Originally published as Genetics Published Articles Ahead of Print on May 23, 2005.

Genetics, Vol. 170, 1401-1410, July 2005, Copyright © 2005
doi:10.1534/genetics.104.038224

Distinguishing Between Selective Sweeps and Demography Using DNA Polymorphism Data

Jeffrey D. Jensen*, Yuseob Kim{dagger},1, Vanessa Bauer DuMont*, Charles F. Aquadro*,2 and Carlos D. Bustamante{dagger}

* Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853
{dagger} Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853

2 Corresponding author: Department of Molecular Biology and Genetics, 235 Biotechnology Bldg., Cornell University, Ithaca, NY 14850.
E-mail: cfa1{at}cornell.edu

In 2002 Kim and Stephan proposed a promising composite-likelihood method for localizing and estimating the fitness advantage of a recently fixed beneficial mutation. Here, we demonstrate that their composite-likelihood-ratio (CLR) test comparing selective and neutral hypotheses is not robust to undetected population structure or a recent bottleneck, with some parameter combinations resulting in a false positive rate of nearly 90%. We also propose a goodness-of-fit test for discriminating rejections due to directional selection (true positive) from those due to population and demographic forces (false positives) and demonstrate that the new method has high sensitivity to differentiate the two classes of rejections.




This article has been cited by other articles:


Home page
 Mol Biol EvolHome page
N. Svetec, P. Pavlidis, and W. Stephan
Recent Strong Positive Selection on Drosophila melanogaster HDAC6, a Gene Encoding a Stress Surveillance Factor, as Revealed by Population Genomic Analysis
Mol. Biol. Evol., July 1, 2009; 26(7): 1549 - 1556.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
F. Tian, N. M. Stevens, and E. S. Buckler IV
In the Light of Evolution III: Two Centuries of Darwin Sackler Colloquium: Tracking footprints of maize domestication and evidence for a massive selective sweep on chromosome 10
PNAS, June 16, 2009; 106(Supplement_1): 9979 - 9986.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
K. E. Lohmueller, C. D. Bustamante, and A. G. Clark
Methods for Human Demographic Inference Using Haplotype Patterns From Genomewide Single-Nucleotide Polymorphism Data
Genetics, May 1, 2009; 182(1): 217 - 231.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
S. Boitard, C. Schlotterer, and A. Futschik
Detecting Selective Sweeps: A New Approach Based on Hidden Markov Models
Genetics, April 1, 2009; 181(4): 1567 - 1578.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
J. E. Pool and R. Nielsen
Inference of Historical Changes in Migration Rate From the Lengths of Migrant Tracts
Genetics, February 1, 2009; 181(2): 711 - 719.
[Abstract] [Full Text] [PDF]

Home page
 Brief BioinformHome page
Y. Kim and T. Wiehe
Simulation of DNA sequence evolution under models of recent directional selection
Brief Bioinform, January 1, 2009; 10(1): 84 - 96.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
L.-M. Chevin, S. Billiard, and F. Hospital
Hitchhiking Both Ways: Effect of Two Interfering Selective Sweeps on Linked Neutral Variation
Genetics, September 1, 2008; 180(1): 301 - 316.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
D. Zivkovic and T. Wiehe
Second-Order Moments of Segregating Sites Under Variable Population Size
Genetics, September 1, 2008; 180(1): 341 - 357.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
A. Ramirez-Soriano, S. E. Ramos-Onsins, J. Rozas, F. Calafell, and A. Navarro
Statistical Power Analysis of Neutrality Tests Under Demographic Expansions, Contractions and Bottlenecks With Recombination
Genetics, May 1, 2008; 179(1): 555 - 567.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
J. Lu, Y. Fu, S. Kumar, Y. Shen, K. Zeng, A. Xu, R. Carthew, and C.-I Wu
Adaptive Evolution of Newly Emerged Micro-RNA Genes in Drosophila
Mol. Biol. Evol., May 1, 2008; 25(5): 929 - 938.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Beisswanger and W. Stephan
Evidence that strong positive selection drives neofunctionalization in the tandemly duplicated polyhomeotic genes in Drosophila
PNAS, April 8, 2008; 105(14): 5447 - 5452.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
A. Ojeda, L.-S. Huang, J. Ren, A. Angiolillo, I.-C. Cho, H. Soto, C. Lemus-Flores, S. M. Makuza, J. M. Folch, and M. Perez-Enciso
Selection in the Making: A Worldwide Survey of Haplotypic Diversity Around a Causative Mutation in Porcine IGF2
Genetics, March 1, 2008; 178(3): 1639 - 1652.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
A. Wong, M. C. Turchin, M. F. Wolfner, and C. F. Aquadro
Evidence for Positive Selection on Drosophila melanogaster Seminal Fluid Protease Homologs
Mol. Biol. Evol., March 1, 2008; 25(3): 497 - 506.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
J. D. Jensen, K. R. Thornton, and C. F. Aquadro
Inferring Selection in Partially Sequenced Regions
Mol. Biol. Evol., February 1, 2008; 25(2): 438 - 446.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
J. M. Macpherson, G. Sella, J. C. Davis, and D. A. Petrov
Genomewide Spatial Correspondence Between Nonsynonymous Divergence and Neutral Polymorphism Reveals Extensive Adaptation in Drosophila
Genetics, December 1, 2007; 177(4): 2083 - 2099.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
J. D. Jensen, V. L. Bauer DuMont, A. B. Ashmore, A. Gutierrez, and C. F. Aquadro
Patterns of Sequence Variability and Divergence at the diminutive Gene Region of Drosophila melanogaster: Complex Patterns Suggest an Ancestral Selective Sweep
Genetics, October 1, 2007; 177(2): 1071 - 1085.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
J. D. Jensen, K. R. Thornton, C. D. Bustamante, and C. F. Aquadro
On the Utility of Linkage Disequilibrium as a Statistic for Identifying Targets of Positive Selection in Nonequilibrium Populations
Genetics, August 1, 2007; 176(4): 2371 - 2379.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
K. Zeng, S. Shi, and C.-I Wu
Compound Tests for the Detection of Hitchhiking Under Positive Selection
Mol. Biol. Evol., August 1, 2007; 24(8): 1898 - 1908.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
K. Zeng, S. Mano, S. Shi, and C.-I Wu
Comparisons of Site- and Haplotype-Frequency Methods for Detecting Positive Selection
Mol. Biol. Evol., July 1, 2007; 24(7): 1562 - 1574.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Ross-Ibarra, P. L. Morrell, and B. S. Gaut
Colloquium Papers: Plant domestication, a unique opportunity to identify the genetic basis of adaptation
PNAS, May 15, 2007; 104(suppl_1): 8641 - 8648.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
D. J. Orengo and M. Aguade
Genome Scans of Variation and Adaptive Change: Extended Analysis of a Candidate Locus Close to the phantom Gene Region in Drosophila melanogaster
Mol. Biol. Evol., May 1, 2007; 24(5): 1122 - 1129.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
K. R. Thornton and J. D. Jensen
Controlling the False-Positive Rate in Multilocus Genome Scans for Selection
Genetics, February 1, 2007; 175(2): 737 - 750.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
T. Wiehe, V. Nolte, D. Zivkovic, and C. Schlotterer
Identification of Selective Sweeps Using a Dynamically Adjusted Number of Linked Microsatellites
Genetics, January 1, 2007; 175(1): 207 - 218.
[Abstract] [Full Text] [PDF]

Home page
 Crop Sci.Home page
A. M. Casa, S. E. Mitchell, J. D. Jensen, M. T. Hamblin, A. H. Paterson, C. F. Aquadro, and S. Kresovich
Evidence for a Selective Sweep on Chromosome 1 of Cultivated Sorghum
Crop Sci., November 1, 2006; 46(Supplement_1): S-27 - S-40.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
J. E. Pool and C. F. Aquadro
History and Structure of Sub-Saharan Populations of Drosophila melanogaster
Genetics, October 1, 2006; 174(2): 915 - 929.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
S. Glinka, D. De Lorenzo, and W. Stephan
Evidence of Gene Conversion Associated with a Selective Sweep in Drosophila melanogaster
Mol. Biol. Evol., October 1, 2006; 23(10): 1869 - 1878.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
K. M. Teshima, G. Coop, and M. Przeworski
How reliable are empirical genomic scans for selective sweeps?
Genome Res., June 1, 2006; 16(6): 702 - 712.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
J. E. Pool, V. B. DuMont, J. L. Mueller, and C. F. Aquadro
A Scan of Molecular Variation Leads to the Narrow Localization of a Selective Sweep Affecting Both Afrotropical and Cosmopolitan Populations of Drosophila melanogaster
Genetics, February 1, 2006; 172(2): 1093 - 1105.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
C. Schlotterer, H. Neumeier, C. Sousa, and V. Nolte
Highly Structured Asian Drosophila melanogaster Populations: A New Tool for Hitchhiking Mapping?
Genetics, January 1, 2006; 172(1): 287 - 292.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
S. Beisswanger, W. Stephan, and D. De Lorenzo
Evidence for a Selective Sweep in the wapl Region of Drosophila melanogaster
Genetics, January 1, 2006; 172(1): 265 - 274.
[Abstract] [Full Text] [PDF]

Home page
 Mol Biol EvolHome page
M. Soejima, H. Tachida, T. Ishida, A. Sano, and Y. Koda
Evidence for Recent Positive Selection at the Human AIM1 Locus in a European Population
Mol. Biol. Evol., January 1, 2006; 23(1): 179 - 188.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. F. Voight, A. M. Adams, L. A. Frisse, Y. Qian, R. R. Hudson, and A. Di Rienzo
Interrogating multiple aspects of variation in a full resequencing data set to infer human population size changes
PNAS, December 20, 2005; 102(51): 18508 - 18513.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
R. Nielsen, S. Williamson, Y. Kim, M. J. Hubisz, A. G. Clark, and C. Bustamante
Genomic scans for selective sweeps using SNP data
Genome Res., November 1, 2005; 15(11): 1566 - 1575.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
V. B. DuMont and C. F. Aquadro
Multiple Signatures of Positive Selection Downstream of Notch on the X Chromosome in Drosophila melanogaster
Genetics, October 1, 2005; 171(2): 639 - 653.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
L. Zhu and C. D. Bustamante
A Composite-Likelihood Approach for Detecting Directional Selection From DNA Sequence Data
Genetics, July 1, 2005; 170(3): 1411 - 1421.
[Abstract] [Full Text] [PDF]