INVITED REVIEW: Using genome scans of DNA polymorphism to infer adaptive population divergence

Elucidating the genetic basis of adaptive population divergence is a goal of central importance in evolutionary biology. In principle, it should be possible to identify chromosomal regions involved in adaptive divergence by screening genome‐wide patterns of DNA polymorphism to detect the locus‐specific signature of positive directional selection. In the case of spatially separated populations that inhabit different environments or sympatric populations that exploit different ecological niches, it is possible to identify loci that underlie divergently selected traits by comparing relative levels of differentiation among large numbers of unlinked markers. In this review I first address the question of whether diversifying selection on polygenic traits can be expected to produce predictable patterns of allelic variation at the underlying quantitative trait loci (QTL), and whether the locus‐specific effects of selection can be reliably detected against the genome‐wide backdrop of stochastic variability. I then review different approaches that have been developed to identify loci involved in adaptive population divergence and I discuss the relative merits of model‐based approaches that rely on assumptions about population structure vs. model‐free approaches that are based on empirical distributions of summary statistics. Finally, I consider the evolutionary and functional insights that might be gained by conducting genome scans for loci involved in adaptive population divergence.

[1]  Nicholas H. Barton,et al.  The Effects of Genetic and Geographic Structure on Neutral Variation , 2003 .

[2]  C. Krimbas,et al.  Testing the heterogeneity of F values: a suggestion and a correction. , 1976, Genetics.

[3]  B. Charlesworth,et al.  The effect of deleterious mutations on neutral molecular variation. , 1993, Genetics.

[4]  M. Nachman,et al.  Estimate of the mutation rate per nucleotide in humans. , 2000, Genetics.

[5]  D. Falconer,et al.  Introduction to Quantitative Genetics. , 1962 .

[6]  T. Wiehe The effect of selective sweeps on the variance of the allele distribution of a linked multiallele locus: hitchhiking of microsatellites. , 1998, Theoretical population biology.

[7]  V. Le Corre,et al.  Genetic variability at neutral markers, quantitative trait land trait in a subdivided population under selection. , 2003, Genetics.

[8]  W. Stephan,et al.  Detecting a local signature of genetic hitchhiking along a recombining chromosome. , 2002, Genetics.

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

[10]  R. Latta Differentiation of Allelic Frequencies at Quantitative Trait Loci Affecting Locally Adaptive Traits , 1998, The American Naturalist.

[11]  Mark A. Beaumont,et al.  TESTING FOR GENETIC EVIDENCE OF POPULATION EXPANSION AND CONTRACTION: AN EMPIRICAL ANALYSIS OF MICROSATELLITE DNA VARIATION USING A HIERARCHICAL BAYESIAN MODEL , 2002, Evolution; international journal of organic evolution.

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

[13]  S. Wright Evolution in mendelian populations , 1931 .

[14]  P. Newton,et al.  A selective sweep driven by pyrimethamine treatment in southeast asian malaria parasites. , 2003, Molecular biology and evolution.

[15]  Christian Schlötterer,et al.  Allele excess at neutrally evolving microsatellites and the implications for tests of neutrality , 2004, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[16]  M. Nei,et al.  Mathematical model for studying genetic variation in terms of restriction endonucleases. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Nachman,et al.  Genome scans of DNA variability in humans reveal evidence for selective sweeps outside of Africa. , 2004, Molecular biology and evolution.

[18]  Wandering distributions and the electrophoretic profile. , 1975, Theoretical population biology.

[19]  Insecticide resistance in the mosquito Culex pipiens: What have we learned about adaptation? , 2001 .

[20]  Christian Schlötterer,et al.  A microsatellite-based multilocus screen for the identification of local selective sweeps. , 2002, Genetics.

[21]  Mark D Shriver,et al.  The genomic distribution of population substructure in four populations using 8,525 autosomal SNPs , 2004, Human Genomics.

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

[23]  J. M. Smith,et al.  The hitch-hiking effect of a favourable gene. , 1974, Genetical research.

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

[25]  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.

[26]  Noah A. Rosenberg,et al.  Genealogical trees, coalescent theory and the analysis of genetic polymorphisms , 2002, Nature Reviews Genetics.

[27]  B. Charlesworth,et al.  The effects of local selection, balanced polymorphism and background selection on equilibrium patterns of genetic diversity in subdivided populations. , 1997, Genetical research.

[28]  T. Anderson Mapping drug resistance genes in Plasmodium falciparum by genome-wide association. , 2004, Current drug targets. Infectious disorders.

[29]  W Stephan,et al.  The hitchhiking effect on the site frequency spectrum of DNA polymorphisms. , 1995, Genetics.

[30]  G. Partridge Relative fitness of genotypes in a population of Rattus norvegicus polymorphic for warfarin resistance , 1979, Heredity.

[31]  K. Houchins,et al.  Identifying genes of agronomic importance in maize by screening microsatellites for evidence of selection during domestication , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[32]  T. Mitchell-Olds Faculty Opinions recommendation of Population genetic and phylogenetic evidence for positive selection on regulatory mutations at the factor VII locus in humans. , 2005 .

[33]  R. Wayne,et al.  Natural selection mapping of the warfarin-resistance gene. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[34]  N. Barton Clines in polygenic traits. , 1999, Genetical research.

[35]  M. Stoneking,et al.  A genome scan to detect candidate regions influenced by local natural selection in human populations. , 2003, Molecular biology and evolution.

[36]  P. Moran Wandering distributions and the electrophoretic profile. , 1975, Theoretical population biology.

[37]  B. Charlesworth,et al.  The pattern of neutral molecular variation under the background selection model. , 1995, Genetics.

[38]  M. Nei,et al.  Molecular Evolution and Phylogenetics , 2000 .

[39]  T. Wiehe,et al.  Microsatellites, a neutral marker to infer selective sweeps , 1999 .

[40]  A. Di Rienzo,et al.  Detection of the signature of natural selection in humans: evidence from the Duffy blood group locus. , 2000, American journal of human genetics.

[41]  A. Long,et al.  Genetic interactions between naturally occurring alleles at quantitative trait loci and mutant alleles at candidate loci affecting bristle number in Drosophila melanogaster. , 1996, Genetics.

[42]  R. Latta Gene flow, adaptive population divergence and comparative population structure across loci , 2003 .

[43]  W. G. Hill,et al.  The effect of linkage on limits to artificial selection. , 1966, Genetical research.

[44]  W. Li,et al.  Statistical tests of neutrality of mutations. , 1993, Genetics.

[45]  T. Mackay,et al.  Linkage disequilibrium mapping of molecular polymorphisms at the scabrous locus associated with naturally occurring variation in bristle number in Drosophila melanogaster. , 1999, Genetical research.

[46]  C. Schlötterer,et al.  A microsatellite variability screen for positive selection associated with the "out of Africa" habitat expansion of Drosophila melanogaster. , 2003, Genetics.

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

[48]  A. Long,et al.  Both naturally occurring insertions of transposable elements and intermediate frequency polymorphisms at the achaete-scute complex are associated with variation in bristle number in Drosophila melanogaster. , 2000, Genetics.

[49]  S. Wright,et al.  Genetical Structure of Populations , 1950, Nature.

[50]  N L Kaplan,et al.  Deleterious background selection with recombination. , 1995, Genetics.

[51]  Molly Przeworski,et al.  The signature of positive selection at randomly chosen loci. , 2002, Genetics.

[52]  Thomas Wiehe,et al.  The Effect of Strongly Selected Substitutions on Neutral Polymorphism: Analytical Results Based on Diffusion Theory , 1992 .

[53]  K. Holsinger The neutral theory of molecular evolution , 2004 .

[54]  W. Stephan,et al.  Joint effects of genetic hitchhiking and background selection on neutral variation. , 2000, Genetics.

[55]  D. Petry,et al.  The effect on neutral gene flow of selection at a linked locus. , 1983, Theoretical population biology.

[56]  L. Cavalli-Sforza Population structure and human evolution , 1966, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[57]  G. Ledyard Stebbins,et al.  The Major Features of Evolution . George Gaylord Simpson. Columbia Univ. Press, New York, 1953. 434 pp. Illus. $7.50 , 1954, Science.

[58]  C. Baer,et al.  Population genomics: genome-wide sampling of insect populations. , 2001, Annual review of entomology.

[59]  M. Kreitman,et al.  A Population Genetic Test of Selection at the Molecular Level , 1995, Science.

[60]  D. F. Roberts,et al.  The History and Geography of Human Genes , 1996 .

[61]  C. Schlötterer Evolutionary dynamics of microsatellite DNA , 2000, Chromosoma.

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

[63]  T. Mackay,et al.  Molecular and phenotypic variation in the achaete-scute region of Drosophila melanogaster , 1990, Nature.

[64]  C. Schlötterer,et al.  Patterns of microsatellite variability among X chromosomes and autosomes indicate a high frequency of beneficial mutations in non-African D. simulans. , 2004, Molecular biology and evolution.

[65]  D. A. Kirby,et al.  A test of the background selection hypothesis based on nucleotide data from Drosophila ananassae. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[66]  John C. Wootton,et al.  Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum , 2002, Nature.

[67]  J. Gillespie The causes of molecular evolution , 1991 .

[68]  N. Barton,et al.  The barrier to genetic exchange between hybridising populations , 1986, Heredity.

[69]  C. Aquadro,et al.  Evolution at the tip and base of the X chromosome in an African population of Drosophila melanogaster. , 1995, Molecular biology and evolution.

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

[71]  H. A. Orr,et al.  The evolutionary genetics of adaptation: a simulation study. , 1999, Genetical research.

[72]  M. Raymond,et al.  Insecticide resistance in the mosquito Culex pipiens: what have we learned about adaptation? , 2004, Genetica.

[73]  K. Kidd,et al.  Geographic and haplotype structure of candidate type 2 diabetes susceptibility variants at the calpain-10 locus. , 2002, American journal of human genetics.

[74]  B. Charlesworth Measures of divergence between populations and the effect of forces that reduce variability. , 1998, Molecular biology and evolution.

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

[76]  R. Butlin,et al.  Differential gene exchange between parapatric morphs of Littorina saxatilis detected using AFLP markers , 2001 .

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

[78]  A. Di Rienzo,et al.  Complex signatures of natural selection at the Duffy blood group locus. , 2002, American journal of human genetics.

[79]  J. Hey,et al.  USING HITCHHIKING GENES TO STUDY ADAPTATION AND DIVERGENCE DURING SPECIATION WITHIN THE DROSOPHILA MELANOGASTER SPECIES COMPLEX , 1994, Evolution; international journal of organic evolution.

[80]  G. Turner The Ecology of Adaptive Radiation , 2001, Heredity.

[81]  NATURAL SELECTION ON PROTEIN POLYMORPHISM IN THE RODENT GENUS PEROMYSCUS: EVIDENCE FROM INTERLOCUS CONTRASTS , 2003, Evolution; international journal of organic evolution.

[82]  C. Aquadro,et al.  African and North American populations of Drosophila melanogaster are very different at the DNA level , 1993, Nature.

[83]  Alberto Piazza,et al.  The History and Geography of Human Genes: Abridged paperback Edition , 1996 .

[84]  R. Lande The response to selection on major and minor mutations affecting a metrical trait , 1983, Heredity.

[85]  M. Slatkin Inbreeding coefficients and coalescence times. , 2007, Genetical research.

[86]  L. Bernatchez,et al.  Generic scan using AFLP markers as a means to assess the role of directional selection in the divergence of sympatric whitefish ecotypes. , 2004, Molecular biology and evolution.

[87]  R. Punnett,et al.  The Genetical Theory of Natural Selection , 1930, Nature.

[88]  H. A. Orr,et al.  THE POPULATION GENETICS OF ADAPTATION: THE DISTRIBUTION OF FACTORS FIXED DURING ADAPTIVE EVOLUTION , 1998, Evolution; international journal of organic evolution.

[89]  A. Long,et al.  Naturally occurring variation in bristle number and DNA polymorphisms at the scabrous locus of Drosophila melanogaster. , 1994, Science.

[90]  D. Balding,et al.  Identifying adaptive genetic divergence among populations from genome scans , 2004, Molecular ecology.

[91]  N L Kaplan,et al.  The "hitchhiking effect" revisited. , 1989, Genetics.

[92]  N. Barton,et al.  Genetic hitchhiking. , 2000, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[93]  S. Wright,et al.  Isolation by Distance. , 1943, Genetics.

[94]  S. Williamson,et al.  The genealogy of a sequence subject to purifying selection at multiple sites. , 2002, Molecular biology and evolution.

[95]  H. A. Orr,et al.  The Genetics of Adaptation: A Reassessment , 1992, The American Naturalist.

[96]  M. Nachman,et al.  NATURAL SELECTION ON PROTEIN POLYMORPHISM IN THE RODENT GENUS PEROMYSCUS: EVIDENCE FROM INTERLOCUS CONTRASTS , 2003, Evolution; international journal of organic evolution.

[97]  R. French-Constant The molecular and population genetics of cyclodiene insecticide resistance. , 1994 .

[98]  R. ffrench-Constant,et al.  A Single P450 Allele Associated with Insecticide Resistance in Drosophila , 2002, Science.

[99]  K K Kidd,et al.  Drift, admixture, and selection in human evolution: a study with DNA polymorphisms. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[100]  Justin C. Fay,et al.  Hitchhiking under positive Darwinian selection. , 2000, Genetics.

[101]  N. Takahata Genealogy of neutral genes and spreading of selected mutations in a geographically structured population. , 1991, Genetics.

[102]  D. Tautz,et al.  Polymorphism and locus-specific effects on polymorphism at microsatellite loci in natural Drosophila melanogaster populations. , 1997, Genetics.

[103]  J. McDonald Detecting Natural Selection by Comparing Geographic Variation in Protein and DNA Polymorphisms , 1994 .

[104]  M Kimmel,et al.  Signatures of population expansion in microsatellite repeat data. , 1998, Genetics.

[105]  R. Lewontin Detecting Population Differences in Quantitative Characters as Opposed to Gene Frequencies , 1984, The American Naturalist.

[106]  N. Barton Linkage and the limits to natural selection. , 1995, Genetics.

[107]  T. Ohta,et al.  Linkage disequilibrium due to random genetic drift in finite subdivided populations. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[108]  P. Taberlet,et al.  The power and promise of population genomics: from genotyping to genome typing , 2003, Nature Reviews Genetics.

[109]  M. Slatkin Hitchhiking and associative overdominance at a microsatellite locus. , 1995, Molecular biology and evolution.

[110]  C. Schlötterer,et al.  Hitchhiking mapping: A population-based fine-mapping strategy for adaptive mutations in Drosophila melanogaster , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[111]  R. Hudson,et al.  A statistical test for detecting geographic subdivision. , 1992, Molecular biology and evolution.

[112]  Matthew W. Hahn,et al.  Positive Selection on a Human-Specific Transcription Factor Binding Site Regulating IL4 Expression , 2003, Current Biology.

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

[114]  C. Fenster,et al.  Quantitative trait locus analyses and the study of evolutionary process , 2004, Molecular ecology.

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

[116]  S. Leal Genetics and Analysis of Quantitative Traits , 2001 .

[117]  H. Tachida Molecular Evolution in a Multisite Nearly Neutral Mutation Model , 2000, Journal of Molecular Evolution.

[118]  G. Churchill,et al.  Properties of statistical tests of neutrality for DNA polymorphism data. , 1995, Genetics.

[119]  W. Stephan Effects of Genetic Recombination and Population Subdivision on Nucleotide Sequence Variation in Drosophila ananassae , 1994 .

[120]  W. Stephan,et al.  Analysis of a genetic hitchhiking model, and its application to DNA polymorphism data from Drosophila melanogaster. , 1993, Molecular biology and evolution.

[121]  C. Schlötterer,et al.  Chromosomal patterns of microsatellite variability contrast sharply in African and non-African populations of Drosophila melanogaster. , 2002, Genetics.

[122]  Motoo Kimura,et al.  A model of mutation appropriate to estimate the number of electrophoretically detectable alleles in a finite population*. , 1973, Genetical research.

[123]  M. Bamshad,et al.  A strong signature of balancing selection in the 5′ cis-regulatory region of CCR5 , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[124]  P. Andolfatto Adaptive hitchhiking effects on genome variability. , 2001, Current opinion in genetics & development.

[125]  J. Dubach,et al.  NATURAL SELECTION DRIVES ALTITUDINAL DIVERGENCE AT THE ALBUMIN LOCUS IN DEER MICE, PEROMYSCUS MANICULATUS , 2004, Evolution; international journal of organic evolution.

[126]  John Maynard Smith,et al.  The hitch-hiking effect of a favourable gene. , 1974, Genetical research.

[127]  R. Wayne,et al.  Locus-specific genetic differentiation at Rw among warfarin-resistant rat (Rattus norvegicus) populations. , 2003, Genetics.

[128]  T. Mackay,et al.  Low mutation rates of microsatellite loci in Drosophila melanogaster , 1997, Nature Genetics.

[129]  R. ffrench-Constant The molecular and population genetics of cyclodiene insecticide resistance. , 1994, Insect biochemistry and molecular biology.

[130]  Jonathan Flint,et al.  Finding the molecular basis of quatitative traits: successes and pitfalls , 2001, Nature Reviews Genetics.

[131]  R. Lande NEUTRAL THEORY OF QUANTITATIVE GENETIC VARIANCE IN AN ISLAND MODEL WITH LOCAL EXTINCTION AND COLONIZATION , 1992, Evolution; international journal of organic evolution.

[132]  B. Charlesworth,et al.  Muller's ratchet and the pattern of variation at a neutral locus. , 2002, Genetics.

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

[134]  M. Nachman,et al.  Searching for evidence of positive selection in the human genome using patterns of microsatellite variability. , 2002, Molecular biology and evolution.

[135]  C. Schlötterer Hitchhiking mapping--functional genomics from the population genetics perspective. , 2003, Trends in genetics : TIG.

[136]  H. Ellegren Microsatellite mutations in the germline: implications for evolutionary inference. , 2000, Trends in genetics : TIG.

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

[138]  J. McKay,et al.  Adaptive population divergence: markers, QTL and traits , 2002 .