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bioRxiv · 10.1101/2024.11.26.625554

Divergent reference genomes compromise the reconstruction of demographic histories, selection scans, and population genetic summary statistics

Akopyan, M.·Genchev, M.·Armstrong, E. E.·Mooney, J. A.
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Abstract

Characterizing genetic variation in natural populations is vital to evolutionary biology, however many non-model species lack genomic resources. Here, we demonstrate that reference bias significantly affects population genomic analyses by mapping whole genome sequence data from gray foxes (Urocyon cinereoargenteus) to a conspecific reference and two heterospecific canid genomes (dog and Arctic fox). Mapping to the conspecific genome improved read pairing by [~]5%, detected 26-32% more SNPs, and 33-35% more singletons. Nucleotide diversity estimates increased over 30%, FST increased from 0.189 to 0.197, and effective population size estimates were 30-60% higher with the conspecific reference. Recombination rates varied by up to 3-fold at chromosome ends with heterospecific references. Importantly, FST outlier detection differed markedly, with heterospecific genomes identifying twice as many unique outlier windows. These findings highlight the impact of reference genome choice and the importance of conspecific genomic resources for accurate evolutionary inference. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/625554v2_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@1d717adorg.highwire.dtl.DTLVardef@537c85org.highwire.dtl.DTLVardef@1142d10org.highwire.dtl.DTLVardef@19a9f06_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIA species-specific reference genome improves read mapping and variant detection C_LIO_LIReference bias underestimates genetic diversity and differentiation C_LIO_LIDivergent reference genomes distort demographic histories and recombination landscapes C_LIO_LIUnique FST outliers are detected across references, affecting functional interpretations C_LI

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Akopyan, M., Genchev, M., Armstrong, E. E., Mooney, J. A.. 2024-11-30. Divergent reference genomes compromise the reconstruction of demographic histories, selection scans, and population genetic summary statistics. https://doi.org/10.1101/2024.11.26.625554

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