Detecting recent selective sweeps while controlling for mutation rate and background selection

A composite likelihood ratio test implemented in the program SweepFinder is a commonly used method for scanning a genome for recent selective sweeps. SweepFinder uses information on the spatial pattern of the site frequency spectrum (SFS) around the selected locus. To avoid confounding effects of background selection and variation in the mutation process along the genome, the method is typically applied only to sites that are variable within species. However, the power to detect and localize selective sweeps can be greatly improved if invariable sites are also included in the analysis. In the spirit of a Hudson-Kreitman-Aguadé test, we suggest to add fixed differences relative to an outgroup to account for variation in mutation rate, thereby facilitating more robust and powerful analyses. We also develop a method for including background selection modeled as a local reduction in the effective population size. Using simulations we show that these advances lead to a gain in power while maintaining robustness to mutation rate variation. Furthermore, the new method also provides more precise localization of the causative mutation than methods using the spatial pattern of segregating sites alone.

[1]  Michael DeGiorgio,et al.  SweepFinder2: increased sensitivity, robustness and flexibility , 2015, Bioinform..

[2]  Philipp W. Messer,et al.  Recent Selective Sweeps in North American Drosophila melanogaster Show Signatures of Soft Sweeps , 2013, PLoS genetics.

[3]  J. Hermisson,et al.  Keeping It Local: Evidence for Positive Selection in Swedish Arabidopsis thaliana , 2014, Molecular biology and evolution.

[4]  R. Nielsen,et al.  A Model-Based Approach for Identifying Signatures of Ancient Balancing Selection in Genetic Data , 2014, PLoS genetics.

[5]  Josep M. Comeron,et al.  Background Selection as Baseline for Nucleotide Variation across the Drosophila Genome , 2014, bioRxiv.

[6]  Mark George Thomas,et al.  Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y , 2014, Proceedings of the National Academy of Sciences.

[7]  R. Nielsen,et al.  On Detecting Incomplete Soft or Hard Selective Sweeps Using Haplotype Structure , 2014, Molecular biology and evolution.

[8]  J. Johnston,et al.  Signatures of selection in the Iberian honey bee (Apis mellifera iberiensis) revealed by a genome scan analysis of single nucleotide polymorphisms , 2013, Molecular ecology.

[9]  Jeffrey D. Jensen,et al.  The impact of equilibrium assumptions on tests of selection , 2013, Front. Genet..

[10]  Michael M. Desai,et al.  Distortions in Genealogies due to Purifying Selection and Recombination , 2013, Genetics.

[11]  I. Hellmann,et al.  Massive genomic variation and strong selection in Arabidopsis thaliana lines from Sweden , 2013, Nature Genetics.

[12]  Nikolaos S. Alachiotis,et al.  SweeD: Likelihood-Based Detection of Selective Sweeps in Thousands of Genomes , 2013, Molecular biology and evolution.

[13]  Philipp W. Messer,et al.  Frequent adaptation and the McDonald–Kreitman test , 2012, Proceedings of the National Academy of Sciences.

[14]  B. Payseur,et al.  Genomic signatures of selection at linked sites: unifying the disparity among species , 2013, Nature Reviews Genetics.

[15]  R. Schnabel,et al.  Detection of selective sweeps in cattle using genome-wide SNP data , 2012, BMC Genomics.

[16]  D. Gianola,et al.  A High Resolution Genome-Wide Scan for Significant Selective Sweeps: An Application to Pooled Sequence Data in Laying Chickens , 2012, PloS one.

[17]  Michael M. Desai,et al.  Distortions in genealogies due to purifying selection. , 2012, Molecular biology and evolution.

[18]  David G. Knowles,et al.  Fast Computation and Applications of Genome Mappability , 2012, PloS one.

[19]  Brian Charlesworth,et al.  The Effects of Deleterious Mutations on Evolution at Linked Sites , 2012, Genetics.

[20]  Anders Albrechtsen,et al.  Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome , 2011, PLoS genetics.

[21]  B. Charlesworth,et al.  The Joint Effects of Background Selection and Genetic Recombination on Local Gene Genealogies , 2011, Genetics.

[22]  A. Clark,et al.  Detecting Directional Selection in the Presence of Recent Admixture in African-Americans , 2011, Genetics.

[23]  Haipeng Li,et al.  A new test for detecting recent positive selection that is free from the confounding impacts of demography. , 2011, Molecular biology and evolution.

[24]  A. Gylfason,et al.  Fine-scale recombination rate differences between sexes, populations and individuals , 2010, Nature.

[25]  W. Stephan,et al.  Searching for Footprints of Positive Selection in Whole-Genome SNP Data From Nonequilibrium Populations , 2010, Genetics.

[26]  Gregory Ewing,et al.  MSMS: a coalescent simulation program including recombination, demographic structure and selection at a single locus , 2010, Bioinform..

[27]  J. M. Comeron,et al.  Local effects of limited recombination: historical perspective and consequences for population estimates of adaptive evolution. , 2010, The Journal of heredity.

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

[29]  Robert B. Hartlage,et al.  This PDF file includes: Materials and Methods , 2009 .

[30]  Xun Xu,et al.  Complete Resequencing of 40 Genomes Reveals Domestication Events and Genes in Silkworm (Bombyx) , 2009, Science.

[31]  K. Ozaki,et al.  Association of the Tag SNPs in the Human SKT Gene (KIAA1217) With Lumbar Disc Herniation , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

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

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

[34]  Christian Schlötterer,et al.  Detecting Selective Sweeps: A New Approach Based on Hidden Markov Models , 2009, Genetics.

[35]  Ryan D. Hernandez,et al.  A flexible forward simulator for populations subject to selection and demography , 2008, Bioinform..

[36]  W Stephan,et al.  A population genomic approach to map recent positive selection in model species , 2008, Molecular ecology.

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

[38]  Kevin R. Thornton,et al.  On the Utility of Linkage Disequilibrium as a Statistic for Identifying Targets of Positive Selection in Nonequilibrium Populations , 2007, Genetics.

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

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

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

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

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

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

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

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

[47]  Carlos Bustamante,et al.  Genomic scans for selective sweeps using SNP data. , 2005, Genome research.

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

[49]  C. Bustamante,et al.  Distinguishing Between Selective Sweeps and Demography Using DNA Polymorphism Data , 2005, Genetics.

[50]  Richard Durrett,et al.  Approximating selective sweeps. , 2004, Theoretical population biology.

[51]  R. Nielsen,et al.  Linkage Disequilibrium as a Signature of Selective Sweeps , 2004, Genetics.

[52]  Gabor T. Marth,et al.  The Allele Frequency Spectrum in Genome-Wide Human Variation Data Reveals Signals of Differential Demographic History in Three Large World Populations , 2004, Genetics.

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

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

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

[56]  Nicholas H. Barton,et al.  The effect of hitch-hiking on neutral genealogies , 1998 .

[57]  B. Charlesworth,et al.  The effect of recombination on background selection. , 1996, Genetical research.

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

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

[60]  R. Hudson,et al.  Gene Trees with Background Selection , 1994 .

[61]  Brian Golding,et al.  Non-Neutral Evolution , 1994, Springer US.

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

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

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

[65]  C. Counts.  Human genome sequencing. , 1986 .

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

[67]  H. Redkey,et al.  A new approach. , 1967, Rehabilitation record.

[68]  N. Clark,et al.  Direct Evidence , 1934 .