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Reference genome choice compromises population genetic analyses.

Maria Akopyan1, Matthew Genchev2, Ellie E Armstrong3

  • 1Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA, USA; Department of Evolution, Ecology and Organismal Biology, University of California, Riverside, Riverside, CA, USA.

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|September 23, 2025
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Summary
This summary is machine-generated.

Choosing the right reference genome is crucial for accurate evolutionary studies. Using a gray fox conspecific reference improved genetic variation detection and estimates in population genomics research.

Keywords:
comparative genomicsconservationdemographic inferencepopulation geneticsrecombinationreference biasselection scan

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Area of Science:

  • Evolutionary Biology
  • Population Genomics
  • Genomic Resources

Background:

  • Characterizing genetic variation is vital for evolutionary biology.
  • Many non-model species lack essential genomic resources for population studies.

Purpose of the Study:

  • To investigate the impact of reference genome choice on population genomic analyses.
  • To assess how mapping to conspecific versus heterospecific genomes affects genetic variation detection and evolutionary inference in gray foxes.

Main Methods:

  • Whole-genome sequence data from gray foxes were mapped to conspecific (gray fox) and heterospecific (dog, Arctic fox) reference genomes.
  • Key population genomic metrics including SNP/singleton detection, nucleotide diversity, FST, effective population size, and recombination rates were analyzed.
  • The influence of reference choice on outlier detection for FST was evaluated.

Main Results:

  • Mapping to a conspecific reference improved read pairing by ~5% and detected significantly more SNPs and singletons.
  • Nucleotide diversity estimates increased by over 30%, and effective population size estimates were 30%-60% higher using the conspecific reference.
  • Recombination rates varied significantly with heterospecific references, and FST outlier detection differed markedly, with heterospecific genomes identifying twice as many unique outlier windows.

Conclusions:

  • Reference genome choice substantially impacts population genomic analyses and evolutionary inference.
  • The use of conspecific genomic resources is critical for accurate characterization of genetic variation and evolutionary processes.
  • Findings underscore the need for developing and utilizing species-specific genomic resources, especially for non-model organisms.