Human Population Differentiation Is Strongly Correlated with Local Recombination Rate

Allele frequency differences across populations can provide valuable information both for studying population structure and for identifying loci that have been targets of natural selection. Here, we examine the relationship between recombination rate and population differentiation in humans by analyzing two uniformly-ascertained, whole-genome data sets. We find that population differentiation as assessed by inter-continental F ST shows negative correlation with recombination rate, with F ST reduced by 10% in the tenth of the genome with the highest recombination rate compared with the tenth of the genome with the lowest recombination rate (P≪10−12). This pattern cannot be explained by the mutagenic properties of recombination and instead must reflect the impact of selection in the last 100,000 years since human continental populations split. The correlation between recombination rate and F ST has a qualitatively different relationship for F ST between African and non-African populations and for F ST between European and East Asian populations, suggesting varying levels or types of selection in different epochs of human history.

[1]  David Reich,et al.  Population differentiation as a test for selective sweeps. , 2010, Genome research.

[2]  Alkes L. Price,et al.  Reconstructing Indian Population History , 2009, Nature.

[3]  P. Green,et al.  Widespread Genomic Signatures of Natural Selection in Hominid Evolution , 2009, PLoS genetics.

[4]  Guy Sella,et al.  Pervasive Hitchhiking at Coding and Regulatory Sites in Humans , 2009, PLoS genetics.

[5]  J. Mullikin,et al.  Nature Genetics: doi:10.1038/ng.303Supplementary Methods , 2022 .

[6]  August E. Woerner,et al.  A novel DNA sequence database for analyzing human demographic history. , 2008, Genome research.

[7]  P. O’Reilly,et al.  Confounding between recombination and selection, and the Ped/Pop method for detecting selection. , 2008, Genome research.

[8]  R. Kulathinal,et al.  Fine-scale mapping of recombination rate in Drosophila refines its correlation to diversity and divergence , 2008, Proceedings of the National Academy of Sciences.

[9]  Francisco M. De La Vega,et al.  Population genetic analysis of shotgun assemblies of genomic sequences from multiple individuals. , 2008, Genome research.

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

[11]  M. Feldman,et al.  Worldwide Human Relationships Inferred from Genome-Wide Patterns of Variation , 2008 .

[12]  Ryan D. Hernandez,et al.  Proportionally more deleterious genetic variation in European than in African populations , 2008, Nature.

[13]  Zachary A. Szpiech,et al.  Genotype, haplotype and copy-number variation in worldwide human populations , 2008, Nature.

[14]  Jocelyn Kaiser,et al.  A Plan to Capture Human Diversity in 1000 Genomes , 2008, Science.

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

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

[17]  Pardis C Sabeti,et al.  Genome-wide detection and characterization of positive selection in human populations , 2007, Nature.

[18]  Zhaohui S. Qin,et al.  A second generation human haplotype map of over 3.1 million SNPs , 2007, Nature.

[19]  J. Mullikin,et al.  Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than in Europeans , 2007, Nature Genetics.

[20]  D. Charlesworth,et al.  Testing for Effects of Recombination Rate on Nucleotide Diversity in Natural Populations of Arabidopsis lyrata , 2006, Genetics.

[21]  Peter Donnelly,et al.  The Influence of Recombination on Human Genetic Diversity , 2006, PLoS genetics.

[22]  David Haussler,et al.  The UCSC Known Genes , 2006, Bioinform..

[23]  S. Tishkoff,et al.  Positive Selection Can Create False Hotspots of Recombination , 2006, Genetics.

[24]  R. Hudson,et al.  Interrogating multiple aspects of variation in a full resequencing data set to infer human population size changes. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

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

[26]  W. G. Hill,et al.  Measures of human population structure show heterogeneity among genomic regions. , 2005, Genome research.

[27]  P. Donnelly,et al.  A Fine-Scale Map of Recombination Rates and Hotspots Across the Human Genome , 2005, Science.

[28]  Hongkai Ji,et al.  Why do human diversity levels vary at a megabase scale? , 2005, Genome research.

[29]  Geoffrey B. Nilsen,et al.  Whole-Genome Patterns of Common DNA Variation in Three Human Populations , 2005, Science.

[30]  A. Caballero,et al.  Variation After a Selective Sweep in a Subdivided Population , 2005, Genetics.

[31]  M. Olivier.  A haplotype map of the human genome. , 2003, Nature.

[32]  M. Olivier.  A haplotype map of the human genome , 2003, Nature.

[33]  M. Hammer,et al.  Heterogeneous Patterns of Variation Among Multiple Human X-Linked Loci , 2004, Genetics.

[34]  Peter Donnelly,et al.  Application of Coalescent Methods to Reveal Fine-Scale Rate Variation and Recombination Hotspots , 2004, Genetics.

[35]  O. Tenaillon,et al.  Selection versus demography: a multilocus investigation of the domestication process in maize. , 2004, Molecular biology and evolution.

[36]  Alan David Hutson,et al.  Resampling Methods for Dependent Data , 2004, Technometrics.

[37]  P. Donnelly,et al.  The Fine-Scale Structure of Recombination Rate Variation in the Human Genome , 2004, Science.

[38]  Steven L Salzberg,et al.  Automated correction of genome sequence errors. , 2004, Nucleic acids research.

[39]  M. Stephens,et al.  Modeling linkage disequilibrium and identifying recombination hotspots using single-nucleotide polymorphism data. , 2003, Genetics.

[40]  G. McVean,et al.  Estimating recombination rates from population-genetic data , 2003, Nature Reviews Genetics.

[41]  S. Pääbo,et al.  A neutral explanation for the correlation of diversity with recombination rates in humans. , 2003, American journal of human genetics.

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

[43]  J. Wall,et al.  Testing models of selection and demography in Drosophila simulans. , 2002, Genetics.

[44]  Martin J Lercher,et al.  Human SNP variability and mutation rate are higher in regions of high recombination. , 2002, Trends in genetics : TIG.

[45]  R. Hudson,et al.  Inferences about human demography based on multilocus analyses of noncoding sequences. , 2002, Genetics.

[46]  D. Gudbjartsson,et al.  A high-resolution recombination map of the human genome , 2002, Nature Genetics.

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

[48]  S. P. Fodor,et al.  Blocks of Limited Haplotype Diversity Revealed by High-Resolution Scanning of Human Chromosome 21 , 2001, Science.

[49]  J. Wall,et al.  Gene conversion and different population histories may explain the contrast between polymorphism and linkage disequilibrium levels. , 2001, American journal of human genetics.

[50]  M. Nachman,et al.  Single nucleotide polymorphisms and recombination rate in humans. , 2001, Trends in genetics : TIG.

[51]  W. Stephan,et al.  Joint effects of natural selection and recombination on gene flow between Drosophila ananassae populations. , 2000, Genetics.

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

[53]  M. Nachman,et al.  DNA variability and recombination rates at X-linked loci in humans. , 1998, Genetics.

[54]  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.

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

[56]  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.

[57]  B. Charlesworth.  Background selection and patterns of genetic diversity in Drosophila melanogaster. , 1996, Genetical research.

[58]  B. Shafer,et al.  DNA synthesis errors associated with double-strand-break repair. , 1995, Genetics.

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

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

[61]  A. Pewsey.  Exploring the Limits of Bootstrap , 1994 .

[62]  W. Stephan,et al.  Reduced levels of DNA polymorphism and fixed between-population differences in the centromeric region of Drosophila ananassae. , 1992, Genetics.

[63]  C. Aquadro,et al.  Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster , 1992, Nature.

[64]  Regina Y. Liu.  Moving blocks jackknife and bootstrap capture weak dependence , 1992 .

[65]  H. Künsch.  The Jackknife and the Bootstrap for General Stationary Observations , 1989 .

[66]  Nicholas H. Barton,et al.  The Relative Rates of Evolution of Sex Chromosomes and Autosomes , 1987, The American Naturalist.

[67]  B. Weir,et al.  ESTIMATING F‐STATISTICS FOR THE ANALYSIS OF POPULATION STRUCTURE , 1984, Evolution; international journal of organic evolution.

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

[69]  R. Lewontin.  The Apportionment of Human Diversity , 1972 .

[70]  R. V. von Borstel,et al.  Different Rates of Spontaneous Mutation during Mitosis and Meiosis in Yeast. , 1962, Genetics.

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