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

Christian D. Huber, Michael DeGiorgio, Ines Hellmann, Rasmus Nielsen

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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 (along the chromosome) of the site frequency spectrum 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 adding fixed differences relative to an out-group to account for variation in mutation rate, thereby facilitating more robust and powerful analyses. We also develop a method for including background selection, modelled 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.

Original languageEnglish (US)
Pages (from-to)142-156
Number of pages15
JournalMolecular ecology
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Mutation Rate
mutation
genome
Genome
methodology
Mutation
effective population size
Population Density
chromosome
population size
Chromosomes
testing
rate
method
chromosomes
loci
simulation
test

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Genetics

Cite this

Huber, Christian D. ; DeGiorgio, Michael ; Hellmann, Ines ; Nielsen, Rasmus. / Detecting recent selective sweeps while controlling for mutation rate and background selection. In: Molecular ecology. 2016 ; Vol. 25, No. 1. pp. 142-156.
@article{af784dfe6a27479d8d6dc04755bb98d6,
title = "Detecting recent selective sweeps while controlling for mutation rate and background selection",
abstract = "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 (along the chromosome) of the site frequency spectrum 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-Aguad{\'e} test, we suggest adding fixed differences relative to an out-group to account for variation in mutation rate, thereby facilitating more robust and powerful analyses. We also develop a method for including background selection, modelled 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.",
author = "Huber, {Christian D.} and Michael DeGiorgio and Ines Hellmann and Rasmus Nielsen",
year = "2016",
month = "1",
day = "1",
doi = "10.1111/mec.13351",
language = "English (US)",
volume = "25",
pages = "142--156",
journal = "Molecular Ecology",
issn = "0962-1083",
publisher = "Wiley-Blackwell",
number = "1",

}

Detecting recent selective sweeps while controlling for mutation rate and background selection. / Huber, Christian D.; DeGiorgio, Michael; Hellmann, Ines; Nielsen, Rasmus.

In: Molecular ecology, Vol. 25, No. 1, 01.01.2016, p. 142-156.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Detecting recent selective sweeps while controlling for mutation rate and background selection

AU - Huber, Christian D.

AU - DeGiorgio, Michael

AU - Hellmann, Ines

AU - Nielsen, Rasmus

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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 (along the chromosome) of the site frequency spectrum 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 adding fixed differences relative to an out-group to account for variation in mutation rate, thereby facilitating more robust and powerful analyses. We also develop a method for including background selection, modelled 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.

AB - 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 (along the chromosome) of the site frequency spectrum 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 adding fixed differences relative to an out-group to account for variation in mutation rate, thereby facilitating more robust and powerful analyses. We also develop a method for including background selection, modelled 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.

UR - http://www.scopus.com/inward/record.url?scp=84954078351&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84954078351&partnerID=8YFLogxK

U2 - 10.1111/mec.13351

DO - 10.1111/mec.13351

M3 - Article

C2 - 26290347

AN - SCOPUS:84954078351

VL - 25

SP - 142

EP - 156

JO - Molecular Ecology

JF - Molecular Ecology

SN - 0962-1083

IS - 1

ER -