Principles of Population Genetics

Citation

Hartl, D. L., & Clark, A. G. (2007). Principles of Population Genetics (4th ed.). Sinauer Associates.

Chapter Summary

The book has ten chapters, about 565 pages of main text by the publisher's count, followed by a section of answers to chapter-end problems (about thirty pages), a bibliography and author and subject indexes. The publisher describes the aim as a balanced presentation of theory and observation for undergraduate and graduate students and for newcomers from fields such as human genetics. Each chapter ends with a summary and problems. Chapter titles below follow the publisher's table of contents, and the descriptions draw on its section headings and its chapter-by-chapter overview.

Chapter 1: Genetic and Phenotypic Variation

The opening chapter introduces the observations and the means of quantifying the amount and structure of genetic variation in natural populations. Its sections cover phenotypic variation (the normal distribution, mean and variance, the central limit theorem, Mendelian variation), multiple-factor inheritance, the maintenance of variation and molecular population genetics, from allozymes to DNA polymorphisms, restriction enzymes, PCR and single nucleotide polymorphisms.

Chapter 2: Organization of Genetic Variation

This chapter examines random mating at one locus and several loci and establishes the basic principles for thinking about mathematical models of variation. It develops the Hardy–Weinberg principle, tests for equilibrium, extensions to three or more alleles and X-linked genes, and linkage and linkage disequilibrium, including its causes and the measures D′ and r².

Chapter 3: Random Genetic Drift

Chapter 3 presents the Wright–Fisher model and the diffusion approximation, drift in a subdivided population and effective population size, and then gene trees and coalescence, with coalescent models that include mutation, growth and recombination and applications such as linkage disequilibrium mapping.

Chapter 4: Mutation and the Neutral Theory

Mutation is added to drift. The chapter covers irreversible and reversible mutation, the neutral theory of molecular evolution, the infinite-alleles model (the Ewens sampling formula and the Ewens–Watterson test), the infinite-sites model with Tajima's D and the Fu and Li test, and the relation between mutation and recombination.

Chapter 5: Darwinian Selection

Selection is treated in haploid and diploid organisms, with equilibria (overdominance, heterozygote inferiority), mutation–selection balance and more complex types of selection (frequency-dependent, sexual, kin selection, meiotic drive and epistasis, among others). It closes with interdeme selection and selection in finite populations, including the nearly neutral theory and genetic draft.

Chapter 6: Inbreeding, Population Subdivision, and Migration

The chapter explains the inbreeding coefficient and its genetic effects, population subdivision with Wright's F statistics, the Wahlund principle, assortative mating, migration (the island model, estimates of migration rates) and migration–selection balance, and the inference of population structure from multilocus genotypes.

Chapter 7: Molecular Population Genetics

This is the chapter on sequence-level analysis: the neutral theory, rates of sequence divergence, the molecular clock, patterns of nucleotide and amino acid substitution, the McDonald–Kreitman and HKA tests, gene genealogies, organelle DNA evolution, molecular phylogenetics and multigene families.

Chapter 8: Evolutionary Quantitative Genetics

The chapter moves from single genes to quantitative traits: heritability and resemblance between relatives, artificial selection, genetic models, components of phenotypic variance, covariance among relatives, norm of reaction and genetic correlation, the evolution of quantitative traits and the mapping of QTLs.

Chapter 9: Population Genomics

New in this edition, according to the publisher, the chapter applies population genetic principles at a genome-wide scale: genome size and composition, genome-wide patterns of polymorphism (including hitchhiking versus background selection), differences between species, sexual selection and the sex chromosomes, and transposable elements.

Chapter 10: Human Population Genetics

The last chapter covers human polymorphism and public SNP resources such as the HapMap Project, inferences from SNPs, linkage disequilibrium across the genome, population structure, Mendelian disease, the genetic basis of complex disease risk including genome-wide association studies, signatures of human-specific adaptation and human origins.

Key Concepts

Chapters 1–3: variation, equilibrium and drift

• Hardy–Weinberg principle: the genotype proportions expected under random mating, used as the baseline for later models.
• Linkage disequilibrium: non-random association of alleles at different loci.
• Wright–Fisher model and coalescence: forward and backward descriptions of drift in a finite population.
• Effective population size: the idealised population size that gives the same drift as the real one.

Chapters 4–6: mutation, selection and structure

• Neutral theory: the view that much molecular variation is shaped by mutation and drift.
• Selection and equilibria: balance among selection, mutation and migration.
• Inbreeding coefficient and F statistics: measures of departure from random mating and of population subdivision.

Chapters 7–10: molecular, quantitative, genomic and human applications

• Molecular clock and tests of neutrality: tools such as Tajima's D and the McDonald–Kreitman test for detecting selection in sequence data.
• Heritability: the share of phenotypic variance attributed to genetic differences.
• Hitchhiking and background selection: how selection at one site shapes variation at linked sites.
• Genome-wide association: scanning the genome for variants associated with disease risk.

Critical Analysis

Strengths

• Balance of theory and data. The publisher's description, and a review in The Quarterly Review of Biology by Wolfgang Stephan, stress the balance between theory and observation and between classical and recent data sets and tools.
• Careful build-up. Chapters 2–6 develop the standard models in order: random mating, drift, mutation, selection and structure. Later chapters on molecular data, quantitative traits, genomes and humans reuse them.
• Coalescent theory in the middle of the book. Gene trees and coalescence appear in Chapter 3 and return in Chapters 4, 6 and 7, which reflects the methods that Stephan credits with reshaping the field.
• Problem-solving support. Each chapter ends with a summary and problems, and the volume includes about thirty pages of answers; the publisher adds that worked examples use actual data.

Limitations

• Mathematically demanding. The contents include diffusion approximations, sampling formulae and coalescent models, so readers need comfort with algebra, calculus and probability.
• Dated genomics. Published in 2007, the population genomics and human chapters (for example, the HapMap Project and genome-wide association studies) predate later sequencing projects.
• Length and density. With about 565 pages of main text and dozens of numbered sections, the book is more than a short course covers; instructors must choose among chapters.
• Not a first genetics course. The publisher addresses undergraduate and graduate students and newcomers from other fields, but the models are developed with algebra, calculus and probability, so a prior genetics course is the practical starting point.

Where It Fits in the Course

This is the specialist population genetics text on the genetics list. Slack's Genes: A Very Short Introduction and Thomas's Introducing Genetics: From Mendel to Molecules are gentle starting points, and Griffiths et al.'s Introduction to Genetic Analysis and Snustad and Simmons's Principles of Genetics are standard courses in classical and molecular genetics that supply the prerequisites. Brown's Genomes 5 treats genetics at the level of whole genomes.

Hartl and Clark continue from there to the evolutionary processes that change allele frequencies. Chapter 9 and parts of Chapters 7 and 10 connect with the genome-level material in Brown, but Hartl and Clark's emphasis is on models and statistical inference rather than on genome structure and expression.

How to Use This Book

The book suits advanced undergraduates, graduate students and researchers in evolutionary biology, genetics and human genetics who have completed a genetics course and are comfortable with basic algebra, calculus and probability.

A practical plan:

• Core: Chapters 1–6 in order. They contain the models that everything else uses.
• Next: Chapter 7 for sequence data and tests of neutrality, and Chapter 8 for quantitative traits.
• By interest: Chapter 9 for genome-scale patterns and Chapter 10 for human applications.
• Practice: work the problems at the end of each chapter and check them against the answers section; read the chapter summary first to see what each chapter is for.