

Box 5.1 Single nucleotide polymorphisms 206

5.4 The influence of mutation on allele frequency and autozygosity 207

Math box 5.1 Equilibrium allele frequency with two-way mutation 209

Interact box 5.4 Simulating irreversible and two-way mutation 211

Interact box 5.5 Heterozygosity and homozygosity with two-way mutation 212

5.5 The coalescent model with mutation 213

Interact box 5.6 Build your own coalescent genealogies with mutation 215

Chapter 5 review 217

Further reading 218

End-of-chapter exercises 219

6 Fundamentals of natural selection 220

6.1 Natural selection 220

Natural selection with clonal reproduction 220

Problem box 6.1 Relative fitness of HIV genotypes 224

Natural selection with sexual reproduction 225

Math box 6.1 The change in allele frequency each generation under natural selection 229

6.2 General results for natural selection on a diallelic locus 230

Selection against a recessive phenotype 231

Selection against a dominant phenotype 232

General dominance 233

Heterozygote disadvantage 234

Heterozygote advantage 235

Math box 6.2 Equilibrium allele frequency with overdominance 236

The strength of natural selection 237

6.3 How natural selection works to increase average fitness 238

Average fitness and rate of change in allele frequency 238

Problem box 6.2 Mean fitness and change in allele frequency 240

Interact box 6.1 Natural selection on one locus with two alleles 240

The fundamental theorem of natural selection 241

6.4 Ramifications of the one locus, two allele model of natural selection 243

The Classical and Balance Hypotheses 243

How to explain levels of allozyme polymorphism, 245

Chapter 6 review 246

Further reading 247

End-of-chapter exercises 247

Problem box answers 248

7 Further models of natural selection 250

7.1 Viability selection with three alleles or two loci 250

Natural selection on one locus with three alleles 250

Problem box 7.1 Marginal fitness and ¿p for the Hb C allele 253

Interact box 7.1 Natural selection on one locus with three or more alleles 254

Natural selection on two diallelic loci 254

7.2 Alternative models of natural selection 259

Natural selection via different levels of...