Imputation of ancient canid genomes reveals inbreeding history over the past 10,000 years.

Abstract

The multi-millennia-long history between dogs and humans has placed them at the forefront of archaeological and genomic research. Despite ongoing efforts including the analysis of ancient dog and wolf genomes, many questions remain regarding the evolutionary processes that led to the diversity of breeds today. Although ancient genome sequences provide valuable information about these processes, their utility is hindered by low depths of coverage and postmortem damage, which inhibits confident genotype calling. In the present study, we assess how genotype imputation of ancient dog and wolf genomes, using a large reference panel, can increase the amount of information provided by ancient datasets. We evaluated imputation accuracy by down-sampling high-coverage dog and wolf genomes to 0.05 to 2× coverage and compared concordance between imputed and high-coverage genotypes. We measured the impact of imputation on principal component analyses and runs of homozygosity (ROH). Our findings show high (R² > 0.9) imputation accuracy for dogs with coverage as low as 0.5× and for wolves as low as 1.0×. We then imputed a dataset of 90 ancient dog and wolf genomes to assess changes in inbreeding during the last 10,000 y of dog evolution. Ancient dog and wolf populations generally exhibit lower inbreeding levels than present-day individuals. Regions with low ROH density maintained across ancient and present-day dogs were significantly associated with genes related to immunity and chemosensory receptors. Our study indicates that imputing ancient canine genomes is a viable strategy that allows for the use of analytical methods previously limited to high-quality genetic data.