The neutral theory of molecular evolution in the genomic era.

The neutral theory of molecular evolution has been widely accepted and is the guiding principle for studying evolutionary genomics and the molecular basis of phenotypic evolution. Recent data on genomic evolution are generally consistent with the neutral theory. However, many recently published papers claim the detection of positive Darwinian selection via the use of new statistical methods. Examination of these methods has shown that their theoretical bases are not well established and often result in high rates of false-positive and false-negative results. When the deficiencies of these statistical methods are rectified, the results become largely consistent with the neutral theory. At present, genome-wide analyses of natural selection consist of collections of single-locus analyses. However, because phenotypic evolution is controlled by the interaction of many genes, the study of natural selection ought to take such interactions into account. Experimental studies of evolution will also be crucial.

[1]  Austin L. Hughes,et al.  Codon-based tests of positive selection, branch lengths, and the evolution of mammalian immune system genes , 2008, Immunogenetics.

[2]  R. Lewontin,et al.  INTERACTION BETWEEN INVERSION POLYMORPHISMS OF TWO CHROMOSOME PAIRS IN THE GRASSHOPPER, MORABA SCURRA. , 1960 .

[3]  R. Hudson,et al.  A test of neutral molecular evolution based on nucleotide data. , 1987, Genetics.

[4]  Adam Eyre-Walker,et al.  Changing effective population size and the McDonald-Kreitman test. , 2002, Genetics.

[5]  Carlos D Bustamante,et al.  Localizing Recent Adaptive Evolution in the Human Genome , 2007, PLoS genetics.

[6]  W. Li,et al.  Evidence for higher rates of nucleotide substitution in rodents than in man. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[7]  S. Easteal,et al.  Generation time and the rate of molecular evolution. , 1985, Molecular biology and evolution.

[8]  D. Kohne Evolution of higher-organism DNA , 1970, Quarterly Reviews of Biophysics.

[9]  R. Nielsen Molecular signatures of natural selection. , 2005, Annual review of genetics.

[10]  R. Axel,et al.  A novel multigene family may encode odorant receptors: A molecular basis for odor recognition , 1991, Cell.

[11]  Joshua M Akey,et al.  Where do we go from here? Constructing genomic maps of positive selection in humans: , 2009 .

[12]  M. Steiper,et al.  Age at first reproduction explains rate variation in the strepsirrhine molecular clock , 2009, Proceedings of the National Academy of Sciences.

[13]  M. Beaumont,et al.  Evaluating loci for use in the genetic analysis of population structure , 1996, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[14]  F. Ayala,et al.  On the virtues and pitfalls of the molecular evolutionary clock. , 1986, The Journal of heredity.

[15]  L. Duret,et al.  Pervasive positive selection on duplicated and nonduplicated vertebrate protein coding genes. , 2008, Genome research.

[16]  S. Gammeltoft,et al.  Coypu insulin. Primary structure, conformation and biological properties of a hystricomorph rodent insulin. , 1986, Biochemical Journal.

[17]  Sudhir Kumar,et al.  The timetree of life , 2009 .

[18]  M. Jakobsson,et al.  Nonlinear Dynamics of Nonsynonymous (dN) and Synonymous (dS) Substitution Rates Affects Inference of Selection , 2009, Genome biology and evolution.

[19]  S. Muse,et al.  A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome. , 1994, Molecular biology and evolution.

[20]  A. Robertson Gene frequency distributions as a test of selective neutrality. , 1975, Genetics.

[21]  M. Shriver,et al.  Interrogating a high-density SNP map for signatures of natural selection. , 2002, Genome research.

[22]  L. Katz,et al.  Dramatic diversity of ciliate histone H4 genes revealed by comparisons of patterns of substitutions and paralog divergences among eukaryotes. , 2004, Molecular biology and evolution.

[23]  Jianzhi Zhang Parallel adaptive origins of digestive RNases in Asian and African leaf monkeys , 2006, Nature Genetics.

[24]  Gillespie,et al.  Development of Neutral and Nearly Neutral Theories , 1996, Theoretical population biology.

[25]  S. Ohno,et al.  So much "junk" DNA in our genome. , 1972, Brookhaven symposia in biology.

[26]  H. Akashi,et al.  Inferring weak selection from patterns of polymorphism and divergence at "silent" sites in Drosophila DNA. , 1995, Genetics.

[27]  M. Nei,et al.  EFFECTS OF RANDOM FLUCTUATION OF SELECTION INTENSITY ON GENETIC VARIABILITY IN A FINITE POPULATION , 1976 .

[28]  T. Ohta Fixation probability of a mutant influenced by random fluctuation of selection intensity. , 1972 .

[29]  Olivier Fedrigo,et al.  Promoter regions of many neural- and nutrition-related genes have experienced positive selection during human evolution , 2007, Nature Genetics.

[30]  M. Lynch Mutation accumulation in transfer RNAs: molecular evidence for Muller's ratchet in mitochondrial genomes. , 1996, Molecular biology and evolution.

[31]  Richard E. Dickerson,et al.  The structure of cytochromec and the rates of molecular evolution , 2005, Journal of Molecular Evolution.

[32]  J. Hermisson Who believes in whole-genome scans for selection? , 2009, Heredity.

[33]  Huan Zhang,et al.  Elucidation of phenotypic adaptations: Molecular analyses of dim-light vision proteins in vertebrates , 2008, Proceedings of the National Academy of Sciences.

[34]  T. Ohta,et al.  The Average Number of Generations until Fixation of a Mutant Gene in a Finite Population. , 1969, Genetics.

[35]  David Haussler,et al.  Forces Shaping the Fastest Evolving Regions in the Human Genome , 2006, PLoS genetics.

[36]  A. Yoshida,et al.  The Role of Mutations in Evolution , 1965 .

[37]  H. Muller Advances in radiation mutagenesis through studies on Drosophila. , 1959, Biological sciences.

[38]  W. Fitch Toward Defining the Course of Evolution: Minimum Change for a Specific Tree Topology , 1971 .

[39]  M. Perutz Species adaptation in a protein molecule. , 1983, Molecular biology and evolution.

[40]  H. Matsunami,et al.  Dynamic functional evolution of an odorant receptor for sex-steroid-derived odors in primates , 2009, Proceedings of the National Academy of Sciences.

[41]  Adam Eyre-Walker,et al.  Adaptive protein evolution in Drosophila , 2002, Nature.

[42]  Response to Yang et al.: Problems with Bayesian methods of detecting positive selection at the DNA sequence level , 2009, Proceedings of the National Academy of Sciences.

[43]  M. Nei The new mutation theory of phenotypic evolution , 2007, Proceedings of the National Academy of Sciences.

[44]  M. Nei,et al.  Extent of protein polymosphism and the neutral mutation theory , 1984 .

[45]  Ziheng Yang PAML 4: phylogenetic analysis by maximum likelihood. , 2007, Molecular biology and evolution.

[46]  Matthew W. Hahn,et al.  Toward a Selection Theory of Molecular Evolution , 2008, Evolution; international journal of organic evolution.

[47]  G. Simpson ORGANISMS AND MOLECULES IN EVOLUTION. , 1964, Science.

[48]  Masatoshi Nei,et al.  Genomic drift and copy number variation of sensory receptor genes in humans , 2007, Proceedings of the National Academy of Sciences.

[49]  J. Haldane The estimation of viabilities , 1956, Journal of Genetics.

[50]  E. Mayr What Evolution Is , 2001 .

[51]  A. Novick,et al.  Experiments with the Chemostat on spontaneous mutations of bacteria. , 1950, Proceedings of the National Academy of Sciences of the United States of America.

[52]  M. Kimura,et al.  The rate of molecular evolution considered from the standpoint of population genetics. , 1969, Proceedings of the National Academy of Sciences of the United States of America.

[53]  M. Nei Molecular Evolutionary Genetics , 1987 .

[54]  R. A. Fisher,et al.  The Genetical Theory of Natural Selection , 1931 .

[55]  T. Ohta Near-neutrality in evolution of genes and gene regulation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[56]  Zhaohui S. Qin,et al.  Genome-wide detection and characterization of positive selection in human populations , 2007 .

[57]  Damian Smedley,et al.  BioMart – biological queries made easy , 2009, BMC Genomics.

[58]  Wen-Hsiung Li,et al.  Rates of nucleotide substitution vary greatly among plant mitochondrial, chloroplast, and nuclear DNAs. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[59]  Pardis C Sabeti,et al.  Positive Natural Selection in the Human Lineage , 2006, Science.

[60]  L. Pauling,et al.  Evolutionary Divergence and Convergence in Proteins , 1965 .

[61]  A. Eyre-Walker,et al.  The Distribution of Fitness Effects of New Deleterious Amino Acid Mutations in Humans , 2006, Genetics.

[62]  Colin N. Dewey,et al.  Initial sequencing and comparative analysis of the mouse genome. , 2002 .

[63]  T. Miyata,et al.  Rapidly evolving mouse alpha-globin-related pseudo gene and its evolutionary history. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[64]  Masatoshi Nei,et al.  Selectionism and neutralism in molecular evolution. , 2005, Molecular biology and evolution.

[65]  Chenhui Zhang,et al.  Adaptive genic evolution in the Drosophila genomes , 2007, Proceedings of the National Academy of Sciences.

[66]  Pierre Baldi,et al.  Global landscape of recent inferred Darwinian selection for Homo sapiens , 2006, Proc. Natl. Acad. Sci. USA.

[67]  Ziheng Yang,et al.  Statistical methods for detecting molecular adaptation , 2000, Trends in Ecology & Evolution.

[68]  J. Klein,et al.  Evolution of the major histocompatibility complex. , 1986, Critical reviews in immunology.

[69]  D. Petrov,et al.  Pervasive Natural Selection in the Drosophila Genome? , 2009, PLoS genetics.

[70]  P. Green,et al.  Bayesian Markov chain Monte Carlo sequence analysis reveals varying neutral substitution patterns in mammalian evolution. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[71]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[72]  Joanna L. Kelley,et al.  Positive selection in the human genome: from genome scans to biological significance. , 2008, Annual review of genomics and human genetics.

[73]  A. Eyre-Walker,et al.  The genomic rate of adaptive amino acid substitution in Drosophila. , 2004, Molecular biology and evolution.

[74]  Joshua M Akey,et al.  Genomic signatures of positive selection in humans and the limits of outlier approaches. , 2006, Genome research.

[75]  Sergei L. Kosakovsky Pond,et al.  HyPhy: hypothesis testing using phylogenies , 2005, Bioinform..

[76]  E. Margoliash PRIMARY STRUCTURE AND EVOLUTION OF CYTOCHROME C. , 1963, Proceedings of the National Academy of Sciences of the United States of America.

[77]  R. Milkman Roger Milkman - selection is the major determinant , 1976 .

[78]  E. Mayr,et al.  The objects of selection. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[79]  M. Nei,et al.  Lewontin-Krakauer test for neutral genes , 1975 .

[80]  C. Meiklejohn,et al.  Positive and negative selection on the mitochondrial genome. , 2007, Trends in genetics : TIG.

[81]  Doron Lancet,et al.  Natural selection on the olfactory receptor gene family in humans and chimpanzees. , 2003, American journal of human genetics.

[82]  C. Müller,et al.  The Mammalian Molecular Clockwork Controls Rhythmic Expression of Its Own Input Pathway Components , 2009, The Journal of Neuroscience.

[83]  Jianzhi Zhang,et al.  More genes underwent positive selection in chimpanzee evolution than in human evolution , 2007, Proceedings of the National Academy of Sciences.

[84]  A. Hughes,et al.  Synonymous and nonsynonymous polymorphisms versus divergences in bacterial genomes. , 2008, Molecular biology and evolution.

[85]  J. Akey,et al.  Adaptive evolution in humans revealed by the negative correlation between the polymorphism and fixation phases of evolution , 2007, Proceedings of the National Academy of Sciences.

[86]  P. Boursot,et al.  Interpretation of variation across marker loci as evidence of selection. , 2001, Genetics.

[87]  R. Doolittle,et al.  Amino-Acid Sequence Investigations of Fibrinopeptides from Various Mammals: Evolutionary Implications , 1964, Nature.

[88]  R. Lewontin,et al.  Distribution of gene frequency as a test of the theory of the selective neutrality of polymorphisms. , 1973, Genetics.

[89]  Wen-Hsiung Li,et al.  An evaluation of the molecular clock hypothesis using mammalian DNA sequences , 2007, Journal of Molecular Evolution.

[90]  M. Nei,et al.  Pseudogenes as a paradigm of neutral evolution , 1981, Nature.

[91]  A. Robertson Letters to the editors: Remarks on the Lewontin-Krakauer test. , 1975, Genetics.

[92]  S. Pääbo,et al.  Accelerated Evolution of Conserved Noncoding Sequences in Humans , 2006, Science.

[93]  David L Stern,et al.  The Loci of Evolution: How Predictable is Genetic Evolution? , 2008, Evolution; international journal of organic evolution.

[94]  Masatoshi Nei,et al.  Origins and evolution of the recA/RAD51 gene family: Evidence for ancient gene duplication and endosymbiotic gene transfer , 2006, Proceedings of the National Academy of Sciences.

[95]  Ryan D. Hernandez,et al.  Natural selection on protein-coding genes in the human genome , 2005, Nature.

[96]  M. Stoneking,et al.  Identification and Analysis of Genomic Regions with Large Between‐Population Differentiation in Humans , 2007, Annals of human genetics.

[97]  Robert K. Moyzis,et al.  Recent acceleration of human adaptive evolution , 2007, Proceedings of the National Academy of Sciences.

[98]  A. Porter A test for deviation from island‐model population structure , 2003, Molecular ecology.

[99]  S. Wright,et al.  Evolution in Mendelian Populations. , 1931, Genetics.

[100]  F. Tajima Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. , 1989, Genetics.

[101]  G. Cochran,et al.  A genetic legacy from archaic Homo. , 2008, Trends in genetics : TIG.

[102]  William J. Sutherland,et al.  Natural Selection in the Wild. , 1987 .

[103]  John Parsch,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:Prevalence of positive selection among nearly neutral amino acid replacements in Drosophila , 2007 .

[104]  A. Eyre-Walker,et al.  The rate of adaptive evolution in enteric bacteria. , 2006, Molecular biology and evolution.

[105]  S. Carroll Evo-Devo and an Expanding Evolutionary Synthesis: A Genetic Theory of Morphological Evolution , 2008, Cell.

[106]  Bruce T Lahn,et al.  Positive selection on the human genome. , 2004, Human molecular genetics.

[107]  M. Nei,et al.  Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection , 1988, Nature.

[108]  L. Excoffier,et al.  Detecting loci under selection in a hierarchically structured population , 2009, Heredity.

[109]  Masatoshi Nei,et al.  The evolution of animal chemosensory receptor gene repertoires: roles of chance and necessity , 2008, Nature Reviews Genetics.

[110]  T J White,et al.  Biochemical evolution. , 1977, Annual review of biochemistry.

[111]  A. Robertson Remarks on the Lewontin-Krakauer test , 1975 .

[112]  H. Muller,et al.  Our load of mutations. , 1950, American journal of human genetics.

[113]  Philip C. J. Donoghue,et al.  Calibrating and constraining molecular clocks , 2009 .

[114]  Liqing Zhang,et al.  Human SNPs reveal no evidence of frequent positive selection. , 2005, Molecular biology and evolution.

[115]  Nicolas Galtier,et al.  Population Size Does Not Influence Mitochondrial Genetic Diversity in Animals , 2006, Science.

[116]  M. Hurles,et al.  Fast-evolving noncoding sequences in the human genome , 2007, Genome Biology.

[117]  M. Adams,et al.  Inferring Nonneutral Evolution from Human-Chimp-Mouse Orthologous Gene Trios , 2003, Science.

[118]  C. Laird,et al.  Rate of Fixation of Nucleotide Substitutions in Evolution , 1969, Nature.

[119]  Colin N. Dewey,et al.  Population Genomics: Whole-Genome Analysis of Polymorphism and Divergence in Drosophila simulans , 2007, PLoS biology.

[120]  F. Melo,et al.  Adaptive evolution of the insulin gene in caviomorph rodents. , 2005, Molecular biology and evolution.

[121]  Masatoshi Nei,et al.  Reliabilities of identifying positive selection by the branch-site and the site-prediction methods , 2009, Proceedings of the National Academy of Sciences.

[122]  E. Davidson The Regulatory Genome: Gene Regulatory Networks In Development And Evolution , 2006 .

[123]  R. DeSalle,et al.  Adaptive Evolution of Genes and Genomes , 2000, Heredity.

[124]  M. Kimura Evolutionary Rate at the Molecular Level , 1968, Nature.

[125]  David N. Messina,et al.  Evolutionary and Biomedical Insights from the Rhesus Macaque Genome , 2007, Science.

[126]  S. Yokoyama Evolution of dim-light and color vision pigments. , 2008, Annual review of genomics and human genetics.

[127]  Sewall Wright,et al.  ON THE ROLES OF DIRECTED AND RANDOM CHANGES IN GENE FREQUENCY IN THE GENETICS OF POPULATIONS , 1948, Evolution; international journal of organic evolution.

[128]  J. Pritchard,et al.  A Map of Recent Positive Selection in the Human Genome , 2006, PLoS biology.

[129]  B. Gaut,et al.  Molecular population genetics and the search for adaptive evolution in plants. , 2005, Molecular biology and evolution.

[130]  R. Lewontin,et al.  Testing the Heterogeneity of F Values , 1975 .

[131]  P. Andolfatto Adaptive evolution of non-coding DNA in Drosophila , 2005, Nature.

[132]  A. Clark,et al.  Recent and ongoing selection in the human genome , 2007, Nature Reviews Genetics.

[133]  Mutational pressure as the main cause of molecular evolution and polymorphism. , 1974, Nature.

[134]  Steven A. Benner,et al.  Reconstructing the evolutionary history of the artiodactyl ribonuclease superfamily , 1995, Nature.

[135]  M. Nei,et al.  Positive Darwinian selection after gene duplication in primate ribonuclease genes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[136]  M. Nei,et al.  MOLECULAR POPULATION GENETICS AND EVOLUTION , 1976 .

[137]  M. Nordborg,et al.  Selection on amino acid substitutions in Arabidopsis. , 2008, Molecular biology and evolution.

[138]  Justin C. Fay,et al.  A Catalog of Neutral and Deleterious Polymorphism in Yeast , 2008, PLoS genetics.

[139]  Joseph K. Pickrell,et al.  Signals of recent positive selection in a worldwide sample of human populations. , 2009, Genome research.

[140]  M. Kimura,et al.  The neutral theory of molecular evolution. , 1983, Scientific American.

[141]  Justin C. Fay,et al.  Testing the neutral theory of molecular evolution with genomic data from Drosophila , 2002, Nature.

[142]  Deborah A Nickerson,et al.  Genomic regions exhibiting positive selection identified from dense genotype data. , 2005, Genome research.

[143]  Masatoshi Nei,et al.  Simulation study of the reliability and robustness of the statistical methods for detecting positive selection at single amino acid sites. , 2002, Molecular biology and evolution.

[144]  Jeffrey P. Mower,et al.  Extensive variation in synonymous substitution rates in mitochondrial genes of seed plants , 2007, BMC Evolutionary Biology.

[145]  R. Horuk,et al.  Evolutionary change in the insulin receptors of hystricomorph rodents , 1979, Nature.

[146]  Sudhir Kumar,et al.  Genomic clocks and evolutionary timescales. , 2003, Trends in genetics : TIG.

[147]  N. Goldman,et al.  A codon-based model of nucleotide substitution for protein-coding DNA sequences. , 1994, Molecular biology and evolution.

[148]  L. Quintana-Murci,et al.  Natural selection has driven population differentiation in modern humans , 2008, Nature Genetics.

[149]  Yasuhiro Go,et al.  Similar numbers but different repertoires of olfactory receptor genes in humans and chimpanzees. , 2008, Molecular biology and evolution.

[150]  D. Wildman,et al.  Distinct genomic signatures of adaptation in pre- and postnatal environments during human evolution , 2008, Proceedings of the National Academy of Sciences.

[151]  M. Kreitman,et al.  Adaptive protein evolution at the Adh locus in Drosophila , 1991, Nature.

[152]  Xiaoquan Wen,et al.  Correction: A Map of Recent Positive Selection in the Human Genome , 2006, PLoS Biology.

[153]  J. Klein,et al.  Intensity of natural selection at the major histocompatibility complex loci. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[154]  O. Gaggiotti,et al.  A Genome-Scan Method to Identify Selected Loci Appropriate for Both Dominant and Codominant Markers: A Bayesian Perspective , 2008, Genetics.

[155]  Kevin R. Thornton,et al.  A New Approach for Using Genome Scans to Detect Recent Positive Selection in the Human Genome , 2007, PLoS biology.

[156]  R. Lewontin,et al.  The Genetic Basis of Evolutionary Change , 2022 .

[157]  A. Fujimoto,et al.  A Practical Genome Scan for Population-Specific Strong Selective Sweeps That Have Reached Fixation , 2007, PloS one.

[158]  M. Nei,et al.  Concerted and birth-and-death evolution of multigene families. , 2005, Annual review of genetics.

[159]  B. Clarke,et al.  Selective Constraints on Amino-acid Substitutions during the Evolution of Proteins , 1970, Nature.

[160]  N. Morton,et al.  MEASUREMENT OF GENE FREQUENCY DRIFT IN SMALL POPULATIONS , 1955 .

[161]  J. B. S. Haldane,et al.  The cost of natural selection , 1957, Journal of Genetics.

[162]  M. Kreitman,et al.  Methods to detect selection in populations with applications to the human. , 2000, Annual review of genomics and human genetics.

[163]  S. Wright,et al.  The Distribution of Gene Frequencies Under Irreversible Mutation. , 1938, Proceedings of the National Academy of Sciences of the United States of America.

[164]  Hugues Roest Crollius,et al.  Human and Non-Human Primate Genomes Share Hotspots of Positive Selection , 2010, PLoS genetics.

[165]  J. L. King,et al.  Non-Darwinian evolution. , 1969, Science.

[166]  Or Zuk,et al.  A Composite of Multiple Signals Distinguishes Causal Variants in Regions of Positive Selection , 2010, Science.

[167]  R A Fisher,et al.  The spread of a gene in natural conditions in a colony of the moth Panaxia dominula L. , 1947, Heredity.

[168]  J. Crow Darwinian and non-Darwinian evolution , 1972 .

[169]  R. Nielsen,et al.  Patterns of Positive Selection in Six Mammalian Genomes , 2008, PLoS genetics.

[170]  Pardis C Sabeti,et al.  Detecting recent positive selection in the human genome from haplotype structure , 2002, Nature.

[171]  Molly Przeworski,et al.  How reliable are empirical genomic scans for selective sweeps? , 2006, Genome research.

[172]  M. O. Dayhoff,et al.  Atlas of protein sequence and structure , 1965 .

[173]  M. Kimura The Neutral Theory of Molecular Evolution: Introduction , 1983 .

[174]  A. Hughes Near Neutrality , 2008, Annals of the New York Academy of Sciences.

[175]  E. Jacobs,et al.  The reversible removal of cytochrome c from mitochondria. , 1960, The Journal of biological chemistry.

[176]  L. Buck,et al.  Combinatorial Receptor Codes for Odors , 1999, Cell.

[177]  M. Nei,et al.  A new method of inference of ancestral nucleotide and amino acid sequences. , 1995, Genetics.