9781405132770

Table of Contents


	Preface and Acknowledgments	xi
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	6
	Interact Box 1.1 The Textbook Website	7
	Chapter 1 Review	8
	Further Reading	8
2	Genotype Frequencies	9
2.1	Mendel�s Model of Particulate Genetics	9
2.2	Hardy�Weinberg Expected Genotype Frequencies	13
	Interact Box 2.1 Genotype Frequencies	14
2.3	Why does Hardy�Weinberg Work?	17
2.4	Applications of Hardy�Weinberg	19
	Forensic DNA Profiling	19
	Problem Box 2.1 The Expected Genotype Frequency for a DNA Profile	22
	Testing for Hardy�Weinberg	22
	Box 2.1 DNA Profiling	22
	Interact Box 2.2 χ² Test	26
	Assuming Hardy�Weinberg to Test Alternative Models of Inheritance	26
	Problem Box 2.2 Proving Allele Frequencies are Obtained from Expected Genotype Frequencies	27
	Problem Box 2.3 Inheritance for Corn Kernel Phenotypes	28
2.5	The Fixation Index and Heterozygosity	28
	Interact Box 2.3 Assortative Mating and Genotype Frequencies	29
	Box 2.2 Protein Locus or Allozyme Genotyping	32
2.6	Mating Among Relatives	33
	Impacts of Inbreeding on Genotype and Allele Frequencies	33
	Inbreeding Coefficient and Autozygosity in a Pedigree	34
	Phenotypic Consequences of Inbreeding	37
	The Many Meanings of Inbreeding	40
2.7	Gametic Disequilibrium	41
	Interact Box 2.4 Decay of Gametic Disequilibrium and a χ² Test	44
	Physical Linkage	45
	Natural Selection	46
	Interact Box 2.5 Gametic Disequilibrium Under Both Recombination and Natural Selection	46
	Mutation	47
	Mixing of Diverged Populations	47
	Mating System	48
	Chance	48
	Interact Box 2.6 Estimating Genotypic Disequilibrium	49
	Chapter 2 Review	50
	Further Reading	50
	Problem Box Answers	51
3	Genetic Drift and Effective Population Size	53
3.1	The Effects of Sampling Lead to Genetic Drift	53
	Interact Box 3.1 Genetic Drift	58
3.2	Models of Genetic Drift	58
	The Binomial Probability Distribution	58
	Problem Box 3.1 Applying the Binomial Formula	60
	Math Box 3.1 Variance of a Binomial Variable	62
	Markov Chains	62
	Interact Box 3.2 Genetic Drift Simulated with a Markov Chain Model	65
	Problem Box 3.2 Constructing a Transition Probability Matrix	66
	The Diffusion Approximation of Genetic Drift	67
3.3	Effective Population Size	73
	Problem Box 3.3 Estimating N_e from Information About N	77
3.4	Parallelism Between Drift and Inbreeding	78
3.5	Estimating Effective Population Size	80
	Interact Box 3.3 Heterozygosity, and Inbreeding Over Time in Finite Populations	81
	Different Types of Effective Population Size	82
	Problem Box 3.4 Estimating N_e from Observed Heterozygosity Over Time	85
	Breeding Effective Population Size	85
	Effective Population Sizes of Different Genomes	87
3.6	Gene Genealogies and the Coalescent Model	87
	Math Box 3.2 Approximating the Probability of a Coalescent Event with the Exponential Distribution	93
	Interact Box 3.4 Build Your Own Coalescent Genealogies	94
3.7	Effective Population Size in the Coalescent Model	96
	Interact Box 3.5 Simulating Gene Genealogies in Populations with Different Effective Sizes	97
	Coalescent Genealogies and Population Bottlenecks	98
	Coalescent Genealogies in Growing and Shrinking Populations	99
	Interact Box 3.6 Coalescent Genealogies in Populations with Changing Size	101
	Chapter 3 Review	101
	Further Reading	102
	Problem Box Answers	103
4	Population Structure and Gene Flow	105
4.1	Genetic Populations	105
	Method Box 4.1 Are Allele Frequencies Random or Clumped in Two Dimensions?	110
4.2	Direct Measures of Gene Flow	111
	Problem Box 4.1 Calculate the Probability of a Random Haplotype Match and the Exclusion Probability	117
	Interact Box 4.1 Average Exclusion Probability for a Locus	117
4.3	Fixation Indices to Measure the Pattern of Population Subdivision	118
	Problem Box 4.2 Compute F_IS, F_ST, and F_IT	122
	Method Box 4.2 Estimating Fixation Indices	124
4.4	Population Subdivision and the Wahlund Effect	124
	Interact Box 4.2 Simulating the Wahlund Effect	127
	Problem Box 4.3 Account for Population Structure in a DNA-Profile Match Probability	130
4.5	Models of Population Structure	131
	Continent-Island Model	131
	Interact Box 4.3 Continent-Island Model of Gene Flow	134
	Two-Island Model	134
	Infinite Island Model	135
	Interact Box 4.4 Two-Island Model of Gene Flow	136
	Math Box 4.1 The Expected Value of F_ST in the Infinite Island Model	138
	Problem Box 4.4 Expected Levels of F_ST for Y-Chromosome and Organelle Loci	139
	Interact Box 4.5 Fin Ite Island Model of Gene Flow	139
	Stepping-Stone and Metapopulation Models	141
4.6	The Impact of Population Structure on Genealogical Branching	142
	Combining Coalescent and Migration Events	143
	The Average Length of a Genealogy with Migration	144
	Interact Box 4.6 Coalescent Events in Two Demes	145
	Math Box 4.2 Solving Two Equations with Two Unknowns for Average Coalescence Times	148
	Chapter 4 Review	149
	Further Reading	150
	Problem Box Answers	151
5	Mutation	154
5.1	The Source of All Genetic Variation	154
5.2	The Fate of a New Mutation	160
	Chance a Mutation is Lost Due to Mendelian Segregation	160
	Fatcofa New Mutation in a Finite Population	162
	Interact Box 5.1 Frequency of Neutral Mutations in a Finite Population	163
	Geometric Model of Mutations Fixed by Natural Selection	164
	Muller�s Ratchet and the Fixation of Deleterious Mutations	166
	Interact Box 5.2 Muller�s Ratchet	168
5.3	Mutation Models	168
	Mutation Models for Discrete Alleles	169
	Interact Box 5.3 R_ST and F_ST as Examples of the Consequences of Different Mutation Models	172
	Mutation Models for DNA Sequences	172
5.4	The Influence of Mutation on Allele Frequency and Autozygosity	173
	Math Box 5.1 Equilibrium Allele Frequency with Two-Way Mutation	176
	Interact Box 5.4 Simulating Irreversible and Bi-Directional Mutation	177
5.5	The Coalescent Model with Mutation	178
	Interact Box 5.5 Build Your Own Coalescent Genealogies with Mutation	181
	Chapter 5 Review	183
	Further Reading	183
6	Fundamentals of Natural Selection	185
6.1	Natural Selection	185
	Natural Selection with Clonal Reproduction	185
	Problem Box 6.1 Relative Fitness of HIV Genotypes	189
	Natural Selection with Sexual Reproduction	189
6.2	General Results for Natural Selection on a Diallelic Locus	193
	Math Box 6.1 The Change in Allele Frequency Each Generation Under Natural Selection	194
	Selection Against a Recessive Phenotype	195
	Selection Against a Dominant Phenotype	196
	General Dominance	197
	Heterozygote Disadvantage	198
	Heterozygote Advantage	198
	The Strength of Natural Selection	199
	Math Box 6.2 Equilibrium Allele Frequency with Overdominance	200
6.3	How Natural Selection Works to Increase Average Fitness	200
	Average Fitness and Rate of Change in Allele Frequency	201
	Problem Box 6.2 Mean Fitness and Change in Allele Frequency	203
	The Fundamental Theorem of Natural Selection	203
	Interact Box 6.1 Natural Selection on One Locus with Two Alleles	203
	Chapter 6 Review	206
	Further Reading	206
	Problem Box Answers	206
7	Further Models of Natural Selection	208
7.1	Viability Selection with Three Alleles or Two Loci	208
	Natural Selection on One Locus with Three Alleles	209
	Problem Box 7.1 Marginal Fitness and Δp for the Hb C Allele	211
	Interact Box 7.1 Natural Selection on One Locus with Three or More Alleles	211
	Natural Selection on Two Diallelic Loci	212
7.2	Alternative Models of Natural Selection	216
	Natural Selection via Different Levels of Fecundity	216
	Natural Selection with Frequency-Dependent Fitness	218
	Natural Selection with Density-Dependent Fitness	219
	Math Box 7.1 The Change in Allele Frequency with Frequency-Dependent Selection	219
	Interact Box 7.2 Frequency-Dependent Natural Selection	220
	Interact Box 7.3 Density-Dependent Natural Selection	222
7.3	Combining Natural Selection with Other Processes	222
	Natural Selection and Genetic Drift Acting Simultaneously	222
	Interact Box 7.4 The Balance of Natural Selection and Genetic Drift at a Diallelic Locus	224
	The Balance Between Natural Selection and Mutation	225
	Interact Box 7.5 Natural Selection and Mutation	226
7.4	Natural Selection in Genealogical Branching Models	226
	Directional Selection and the Ancestral Selection Graph	227
	Problem Box 7.2 Resolving Possible Selection Events on an Ancestral Selection Graph	230
	Genealogies and Balancing Selection	230
	Interact Box 7.6 Coalescent Genealogies with Directional Selection	231
	Chapter 7 Review	232
	Further Reading	233
	Problem Box Answers	234
8	Molecular Evolution	235
8.1	The Neutral Theory	235
	Polymorphism	236
	Divergence	237
	Nearly Neutral Theory	240
	Interact Box 8.1 The Relative Strengths of Genetic Drift and Natural Selection	241
8.2	Measures of Divergence and Polymorphism	241
	Box 8.1 DNA Sequencing	242
	DNA Divergence Between Species	242
	DNA Sequence Divergence and Saturation	243
	DNA Polymorphism	248
8.3	DNA Sequence Divergence and the Molecular Clock	250
	Interact Box 8.2 Estimating N and S from DNA Sequence Data	251
	Dating Events with the Molecular Clock	252
	Problem Box 8.1 Estimating Divergence Times with the Molecular Clock	254
8.4	Testing the Molecular Clock Hypothesis and Explanations for Rate Variation in Molecular Evolution	255
	The Molecular Clock and Rate Variation	255
	Ancestral Polymorphism and Poisson Process Molecular Clock	257
	Math Box 8.1 The Dispersion Index with Ancestral Polymorphism and Divergence	259
	Relative Rate Tests of the Molecular Clock	260
	Patterns and Causes of Rate Heterogeneity	261
8.5	Testing the Neutral Theory Null Model of DNA Sequence Evolution	265
	HKA Test of Neutral Theory Expectations for DNA Sequence Evolution	265
	MK Test	267
	Tajima�s D	269
	Problem Box 8.2 Computing Tajima�s D from DNA Sequencedata	271
	Mismatch Distributions	272
	Interact Box 8.3 Mismatch Distributions for Neutral Genealogies in Stable, Growing, or Shrinking Populations	274
8.6	Molecular Evolution of Loci that are Not Independent	274
	Genetic Hitch-Hiking Due to Background or Balancing Selection	278
	Gametic Disequilibrium and Rates of Divergence	278
	Chapter 8 Review	279
	Further Reading	280
	Problem Box Answers	281
9	Quantitative Trait Variation and Evolution	283
9.1	Quantitative Traits	283
	Problem Box 9.1 Phenotypic Distribution Produced by Mendelian Inheritance of Three Diallelic Loci	285
	Components of Phenotypic Variation	286
	Components of Genotypic Variation (V_G)	288
	Inheritance of Additive (V_A), Dominance (V_D), Andepistasis (V_I) Genotypic Variation	291
	Genotype-by-Environment Interaction (V_G�E)	292
	Additional Sources of Phenotypic Variance	295
	Math Box 9.1 Summing Two Variances	296
9.2	Evolutionary Change in Quantitative Traits	297
	Heritability	297
	Changes in Quantitative Trait Mean and Variance Due to Natural Selection	299
	Estimating Heritability by Parent�Offspring Regression	302
	Interact Box 9.1 Estimating Heritability with Parent�Offspring Regression	303
	Response to Selection on Correlated Traits	304
	Interact Box 9.2 Response to Natural Selection on Two Correlated Traits	306
	Long-Term Response to Selection	307
	Interact Box 9.3 Response to Selection and the Number of Loci that Cause Quantitative Trait Variation	309
	Neutral Evolution of Quantitative Traits	313
	Interact Box 9.4 Effective Population Size and Genotypic Variation in a Neutral Quantitative Trait	314
9.3	Quantitative Trait Loci (QTL)	315
	QTL Mapping with Single Marker Loci	316
	Problem Box 9.2 Compute the Effect and Dominance Coefficient of a QTL	321
	QTL Mapping with Multiple Marker Loci	322
	Problem Box 9.3 Derive the Expected Marker-Class Means for a Backcross Mating Design	324
	Limitations of QTL Mapping Studies	325
	Biological Significance of QTL Mapping	326
	Interact Box 9.5 Effect Sizes and Response to Selection at QTLs	328
	Chapter 9 Review	330
	Further Reading	330
	Problem Box Answers	331
10	The Mendelian Basis of Quantitative Trait Variation	334
10.1	The Connection Between Particulate Inheritance and Quantitative Trait Variation	334
	Scale of Genotypic Values	334
	Problem Box 10.1 Compute Values on the Genotypic Scale of Measurement for IGF1 in Dogs	335
10.2	Mean Genotypic Value in a Population	336
10.3	Average Effect of an Allele	337
	Math Box 10.1 The Average Effect of the A₁ Allele	339
	Problem Box 10.2 Compute the Allele Average Effect of the IGF1 A₂ Allele in Dogs	341
10.4	Breeding Value and Dominance Deviation	341
	Interact Box 10.1 Average Effects, Breeding Values, and Dominance Deviations	345
	Dominance Deviation	345
10.5	Components of Total Genotypic Variance	348
	Interact Box 10.2 Components of Total Genotypic Variance, V_G	350
	Math Box 10.2 Deriving the Total Genotypic Variance, V_G	350
10.6	Genotypic Resemblance Between Relatives	351
	Chapter 10 Review	354
	Further Reading	354
	Problem Box Answers	355
11	Historical and Synthetic Topics	356
11.1	Historical Controversies in Population Genetics	356
	The Classical and Balance Hypotheses	356
	How to Explain Levels of Allozyme Polymorphism	358
	Genetic Load	359
	Math Box 11.1 Mean Fitness in a Population at Equilibrium for Balancing Selection	362
	The Selectionist/Neutralist Debates	363
11.2	Shifting Balance Theory	366
	Allele Combinations and the Fitness Surface	366
	Wright�s View of Allele-Frequency Distributions	368
	Evolutionary Scenarios Imagined by Wright	369
	Critique and Controversy Over Shifting Balance	372
	Chapter 11 Review	374
	Further Reading	374
	Appendix	376
	Statistical Uncertainty	376
	Problem Box A.1 Estimating the Variance	378
	Interact Box A.1 The Central Limit Theorem	379
	Covariance and Correlation	380
	Further Reading	382
	Problem Box Answers	382
	References	383
	Index	396