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Modeling Human Population Separation History Using Physically Phased Genomes.

Shiya Song1, Elzbieta Sliwerska2, Sarah Emery2

  • 1Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, Michigan 48109.

Genetics
|January 5, 2017
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Summary
This summary is machine-generated.

Experimentally phased haplotypes provide more accurate human population history insights than statistical phasing. This study used fosmid pool sequencing to resolve phased haplotypes, revealing crucial details about population splits and gene flow.

Keywords:
MSMCPSMCapproximate Bayesian computationfosmid pool sequencinghaplotypepopulation split time

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Area of Science:

  • Population Genetics
  • Human Evolutionary Studies
  • Genomics

Background:

  • Haplotype phase is critical for understanding human population genetics, reflecting recombination, selection, and population size changes.
  • Current methods often rely on statistical phasing of unphased data, which may introduce inaccuracies.
  • Accurate haplotype phasing is essential for reliable inference of population history.

Purpose of the Study:

  • To evaluate the impact of correct haplotype phase on population history inference.
  • To compare population history estimates derived from statistically phased versus experimentally phased haplotypes.
  • To refine models of human population divergence and gene flow using high-resolution phased haplotypes.

Main Methods:

  • Fosmid pool sequencing was employed to generate physically phased haplotypes for individuals from diverse African populations.
  • High-throughput sequencing data was processed to resolve phased haplotypes across large genomic blocks (N50 of 1 Mbp).
  • Pairwise and multiple sequentially Markovian coalescent models, alongside approximate Bayesian computation, were used to analyze population split times and migration rates.

Main Results:

  • Experimentally phased haplotypes yielded more accurate estimations of population split times compared to statistically phased haplotypes.
  • The study inferred separation between hunter-gatherer and other populations around 120-140 KYA, with ongoing gene flow until 30-40 KYA.
  • Separation times were estimated for West African and out-of-Africa populations (~70-80 KYA) and Maasai and out-of-Africa populations (~50 KYA).

Conclusions:

  • Accurate haplotype phasing is crucial for robust inference of human population history and evolutionary dynamics.
  • Experimentally phased haplotypes offer a more reliable basis for demographic modeling than statistical phasing methods.
  • The findings provide refined estimates for key divergence events and gene flow patterns in human evolutionary history.