Table Of ContentMutation-Driven
Evolution
Masatoshi Nei
Pennsylvania State University
1
Mutation-Driven Evalution. First Edition. Masatoshi Nei.
© Masatoshi Nei 2013. Published 2013 by Oxford University Press.
3
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Contents
Preface ix
1 Selectionism and Mutationism 1
1.1 Darwin’s Theory of Evolution 1
1.2 Criticisms of Darwin’s Theory 2
1.3 Evolution by Discontinuous Variation 3
1.4 Mutationism 6
1.5 Neo-Darwinism 7
1.6 Neomutationism or Mutation-Driven Evolution 9
1.7 Survival of the Fittest and Survival of the Niche-Filling Variants 9
2 Neo-Darwinism and Panselectionism 1 3
2.1 Backgrounds 13
2.2 Allele Frequency Changes as the Basic Process of Evolution 14
Mutation 14
Natural Selection with Constant Fitness 15
Mutation-Selection Balance 17
Balanced Polymorphism 18
Natural Selection for Multiple Loci 19
2.3 Diffi culties of Defi ning and Estimating Selection Coeffi cients 20
Estimates of Selection Coeffi cients and their Reliability 20
Fluctuation of Selection Coeffi cients 22
General Considerations 23
2.4 Stochastic Changes of Allele Frequencies 24
Probability of Fixation of Mutant Alleles 25
Equilibrium Distribution of Allele Frequencies 25
Effective Population Size and Sampling Errors of Allele Frequencies 28
Random Errors Caused by Fluctuation of Selection Coeffi cients 29
2.5 Mutation and Standing Genetic Variation 31
Artifi cial and Natural Selection in Quantitative Characters 31
Evolution of Drug Resistance 34
2.6 Classical and Balance Theories of Maintenance of Genetic Variation 34
Genetic Load 35
Number of Alleles that can be Maintained in Finite Populations 36
2.7 Natural Selection as a Creative Force 37
2.8 Summary 39
iii
iv CONTENTS
3 E volutionary Theories in the Neo-Darwinian Era 41
3.1 Modifi er Genes 41
Evolution of Dominance 42
Modifi cation of Linkage Intensity 43
3.2 Fisher’s Fundamental Theorem of Natural Selection 44
3.3 Cost of Natural Selection and Fertility Excess Required 46
3.4 Shifting Balance Theory of Evolution 48
3.5 Accumulation of Nonfunctional and Deleterious Mutations 50
Y Chromosomes 50
Nonfunctional Mutations in Duplicate Genes 52
Deleterious Mutations and Muller’s Ratchet 52
3.6 Bottleneck Effects and Genetic Variability 53
3.7 Beanbag Genetics and Evolution 56
3.8 Summary 58
4 Molecular Evolution 5 9
4.1 Early Studies of Molecular Evolution 59
4.2 Neutral Evolution at the Protein Level 60
Cost of Natural Selection and Neutral Theory 60
Defi nition of Neutral Mutations 61
King and Jukes’s View 63
Defi nition of Neutral Theory 64
4.3 Molecular Clocks 65
Evolutionary Rate under Purifying Selection 65
Evolutionary Rate and Generation Time 65
Functional Constraints of Proteins 66
Variation in Mutation Rate 67
Molecular Clocks and Neutral Theory 68
4.4 Evolution of Protein-Coding Genes 69
General Properties of Evolution of Protein-Coding Genes 69
Fast-Evolving Genes 70
4.5 Protein Polymorphism 70
4.6 Neutral Evolution at the DNA Level 72
Synonymous and Nonsynonymous Nucleotide Substitutions 72
Pseudogenes as a Paradigm of Neutral Evolution 72
Slightly Deleterious or Nearly Neutral Mutations 73
4.7 Advantageous Mutations 74
Evolution of New Protein Function 74
Immune System Genes 78
Trans-Species Polymorphism 79
4.8 Recent Statistical Studies for Detecting Positive Selection 81
Bayesian Methods for Identifying Positively-Selected Codon Sites 81
MK Test and its Extensions 82
Extended Haplotype Homozygosity and F Tests 84
ST
Statistical Studies and Biochemical Verifi cation 86
Frequency Distributions of Mutant Nucleotides 87
4.9 Summary 87
CONTENTS v
5 Gene Duplication, Multigene Families, and Repetitive DNA Sequences 89
5.1 New Genes Generated by Gene Duplication 89
Increase in the Number of Genes by Gene Duplication 90
Genome Size and Number of Genes 91
Gene Numbers and Phenotypic Complexity 92
5.2 Evolution of Multigene Families 94
5.3 Concerted Evolution 95
Unequal Crossover, Gene Conversion, and Purifying Selection 95
Tandemly Arrayed Histone Genes 96
5.4 Birth-and-Death Evolution 97
MHC Genes 97
Immunoglobulins and other Immune Systems Genes 99
Olfactory and other Chemosensory Receptor Genes 101
Birth-and-Death Evolution with Strong Purifying Selection 102
5.5 Multigene Families and Evolution of New Genetic Systems 103
Adaptive Immune System 103
Homeobox Genes Involved in Animal and Plant Development 104
Multigene Families and Flower Development in Plants 105
5.6 Genomic Drift and Copy Number Variation 105
5.7 Noncoding DNA and Transposable Genetic Elements 107
Exons and Introns 108
Transposable Genetic Elements 109
Tandem Repetitive Sequences 110
5.8 Summary 110
6 Evolution of Phenotypic Characters 113
6.1 Changing Concepts of the Gene and Gene Expression 113
Defi nition of a Gene 113
Protein-Coding and Regulatory Regions of Genes 115
Gene Regulatory Networks 116
Small RNAs that Control the Level of Gene Expression 116
Methylation and Epigenetics 117
Signaling Pathways and Gene Interaction 118
6.2 Evolution of Physiological and Morphological Characters 120
Changes in the Protein-Coding Regions of Genes 120
Gene Regulation Hypothesis 122
Major Gene Effect Hypothesis 126
Gene Regulatory Networks and Morphological Evolution 128
6.3 Evolution of Gene Regulatory Systems 129
Cis-Regulatory Elements 129
E volutionary Change of MicroRNAs and other Small RNAs
Controlling Gene Expression 130
6.4 Epigenetics and Phenotypic Evolution 131
Environmental Sex Determination 131
Evolution of Temperature-Dependent Sex Determination 132
Vernalization and Flowering in Plants 132
vi CONTENTS
6.5 Gene Co-Option and Horizontal Gene Transfer 133
Gene Co-Option 133
Horizontal Gene Transfer 134
Photosynthetic Animals 135
6.6 Summary 136
7 Mutation and Selection in Speciation 137
7.1 Speciation by Chromosomal Mutations 138
Formation of New Species by Polyploidization 138
Changes of Genomic Structures and Speciation 139
Chromosomal Rearrangements and Speciation 140
7.2 Evolution of Reproductive Isolation by Genic Mutation 141
Oka Model of Speciation by Duplicate Gene Mutations 141
Dobzhansky-Muller (DM) Model of Evolution of Reproductive Isolation 143
Multiallelic Complementary Genes Model 146
Single-Locus Speciation 148
7.3 Reproductive Isolation by Complex Genetic Systems 149
Segregation Distorters and Speciation 149
Heterochromatin-Associated Hybrid Incapacity 150
7.4 Other Mechanisms of Evolution of Reproductive Isolation 150
7.5 Speciation by Bottleneck Effects 151
7.6 Hybrid Sterility Generated by Passive Process of Phenotypic Evolution 152
7.7 Summary 153
8 Adaptation and Evolution 155
8.1 Adaptation by Mutation 155
8.2 Evolution of Some Specifi c Characters 156
Evolution of Eyes and Photoreceptors 156
Evolution of Caste Systems in Honeybees and some other Insects 157
Evolution of Asymmetric Morphology in Flatfi sh, Snails, and other
Organisms 161
8.3 Regressive Evolution and Pseudogenes 162
Universality of Vestigial Characters 162
Molecular Basis of Regressive Evolution 162
Parasitic Organisms and their Genomic Changes 165
8.4 Evolution of Sex-Determination Mechanisms 166
Sex Determination in Vertebrates 167
Sex Determination in Invertebrates 169
8.5 Degeneration of the Y (W) Chromosome 171
Y Degeneration and Dosage Compensation 171
Molecular Basis of X-Chromosome Dosage Compensation 172
Evolution by Sexually Antagonistic Mutations 173
8.6 Evolution of Behavioral Characters 174
Selfi sh Gene Theory of Evolution 174
Molecular Studies of Behavioral Genes 175
8.7 Summary 177
CONTENTS vii
9 Mutation and Selection in Evolution 179
9.1 Distinct Processes of Mutation and Selection 179
9.2 Random Factors and Gene Co-Option in Evolution 181
9.3 Retrospective and Prospective Studies of Evolution 182
9.4 Genomic Constraints and Constraint-Breaking Evolution 183
Progressive Evolution 183
Origin of Life Without Purpose 183
Constraint-Breaking Evolution 184
9.5 Genetic Variation within Species 185
9.6 Niche-Filling Evolution 186
10 General Summary and Conclusion 189
Appendix: Mathematical Notes 201
A. Allele Frequency Changes Due to Natural Selection 201
Deterministic Models for Allele Frequency Changes 201
Equilibrium Frequencies Due to Mutation and Selection 201
B. Allele Frequency Distributions under the Infi nite-Site Model 202
C. Temporal Fluctuation of Selection Coeffi cients 202
General Comments 202
D. Artifi cial Selection for Quantitative Characters 203
E. Genetic Load 203
Mutation Load 204
Segregation Load 204
F. Bayesian Method of Detecting Positively Selected Codons 204
References 207
Author Index 233
Subject Index 238
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Preface
I started my career with theoretical population approach of studying evolution was integrated with
genetics in the 1960s after a short period of fi eld population genetics theory in the latter half of the
work experience concerning quantitative genetics. 1960s and in the 1970s. This integration transformed
At that time evolutionary studies were conducted the study of evolution profoundly. First, we could
primarily by comparing phenotypic characters now identify homologous genes in different species
among individuals within and between species. and study long-term evolution of genes by compar-
These studies did not give clear insights into the ing the nucleotide or amino acid sequences from
cause and the effect of evolution, because the genetic different species. Second, molecular data on the
basis of phenotypic characters was not well evolutionary change of genes soon indicated the
understood. importance of mutation in evolution. Third, com-
In theoretical population genetics, we could con- parison of the DNA contents of different species
sider a set of alleles at one or a few loci and study suggested that gene or genome duplication occurred
the theoretical changes of genotype frequencies due frequently in the process of evolution. Because gene
to mutation, natural selection, and genetic drift. or genome duplication is a form of mutation in the
These studies gave only possible evolutionary broad sense, I realized that mutation is the driving
changes of populations, but they were still much force of evolution. Yet, this view was regarded as a
better than intuitive arguments. For this reason, a heresy at the time when neo-Darwinism dominated
large body of mathematical theories of evolution the fi eld. In the meantime the neutral theory of
was developed. These theories depended on many molecular evolution was proposed to explain the
simplifying assumptions about the breeding sys- evolution of genes and proteins. This theory clearly
tem, population structure, selection coeffi cients, showed that the evolution of nucleotide sequences
gene interaction, etc., and different assumptions has occurred mainly by random fi xation of neutral
about these factors often generated very different mutations. However, most neo-Darwinians did not
predictions of evolutionary changes. This resulted pay much attention to this discovery, because they
in many controversies which could not be resolved believed that neutral evolution has nothing to do
easily because of the diffi culty of doing experimen- with phenotypic evolution, in which most evolu-
tal studies. At that time, population genetics was tionists are interested. In fact, even the proponents
dominated by neo-Darwinism with the idea of per- of the neutral theory of molecular evolution stated
vasive natural selection, and I was working within that phenotypic evolution occurs mostly by natural
the framework of neo-Darwinism. Furthermore, selection, as will be mentioned later.
because it was diffi cult to identify the homologous By the early 1970s, I came to believe that the prin-
genes between different species, population genet- ciple of phenotypic evolution must be the same as
ics studies were primarily concerned with the gene that of molecular evolution because both types of
frequency changes within species. evolution are controlled by mutation at the DNA
In the early 1960s a number of molecular biolo- level. I briefl y presented this idea in my 1975 book
gists were working on the evolutionary changes of Molecular Population Genetics and Evolution . However,
genes and proteins at the molecular level, and this few people paid attention to this view. I elaborated
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