Table of Contents

Introduction

Chapter 1. The Molecular Basis of Biology and Evolution
Nucleotide Sequences
Genomes
Genome constituents
Somatic genome processing
DNA Replication
Transcription and Posttranscriptional Modifications of RNA
Genes
Protein-coding genes
RNA-specifying genes
Nontranscribed genes
Pseudogenes
Amino Acids
Proteins
Translation and Genetic Codes
Information Flow among DNA, RNA, and Proteins
Mutation
Classification of mutations
Point Mutations
Segmental Mutations
Recombination
Deletions and insertions
Inversions
Spatial distribution of mutations
Are Mutations Random?

Chapter 2. Allele Dynamics in Populations
Standing Genetic Variation
Gene diversity
Nucleotide diversity
Structural variation
What Is Evolution?
Changes in Allele Frequencies
Selection
Codominance
Dominance and recessiveness
Overdominance and underdominance
Random Genetic Drift
Census Population Size and Effective Population Size
Short-term effective population size
Coalescence and long-term effective population size
Factors conspiring to reduce the effective population size relative to the census population size
Gene Substitution
Fixation probability
Fixation time
Rate of gene substitution
Mutational meltdown: The double jeopardy of small populations
Nearly neutral mutations
Second-Order Selection
The evolution of mutation rates
The evolution of mutational robustness
Violations of Mendel's Laws of Inheritance
Transmission Ratio Distortion
Segregation distortion
Postsegregation distortion
Converting elements
Sex allocation distortion
Autonomous replicating elements
Linkage Equilibrium and Disequilibrium
Hitchhiking and Selective Sweep
Molecular signatures of selective sweeps
The evolution of lactase persistence in Africa and Europe
Background Selection
Epistasis
The Driving Forces in Evolution
The neo-Darwinian theory and the neutral mutation hypothesis
The distribution of fitness effects
A test of neutrality based on genetic polymorphism
Consequences of Explosive Population Growth: Single-Nucleotide Variation in Humans

Chapter 3. DNA and Amino Acid Sequence Evolution
Nucleotide Substitution in a DNA Sequence
Jukes and Cantor's one-parameter model
Kimura's two-parameter model
Number of Nucleotide Substitutions between Two DNA Sequences
Number of substitutions between two noncoding sequences
Substitution schemes with more than two parameters
Violation of assumptions
Saturation
Number of Substitutions between Two Protein-Coding Genes
Number of Amino Acid Replacements between Two Proteins
Alignment of Nucleotide and Amino Acid Sequences
Pairwise alignment
Manual alignment
The dot matrix method
Scoring matrices and gap penalties
Alignment algorithms
Multiple-sequence alignment
Quality of alignments
Alignment of Genomic Sequences

Chapter 4. Rates and Patterns of Molecular Evolution
Rates of Point Mutation
Rates of Segmental Mutations
Rates of Nucleotide Substitution
Rates of substitution in protein-coding sequences
Rates of substitution in noncoding regions
Causes of Variation in Substitution Rates
The concept of functional constraint
Quantifying the degree of protein tolerance toward amino acid replacements
Synonymous versus nonsynonymous rates
Variation among different gene regions
Variation among genes
Variables associated with protein evolutionary rates
Evolutionary conservation and disease
Relaxation of selection
Selective intolerance toward indels
Identifying positive and purifying selection
Estimating the intensity of purifying selection
Are slowly evolving regions always important?
Male-Driven Evolution: Mutational Input and Slow-X Evolution
Rates of Evolution under Positive Selection
Prevalence of positive selection
Fast-X evolution
Rates of Evolution under Balancing Selection
Patterns of Substitution and Replacement
Patterns of spontaneous mutation
Patterns of mutation and strand asymmetry
Clustered multinucleotide substitutions: Positive selection or nonrandomness of mutation?
Patterns of amino acid replacement
What protein properties are conserved in protein evolution?
Heterotachy
Nonrandom Usage of Synonymous Codons
Measures of codon usage bias
Species-specific and universal patterns of codon usage
Determinants of Codon Usage
Interspecific variation in codon usage and amino acid usage
Intragenomic variation in codon usage
Translational efficiency and translation accuracy
The tRNA adaptation index
Intragenic variation in codon usage
Indirect selection on codon usage
Why do only some organisms have biased codon usages?
Codon usage in unicellular and multicellular organisms
Codon usage and population size
Molecular Clocks
Relative Rate Tests
Local Clocks
Nearly equal rates in mice and rats
Lower rates in humans than in monkeys
Higher rates in rodents than in other mammals
Evaluation of the molecular clock hypothesis
"Primitive" versus "advanced": A question of rates
Causes of Variation in Substitution Rates among Evolutionary Lineages
The DNA repair hypothesis
The generation-time effect hypothesis
The metabolic rate hypothesis
The varying-selection hypothesis
Are Living Fossils Molecular Fossils Too?
Phyletic Gradualism, Punctuated Equilibria, and Episodic Molecular Evolution
Rates of Substitution in Organelle DNA
Mitochondrial rates of evolution
Plastid rates of evolution
Substitution and rearrangement rates
Rates of Substitution in Viruses
Human immunodeficiency viruses

Chapter 5. Molecular Phylogenetics and Phylogenetic Trees
Impacts of Molecular Data on Phylogenetic Studies
Advantages of Molecular Data in Phylogenetic Studies
Species and Speciation
The species concept
Speciation
Terminology
Phylogenetic Trees
Rooted and unrooted trees
Scaled and unscaled trees
The Newick format
Number of possible phylogenetic trees
Tree balance
True and inferred trees
Gene trees and species trees
Taxa and clades
Types of Molecular Homology
Types of Data
Character data
Assumptions about character evolution
Polarity and taxonomic distribution of character states
Distance data
Methods of Tree Reconstruction
Distance Matrix Methods
Unweighted pair-group method with arithmetic means (UPGMA)
Sattath and Tversky's neighbors-relation method
Saitou and Nei's neighbor-joining method
Maximum Parsimony Methods
Weighted and unweighted parsimony
Searching for the maximum parsimony tree
Maximum Likelihood Methods
Bayesian Phylogenetics
Topological Comparisons
Topological distance
Consensus trees
Supertrees
Rooting Unrooted Trees
Outgroup rooting
Midpoint rooting
Estimating Branch Lengths
Calibrating Phylogenetic Trees and Estimating Divergence Times
Assessing Tree Reliability
The bootstrap
Tests for two competing trees
Problems Associated with Phylogenetic Reconstruction
Strengths and weaknesses of different methods
Minimizing error in phylogenetic analysis
Genome Trees
Genome trees based on shared gene content
Genome trees from BLASTology
Molecular Phylogenetic Examples
Phylogeny of apes
The utility of polarized character states: Cetartiodactyla and SINE phylogeny
Molecular Phylogenetic Archeology
The disextinction of the quagga
The dusky seaside sparrow: A lesson in conservation biology
Molecular Phylogenetics and the Law
At the Limits of the Tree Metaphor: The Phylogeny of Eukaryotes and the Origin of Organelles
The phylogeny of eukaryotes
Origin of organelles
Phylogenetic Trees as a Means to an End
Parallelism and convergence as signifiers of positive selection
Detecting amino acid sites under positive selection
Reconstructing ancestral proteins and inferring paleoenvironments
Mapping nonmolecular characters onto molecular trees

Chapter 6. Reticulate Evolution and Phylogenetic Networks
Networks
Phylogenetic and Phylogenomic Networks
The median network method
The conditioned-reconstruction method
Inferred reticulations: Are they real?
Examples of Real-Life Phylogenetic Networks
Reticulate evolution by recombination: A resurrected blood-group allele in humans
Speciation by hybridization: The reticulate evolution of woodferns
The Tree of Life Hypothesis
The Vertical and Horizontal Components of Prokaryote Evolution
Prokaryote taxonomy and the meaning of "species" in prokaryotes
The Phylogeny of Everything
The eukaryote-prokaryote divide and the taxonomic validity of Procaryota
The Eubacteria-Archaebacteria divide
The tripartite tree of life and its inadequacy
The Origin of Eukaryotes
The gradual origin hypothesis
The fateful encounter hypothesis
Eukaryotes as an "organizational upgrade"
The nonrandom origin of operational and informational genes in eukaryotes
Why genes in pieces? The origin of the nuclear membrane
All complex life is eukaryotic: The energetics of gene expression
The eukaryotic cell as a one-off innovation and a possible solution to the Fermi paradox
Archaebacterial Systematics: Clade-Specific Archaebacterial Genes and Clade-Specific Horizontal Gene Imports from Eubacteria
The Two Primary Domains of Life
The Public Goods Hypothesis

Chapter 7. Evolution by DNA Duplication
Types of DNA Duplication
Mechanisms of DNA Duplication
Dating Duplications
Gene Duplication and Gene Families
The Prevalence of Gene Duplication
Modes of Evolution of Multigene Families
Divergent Evolution of Duplicated Genes
Nonfunctionalization and gene loss
Nonfunctionalization time
Retention of original function following gene duplication
Evolution of rRNA-specifying genes
Neofunctionalization
Multifunctionality and subfunctionalization
Neosubfunctionalization
Rates of Evolution in Duplicated Genes
Rates and patterns of expression divergence between duplicated genes
Human Globins
Concerted Evolution
Unequal crossing over
Gene conversion
Examples of gene conversion
The relative roles of gene conversion and unequal crossing over
Factors Affecting Concerted Evolution
Number of repeats
Arrangement of repeats
Structure of the repeat unit
Functional requirements and selection
Population size
Evolutionary Implications of Concerted Evolution
Spread of advantageous mutations
Retardation of paralogous gene divergence
Generation of genic variation
Methodological pitfalls due to concerted evolution
Positive selection or biased gene conversion? The curious histories of HAR1 and FXY
Birth-and-Death Evolution
Expansion and contraction of gene families
Examples of birth-and-death evolution
The death of gene families
Mixed Concerted Evolution and Birth-and-Death Evolution
Polysomy
Polyploidy
Diploidization
Distinguishing between gene duplication and genome duplication

Chapter 8. Evolution by Molecular Tinkering
Protein Domains
Internal Gene Duplication
Properties and prevalence of internal gene duplication
Exon-Domain Correspondence
Mosaic Proteins
Exon Shuffling
Phase limitations on exon shuffling
Prevalence of domain shuffling and the evolutionary mobility of protein domains
Domain shuffling and protein-protein interaction networks
Gene Fusion and Fission
Domain Accretion
Strategies of Multidomain Gene Assembly
Evolution by Exonization and Pseudoexonization
Evolution of Overlapping Genes
Alternative Splicing
Sex determination and alternative splicing
Evolution of alternative splicing
Increasing proteome diversity: Alternative splicing or gene duplication?
De Novo Origination of Genes
Nested and Interleaved Genes
Gene Loss and Unitary Pseudogenes: A Molecular Revisiting of the "Law of Use and Disuse"
Functional Convergence
Origin and Evolution of Spliceosomal Introns
A Grand View of Molecular Tinkering: Suboptimality and Gratuitous Complexity
Tinkering in action: The patchwork approach to the evolution of novel metabolic pathways
Irremediable complexity by constructive neutral evolution

Chapter 9. Mobile Elements in Evolution
Mobile Elements, Transposable Elements, and Transposition
Classification of Transposable Elements
Conservative and replicative transposition
DNA- and RNA-mediated transposition
Enzymatic classification of transposable elements
Autonomous and nonautonomous transposable elements
Active and fossil transposable elements
Taxonomic, developmental, and target-site specificity of transposition
DNA-Mediated Transposable Elements
Insertion sequences
Transposons
Nonautonomous DNA-mediated transposable elements
Retroelements
Retrons
TERT genes
Mitochondrial retroplasmids
Group II introns and twintrons
Retrotransposons
Retroviruses
Pararetroviruses
Evolutionary origin of retroelements
Nonautonomous and fossil retrotransposable elements
LINEs and SINEs
SINEs derived from 7SL RNA
SINEs derived from tRNAs and SINEs containing 5S rRNA
SINEs containing snRNA
Mosaic SINEs
Where there's a SINE, there's a LINE
Rate of SINEs evolution
Retrosequences
Retrogenes
Semiprocessed retrogenes
Retropseudogenes
Endogenous non-retroviral fossils
The "Ecology" of Transposable Elements
Transposable elements and the host genome: An evolutionary tug-of-war
Transposable elements and segregation distortion
Evolutionary dynamics of transposable-element copy number
Genetic and Evolutionary Effects of Transposition
Transposable elements as mutagens
Transposable elements and somatic mosaicism
The molecular domestication of transposable elements
Transposition and Speciation
Horizontal Gene Transfer
Telltale signs of horizontal gene transfer
Mechanisms of horizontal gene transfer among prokaryotes
Prevalence and limitations of horizontal gene transfer in prokaryotes
Genomic consequences of gene transfer among prokaryotes
Clinical consequences of gene transfer among prokaryotes
Horizontal Gene Transfer Involving Eukaryotes
Horizontal gene transfer from eukaryotes to prokaryotes
Horizontal gene transfer from prokaryotes to eukaryotes
Horizontal transfer among eukaryotes
Horizontal gene transfer among plants
Horizontal transfer of a functional gene from fungi to aphids
Horizontal transfer of transposable elements among animals
Promiscuous DNA
Transfer of intact functional genes to the nucleus
Transfer of nonfunctional DNA segments from organelles to the nucleus: numts and nupts
Rates and evolutionary impacts of norgDNA insertion

Chapter 10. Prokaryotic Genome Evolution
Genome Size in Prokaryotes
The pangenome, the core genome, and the accessory genome
Increases and decreases in prokaryotic genome sizes
Genome Miniaturization
Genome size reduction in intracellular symbionts and parasites
The miniaturization of organelle genomes
The evolution of mitochondrial genome sizes
The evolution of plastid genome sizes
The Minimal Genome
The comparative genomics approach: Identifying the core genome of all life forms
Probabilistic reconstruction of gene content in the last universal ancestor of life
The experimental gene inactivation approach: Gene essentiality
GC Content in Prokaryotes
Possible explanations for variation in GC content
Chargaff's parity rules
GC Skew and Gene-Density Asymmetries Are Related to DNA Replication Biases
Replichores and chirochores
The location of genes in leading and lagging strands
Chromosomal Evolution in Prokaryotes
Evolution of chromosome number in prokaryotes
Estimating the number of gene order rearrangement events
Gene order evolution
Operon evolution
The Emergence of Alternative Genetic Codes

Chapter 11. Eukaryotic Genome Evolution
Functionality and nonfunctionality in eukaryotic genomes
What is "function" in an evolutionary context?
What do genomes do? An evolutionary classification of genomic function
Changes in functional affiliation
Detecting functionality at the genome level
Phenotypic validation of positive selection
What proportion of the human genome is functional?
How much garbage DNA is in the human genome?
Genome Size, DNA Content, and C Value
Genome size variation and genomic content in eukaryotes
Intraspecific variation in genome size
Mutations That Increase or Decrease Genome Size
The contribution of genome duplication to genome size
The contribution of transposable elements to genome size
Deletions and genome size
Genomic Paradoxes in Eukaryotes
The C-value paradox
Possible solutions to the C-value paradox
Why so much of the genome is transcribed--or is it?
Life History and Cellular Correlates of Genome Size
The nucleocytoplasmic ratio
The coincidence hypothesis
Nucleotypic hypotheses
The nucleoskeletal hypothesis
Is small genome size an adaptation to flight?
The C-Value Paradox: The Neutralist Hypothesis
Selfish DNA
The mutational hazard hypothesis
Is it junk DNA or is it indifferent DNA?
Trends in Genome Size Evolution
Is there an upper limit to genome size?
Genome miniaturization in eukaryotes
Protein-Coding Gene Number Variation and the G-Value Paradox
Possible solutions to the G-value paradox
The I value
Gene Number Evolution
Methodologies for Studying Gene Repertoire Evolution
Gene-family cluster analysis
Functional clustering of proteins
Supervised machine learning and the subcellular localization of proteins
Gene ontology
Chromosome Number and Structure
Chromosome number variation
Chromosome morphology and chromosome types
Chromosome size variation
Euchromatin and heterochromatin
Chromosomal Evolution
Chromosome number evolution
Chromosomal rearrangements
Evolutionary patterns of chromosomal rearrangements
Is gene order conserved?
Gene Distribution Between and Within Chromosomes
Gene density
Do genes cluster by function?
The Repetitive Structure of the Eukaryotic Genome
Tandemly repeated sequences
Mutational processes affecting repeat-unit number in tandemly repeated DNA
The contribution of tandem repeats to genome size
Do tandemly repeated DNA sequences have a function?
Centromeres as examples of indifferent DNA
Genome Compositional Architecture
Segmentation algorithms and compositional domains
Compositional architectures of mammalian nuclear genomes
The origin and evolution of compositional domains

Chapter 12. The Evolution of Gene Regulation, by Amy K. Sater
Pretranscriptional Regulation
Regulation by covalent modifications of histones
DNA methylation
Regulation at the Transcriptional Level
Promoters
Promoter evolution
Divergent transcription
Enhancers
Shadow enhancers
Insulators
Posttranscriptional Regulation
RNA interference
Patterns of evolution of miRNAs
Do miRNAs have a deep evolutionary history?
Does translational regulation contribute to phenotypic evolution?

Chapter 13. Experimental Molecular Evolution, by Tim F. Cooper
What Is Experimental Evolution?
The basic design of evolutionary experiments
How to measure fitness and changes in fitness in evolutionary experiments
The Contribution of Experimental Evolution to Evolutionary Biology
Population divergence and the adaptive landscape metaphor
Historical contingency
Epistasis
Mutation Dynamics
Neutral mutation rates
Non-neutral mutation rates
Targets of Selection

Literature Cited
Index

About the Author

Dan Graur is John and Rebecca Moores Professor in the Department of Biology and Biochemistry at the University of Houston and Professor Emeritus of Zoology at Tel Aviv University, Israel.

Reviews

"Importantly, this book goes beyond an overview of the current status of the field. By explaining the fundamental concepts of population genetics, which is essential to understanding molecular evolution, Graur gives his readers the necessary tools for a critical analysis of the different topics covered by his volume. Readers afraid of mathematical formulas should not be discouraged by the equations present throughout the book, as the mathematical concepts are
clearly explained and illustrated. . . . This book is a must read for anyone lacking the molecular evolution background necessary to make sense of the current deluge of molecular data and, more
generally, for anyone trying to keep up to date with the fast moving field of molecular and genome evolution." - Jean-Francois Gout, The Quarterly Review of Biology