A high coverage Mesolithic aurochs genome and effective leveraging of ancient cattle genomes using whole genome imputation

Abstract

21 Ancient genomic analyses are often restricted to utilising pseudo-haploid data due to low 22 genome coverage. Leveraging low coverage data by imputation to calculate phased diploid 23 genotypes that enable haplotype-based interrogation and SNP calling at unsequenced 24 positions is highly desirable. This has not been investigated for ancient cattle genomes despite 25 these being compelling subjects for archaeological, evolutionary and economic reasons. Here 26 we test this approach by sequencing a Mesolithic European aurochs (18.49x; 9852-9376 27 calBC), an Early Medieval European cow (18.69x; 427-580 calAD), and combine these with 28 published individuals; two ancient and three modern. We downsample these genomes (0.25x, 29 0.5x, 1.0x, 2.0x) and impute diploid genotypes, utilising a reference panel of 171 published 30 modern cattle genomes that we curated for 21.7 million (Mn) phased single-nucleotide 1 bioRxiv preprint doi: https://doi.org/10.1101/2024.01.23.576850; this version posted January 24, 2024. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. 31 polymorphisms (SNPs). We recover high densities of correct calls with an accuracy of >99.1% 32 at variant sites for the lowest downsample depth of 0.25x, increasing to >99.5% for 2.0x 33 (transversions only, minor allele frequency (MAF) ≥2.5%). The recovery of SNPs correlates 34 with coverage, on average 58% of sites are recovered for 0.25x increasing to 87% for 2.0x, 35 utilising an average of 3.5 million (Mn) transversions (MAF ≥2.5%), even in the aurochs which 36 is temporally and morphologically distinct from the reference panel. Our imputed genomes 37 behave similarly to directly called data in allele-frequency-based analyses; for example 38 consistently identifying runs of homozygosity >2mb, including a long homozygous region in 39 the Mesolithic European aurochs. 40 41