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Demography-adjusted tests of neutrality based on genome-wide SNP data.

M Rafajlović1, A Klassmann2, A Eriksson3

  • 1Department of Physics, University of Gothenburg, SE-412 96 Gothenburg, Sweden; The Linnaeus Centre for Marine Evolutionary Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden.

Theoretical Population Biology
|June 10, 2014
PubMed
Summary

This study extends neutral evolution tests to account for changing population sizes, crucial for accurate human population comparisons. Demography-adjusted tests reveal that population history explains most observed differences, aiding in identifying positive selection.

Keywords:
BottleneckCoalescent approximationInfinite-sites modelSingle nucleotide polymorphismSite frequency spectrum (SFS)

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Area of Science:

  • Population genetics
  • Evolutionary biology
  • Genomics

Background:

  • Neutral evolution hypothesis testing typically assumes constant population size.
  • The impact of fluctuating population sizes on these tests is not well understood.
  • Existing methods for analyzing the site frequency spectrum may be confounded by demographic history.

Purpose of the Study:

  • To extend existing frameworks for neutral evolution tests to incorporate varying population sizes.
  • To develop demography-adjusted statistical tests for detecting natural selection.
  • To analyze human population genetic data and identify regions under recent positive selection.

Main Methods:

  • Extended the Achaz and Ferretti framework for site frequency spectrum tests to include population size changes.
  • Developed analytical methods to compute the first two moments of the site frequency spectrum for populations with two instantaneous size changes.
  • Applied demography-adjusted versions of Tajima's D, Fay & Wu's H, and Zeng's E to human population data from the 1000 Genomes Project.

Main Results:

  • Demography-adjusted test statistics enable direct comparison of selection signals across human populations.
  • The majority of inter-population differences in neutrality tests are attributable to demographic history.
  • Identified candidate genomic regions exhibiting signals of recent positive selection after accounting for demography.

Conclusions:

  • Accounting for population size changes is essential for robust neutral evolution hypothesis testing.
  • Demographic history significantly influences population genetic test statistics.
  • The developed methods and adjusted statistics are valuable tools for identifying recent positive selection in human populations.